cysts (large follicles) and colloid in pituitary glands

GENERAL AND COMPARATIVE ENDOCRINOLOGY 45,425445 (1981)

REVIEW

Cysts (Large Follicles) and Colloid in Pituitary Glands

MICHAEL BENJAMIN

Department of Anatomy, University College, Cathays Park, Cardiff, Wales, United Kingdom

Accepted February 7, 1981

Cysts (G. kysdis) are bladders or sacs containing fluid, dead cells, or embryos. One cannot make any clear distinction between them and “follicles” and many authors use the terms interchangeably. Thus both must be discussed here. However, I shall mainly restrict myself to larger structures (~50 pm in diameter) where the size of the lumen greatly exceeds that of the surrounding cells. Pituitary “colloid” is an unfortunate term that is widely sanctioned by use. It refers to any material within the pituitary that resembles the colloid of the thyroid gland. It occurs in larger cavities such as cysts and the hypophysial cleft and as smaller droplets within and between cells. A remarkable number of authors have referred to cysts and colloid in pituitary glands. Yet it is difficult to compile a comprehensive bibliography, as neither the ti- tles nor the abstracts of many papers give any hint that such topics are mentioned.

Cysts and colloid were important to the older morphologists but are frequently ignored by modern authors. It is worth con- sidering why. The great German morphologists that dominated histology research before the First World War contrib- uted greatly to our early knowledge of cysts and colloid. Virchow compared the anterior lobe of the pituitary with the thyroid gland as he found similar colloid vesicles within it. Many lay great importance on this re- semblance and thought the two glands had similar functions and identical colloids that contained the “active principle” of the

glands. Herring (1915) was more cautious about the similarities of the colloids, particularly those in the pars nervosa. He was impressed by the blood pressor substances recently discovered in the pituitary, and thought the colloids contained them. Her- ring proposed that pars intermedia cells degenerate to produce colloid, either in the pars intermedia or in the pars nervosa. This colloid is carried by lymphatics to the third ventricle of the brain. Herring’s theory was expanded by others and was soon widely accepted. Colloid droplets in the pars nervosa were later renamed “Herring bodies.” Thus it was largely against the prevailing opinion of the time that Scharrer (1928) first proposed that colloid was produced in the hypothalamus and transported to the pars nervosa. The neurosecretory theory grew in stature and is of course widely held today. Our knowledge of colloids was greatly improved when Gomori’s chromic haematoxylin- phloxin was introduced as a way of discriminating between neurosecretory and other pituitary colloids.

Despite the popularity of the neurosecretory hypothesis, an interest in cysts and colloid was maintained after the Second World War by comparative morphologists. This era produced the classic works of Hanstrom (1946a,b, 1947, 1948, 1950, 1952a,b) and Wingstrand (195 1). Anyone interested in cysts and colloid should pay close attention to these papers. There are two main reasons why such topics were still taken seriously. First, the human pars in-

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426 MICHAEL BENJAMIN

termedia is polymorphic, rudimentary, and frequently cystic, and other animals have to be used for basic research. The pars intermedia seems to be commonly cystic in other animals. Second, before electron mi- croscopists demonstrated that secretory granules could be released from pituitary cells by exocytosis, the only morphological evidence for hormone release was the holocrine disintegration of cells, their apocrine ‘ ‘blebbing” and the stainable colloid.

Regrettably, it is no longer fashionable to study the comparative anatomy and histology of pituitary glands. Technical advances have turned our interests elsewhere-to the problem of what cells produce what hormones and more recently to how their secretion is controlled. Important problems of course, but ones that have largely led to the neglect of others. The main purpose of my review is to revive a little of the old interest in cysts and colloid, for there is much op- portunity for further study.

CYSTS (LARGE FOLLICLES)

A comprehensive, but not exhaustive, list of authors who have found pituitary cysts in a wide variety of vertebrates is given in Table 1. Cysts are best documented in man, as some have an important clinical significance that is briefly referred to later. It is especially with regard to man that the bibliography is incomplete, for there are a multitude of case reports, often dealing with only a single, postmortem finding, most of which cannot be considered in a general review such as this. Un- doubtedly the most detailed accounts of pituitary cysts are found in the monograph of Romeis (1940) and in the numerous papers of Hanstrom (see Table 1).

The Incidence of Cysts

Cysts may be naturally occurring or experimentally induced. They have been found in all major groups of vertebrates and are typical of dogs, chickens, and lampreys (Table 1). Estimates of cyst incidence vary

greatly between and within species. Ac- cording to Rao and Bhat (197 1) only 7% of dogs have cysts, whereas Rajan and Mohiyuddeen (1973) found them in 50% of animals. It is likely that the use of different breeds accounts for much of this discrep- ancy, as several authors have commented on the susceptibility of certain dogs to pituitary cysts (Oboussier, 1948; Anderson and Capen, 1978). German shepherd dogs are particularly vulnerable. Evidently cysts are common in birds and mammals in general, for Wingstrand (1951) and Hanstrom (see Table 1) often refer to them in their comparative studies.

Oboussier (1948) thinks cysts are more common in domestic species than in closely related wild forms. He found cysts in 57% of fowl pituitaries and 43% of domestic ducks, but did not find any in wild animals. Wingstrand (195 1) agrees that domestica- tion increases cyst incidence, but has also found cysts in wild birds. Hanstrom (1947, 1948, 1952a) comments a number of times on degenerative changes (including cysts) affecting the pars intermedia of captive or sick animals. Cysts form when vipers hibernate, are subjected to abnormal tem- peratures, or simply kept in captivity (Gabe and Saint Girons, 1960). Robertson and Wexler (1962) accentuated degenerative changes (including cyst formation) by keeping postspawning trout in captivity. When sticklebacks are starved or trans- ferred to seawater at certain times of the year, cysts form in the rostra1 pars distalis (see Benjamin, 1981 for references). Cysts have been recorded in several transplanted pituitaries-in the tree frog (Eakin, 1956)) the toad (Dongen et al., 1966), and the red eft (Masur, 1969).

Although cysts often characterise older animals (e.g., in man, Shanklin, 1951; mouse, Blumenthal, 1955; certain teleosts, Honma and Tamura, 1965; Yoshie and Honma, 1978), they are also present in young animals (chickens, Rahn, 1939; Wil- son, 1952; Legait, 1957; teleosts, Schreib-

CYSTS AND COLLOID IN PITUITARY GLANDS 427

TABLE 1 SOME REPORTED CASESOF PITUITARY CYSTS IN VARIOUS VERTEBRATES

Reference Species Position and/or type

of cyst

No. animals examined and/or

incidence

Kamer and Schreurs (1959)

Schreibman (1%6)

Honma and Tamura (1965)

Fernholm ( 1969) and Olsson

Mellinger (1969)

Tamura and Honma (1972)

Honma and Matsui (1973)

Honma and Yoshie (1974)

Bage and Fernholm (1975)

Percy et al. (1975)

Yoshie and Honma (1978)

Benjamin (1981)

Copeland (1943)

Kent (1945)

Eakin (1956)

Dongen et al. (1966)

Masur (1969)

Altland (1939)

Paris (1941)

Gabe and St. Girons (1960)

Rahn (1939)

Lampetra planeri

Xiphophorus maculatus

Salvelinus leucomaenis

Myxine glutinosa

Torpedo marmorata

Trachipterus ishikawai

Anguilla japonica

Plecoglossus altivelis

Lampetra jluviatilis

Petromyzon marinus

Rhinogobius brunneus

Pungitius pungitius

Triturus viridescens

Triturus viridescens

Hyla regilla

Bufo bufo

Notophthalmus viridescens

Sceloporus undulatus

Anolis carolinensis

Vipera aspis

Chick

FISH Meso-adenohypophysis

All regions of adenohypophysis

Proximal pars distalis

14 Examined; 1 with cyst

193 Examined; 58 with cysts

32 Examined

Adenohypophysis or ductus nasopharyngicus

Neuro-intermediate lobe

Adenohypophysis

240 Examined

207 Examined

1 Examined

Rostral pars distalis 1 Examined

Rostra1 pars distalis

Pro-, meso-, and meta- adenohypophysis

All zones of adenohypophysis


50 Examined

100 Examined; 75% with pro-adenohypophyseal cysts; 50% with meso-adenohypophyseal cysts

- Proximal pars distalis and pars intermedia

Rostra1 pars distalis

AMPHIBIA Pars intermedia and

distalis Between pars anterior

and intermedia Transplanted

pituitaries Transplanted

adenohypophysis Transplanted

pituitaries

REPTILES Pars anterior

Anterior lobe

Adenohypophysis

BIRDS Near attachment of

hypophyseal stalk


-


40 Examined

102 Examined




60 Examined; almost every gland had cyst


TABLE l-Continued


of cyst


incidence

Wingstrand (195 1)

Her-rick and McCormack (1952)

Legait (1957) and Legait and Grignon (1957)

Campbell ( 1962)

Vanderburgh (1917)

Chadwick (1937)

Opper ( 1940)

Kingsbury (1942)

Madsen ef al. (1942)

Selye ( 1943)

Wheeler (1943)

Hanstrom (1946b)

Hanstrom (1947)

Anus piatyrhynchos

Sephanoides sephanoides

Diomedea melanophis

Coragyps atratus

Phasianus colchicus

Pica pica Phalacrocorax

magellanicus Lyrurus tetrix Corvus corone

cornix Somateria

mollissima Chicken

Chicken

Fowl Pars distalis

Guinea pig

Guinea pig

Rat

Dog

cow

Rat

Didelphys aurita

Felix tigris Elephas maximus

Meles meles

Pars distalis ? Pars distalis

? Pars distalis

Pars tuberalis

Pars distalis

Pars distalis Pars distalis

Pars distalis Pars distalis

Pars distalis

Anterior lobe

Anterior lobe, pars tuberalis, pars nervosa

MAMMALS Pars intermedia,

pars nervosa, Rathke’s cleft, craniopharyngioma cyst

Anterior lobe

Pars anterior

Pharyngeal hypophysis

Between posterior and anterior lobes

Rathke’s cleft and pars anterior

Anterior lobe

Pars anterior Zona tuberalis and

pars tuberalis Pars tuberalis, pars

intermedia, glandular cysts

Total of 142 examined; 77 with cysts

67 Examined; 80% with cysts

189 Examined; 78% adults and 73% embryos have anterior lobe cysts. 5 with pars tuberalis or pars nervosa cysts

25 examined; 18 with cysts

-






100 Examined; cysts “quite common”

1 Examined 1 Examined



TABLE l--C,,tinued


of cyst


incidence

Hanstrom (1948) Hapale jacchus H. penicillata

Oboussier (1948)

Hanstrom (1950)

Shanklin (195 1)

Cercopithecus aethiops

Pa pi0 cynocephalus

P. hamadryas Troglodytes

niger Dog (many breeds

e.g., mastiff, fox- terrier, bulldog, boxer, collie, dalmation , Pomeranian dog, Scotch terrier, whippet)

Euphractus sex-cinctus

Nasua solitaria

Nycticebus coucang

Man

Hanstrom and Wingstrand (195 1)

Hanstrom (1952a)

Tachyglossus setosus

Ornithorhynchus anatinus

Aetechinus frontalis

Canis mesomelas

Zc tyonix stria tus

Myonax Cynictis

penicillata

Genetta tigrina

Felis Leo

Procavia capensis

Rathke’s cysts Pars anterior,

Rathke’s cysts, pars intermedia

Rathke’s cysts

Pars anterior

Pars anterior Rathke’s cysts,

evagination cysts Various regions of

pituitary

Pars intermedia, 2 Examined; 2 with Rathke’s cysts cysts

Pars intermedia 1 Examined

Pars intermedia

Pars anterior, pars intermedia, hypophyseal stalk, pars nervosa

Pars distalis, pars tuberalis

Pars distalis

Pars intermedia

Pars intermedia, pars distalis, Rathke’s cysts

Rathke’s cyst

Pars tuberalis Pars tuberalis,

epithelial stalk cyst

Pars intermedia, pars distalis and hypophyseal stalk

Pars intermedia, pars distalis, pars tuberalis, Rathke’s cysts

Pars intermedia


1 Examined

1 Examined


Often 1 specimen per breed

1 Examined



1 Examined

1 Examined

1 Examined



1 Examined

1 Examined



TABLE l-Continued


of cyst


incidence

Blumenthal (1955)

Ferrer (1956) Anderson and

Jewel1 (1958) Berry and

Schlezinger (1959) Hanstrom (1959)

Girod (1963)

Vijayan et al. (1969)

Ghatak et al. (1971) McGrath (197 1)

Rao and Bhat (1971) Rajan and

Mohiyudden (1973)

McGrath ( 1974)

Banna (1976)

Yoshida et al.

(1977)

Loxodonta africana

Giraffa camelopardalis

Antidorcas marsupialis

Gazella granti

Sylvicapra grimmia

Mustela putorius

Mouse

Rat Goat

Man

Manis pentadactyla

Macacus sylvanus

Funambulus pennanti

Man Man

Mongrel dog Dog

Dog, rabbit, guinea pig, cat

Man

Pars distalis Rathke’s cleft, pars

distalis, pars intermedia, pars nervosa

Pharyngeal hypophysis

Craniopharyngiomas

Man Rathke’s cleft

Pars distalis

Pars intermedia, Rathke’s cysts

Rathke’s cysts

Pars intermedia, pars distalis

Rathke’s cysts, glandular cysts

Pars intermedia

Anterior, intermediate and posterior lobes

Pars distalis Pars intermedia,

pars nervosa Rathke’s cleft cyst

Rathke’s cysts, neural lobe, pars distalis

Pars distalis

Pars distalis, pars tuberalis

Cystic craniopharyngioma Zona intermedia and

pharyngeal hypophysis

1 Examined


1 Examined

1 Examined

1 Examined


366 Examined


2 Cases




1 Examined 83 Examined; 33% with

sellar hypophysis cysts; 16% with pharyngeal hypophysis cysts

200 examined; 7% with cysts 300 Examined; 143 with

cysts

Usually 5 examined; 5 with cysts


1 Patient

Note. The original author’s terminology is used throughout.

man, 1966). Rahn, Wilson, and Legait have berty, gestation, postpartum, and after cas- even found cysts in chick embryos. Ac- tration and thyroidectomy. However, it is cording to Wilson these appear as early as unclear whether they examined enough the 10th day of incubation. Vazquez- animals to justify their remarks. Cysts are Rodriguez and Amat (1968) found that cysts more common in larger birds (Wingstrand, were common in guinea pigs during pu- 1951), but in sticklebacks there is no close


correlation between cyst incidence and body length (Benjamin, 1981). Yet cysts are more common in fish with larger pituitaries.

Classifications and Problems of Nomencla ture

The classification of pituitary cysts is difficult and confused. Previous attempts apply mainly to man and other mammals and do not easily relate to other vertebrates, other organs, or even to each other. In pathology in general, most people favour classifications that apply to many organs and are based on the pathogenesis of the lesion. It is difficult to apply this to a comparative study of pituitaries as it presup- poses that cysts are pathological. Further- more, the origin of a cyst is rarely known and is not always clear from its structure, position, or contents. Thus one can either avoid classifying cysts altogether, or use a combination of anatomical and etiological methods, according to what one knows of particular cases. With this in mind some of the existing classifications are listed in Table 2.

The reader should pay careful attention to the term “Rathke’s cleft cyst”-it can be very misleading. The term was first used by Erdheim (1904) who referred to all cysts in the zona intermedia of the human pituitary by this name. Others distinguished between a primary Rathke’s cyst (the original flat cavity of embryonic life and early child- hood) and a secondary Rathke’s cyst that results from its partial obliteration. Romeis (1940) employs the term in a most precise way. He recognises various types of cysts that are directly or indirectly related to Rathke’s cleft, but restricts the term “Rathke’s cleft cyst” to those that contain colloid and arise directly, by the fusion of the anterior and posterior walls of the original cavity. As Rathke’s cleft is normally partly obliterated in man (Romeis, 1940) and in certain other mammals (Hanstrom, 1947, 1948), one cannot always regard Rathke’s cleft cysts as “developmental

anomalies.” They are normal features of the pituitary unless they are excessively large. One should remember this when reading the medical literature, for many clinicians think otherwise. Some authors consider that all cysts in the pituitary gland develop from Rathke’s cleft. When one is dealing with a single, medical case history and a large pituitary cyst, it is impossible to be so dogmatic. In animals where the cleft does not normally obliterate, the cavity can still enlarge excessively. I think it is justifiable to call these spaces Rathke’s cleft cysts (e.g., Madsen et al., 1942).

It can be difficult to assess the literature on cystic craniopharyngiomas as the latter are also known by many other names. These include Rathke’s pouch tumour, hypophyseal duct cysts or tumours, suprasellar cysts, parasellar cysts, ada- mantinomas, ameloblastomas, Erdheim’ s tumour, craniobuccal cysts, and inter- peduncular cysts. The term “craniopharyngioma” is now generally preferred for these lesions that develop within nests of squamous cells around the pituitary gland (Banna, 1976).

The Origin of Cysts

Cysts derived directly from Rathke’s cleft. Such cysts have an anterior wall that belongs to the pars distalis and a posterior wall that belongs to the pars intermedia. In small (i.e., young) cysts, the walls can be distinguished histologically. These cysts are not limited to man and have been described several times by Hanstrom in a wide variety of mammals (see Table 1). Ac- cording to Wingstrand (1951) cysts can arise directly from Rathke’s cleft in certain birds e.g., chick embryos.

Opinions vary greatly about when the original cavity of Rathke’s pouch becomes transformed into cysts in man, and the reader is referred to Romeis (1940) for a discussion of the literature. All one can safely say is that Rathke’s cleft is more often partly obliterated in adults than in


TABLE 2 CLASSIFICATIONS OF CYSTS (ALL REFERTO MAMMALIAN PITUITARIES)

Reference Basis of classification Types of cysts

Romeis (1940)

Shanklin (1951)

Hanstrom (1952a)

Willis ( 1958)

Shuangshoti et al. (1970)

Rao and Bhat (1971)

Rajan and Mohiyuddeen (1973)

Anderson and Capen (1978)

According to their presumed origin

According to their position, structure, and origin

According to the origin of their colloid contents

According to their position (developmental cysts)

According to their position

According to their origin

According to their position

According to their origin

(1) Rathke’s cysts (2) Evagination cysts from

the zona rostralis of the pars inter-media

(3) Glandular cysts (4) Cellular cord cysts (1) Hypophyseal stalk cysts (2) Cysts of Rathke’s cleft

(a) Microfollicular (b) Macrofollicular (c) Cystic clefts (d) Multilocular

(1) Merocrine cysts (2) Holocrine cysts (1) Within parapituitary

epithelial residues (2) Within Rathke’s cleft (3) Within the pharyngeal

pituitary (4) Within intrasphenoidal

remains of Rathke’s stalk (1) Intrasellar cysts (2) Suprasellar cysts (1) Developmental cysts

(a) Rathke’s cleft cysts (b) Evagination cysts (c) Craniopharyngeal cysts

(2) Acquired cysts (a) Due to age (b) Due to nutritional

deficiency (1) Infundibular cysts (2) Cysts in pars intermedia (3) Cysts in pars distalis (4) Cysts in pars nervosa (1) Pharyngeal pituitary cysts (2) Craniopharyngeal duct cysts (3) Cystic dilation of Rathke’s

cleft (4) Atrophic cysts (5) Cysts arising from tumours

children. It is also uncertain whether Rathke’s cysts persist into old age, as it is often impossible to tell whether a cyst originated from the hypophyseal cavity early in life, or was formed later by the pars distalis in a position corresponding to that of Rathke’s cysts. This possibility, which Romeis (1940) took seriously, is rarely considered in the modem literature.

There are several ways in which Rathke’s cysts could originate from a cavity lined on both sides by epithelium (Romeis, 1940): (1) The cavity is divided by advancing cell cords from the pars distalis or by the growth of connective tissue through it. (2) The lining cells divide to obliterate the cavity. (3) The cleft discharges its colloid contents and the two walls adhere. The last


theory is the one most favoured by Romeis (1940) on the basis of his own observations. Hanstrom (1948) believes that Rathke’s cysts in Cercopithecus aethiops may arise this way. The colloid that subsequently re- forms and fills the cysts may contain degenerating cells or be homogenous (holocrine or merocrine cysts of Hanstrom, 1947). It seems that Rathke’s cysts in man and the anthropoid apes are holocrine cysts, but among the Insectivora and Car- nivora there may be either (Hanstrom, 1952a).

In Hapale jacchus, H. penicillata, Cer- copithecus aethiops, C. cynosurus and Eu- phractus sex-cinctus, Hanstrom (1948, 1950) has reported cysts that correspond to Rathke’ s cysts of man, but have originated from a well-developed pars intermedia. Rathke’s cysts in Zctyonix striatus are particularly interesting because this animal has a double layer of pars intermedia (Hanstrom, 1952a). In their position they correspond to Rathke’s cysts of man, but they are formed by the fusion of two intermedia layers.

Although the hypophyseal cleft of the shrew (Hanstrom, 1946a) and some carni- vores (Hanstrom, 1947) is partly obliterated, the two walls of Rathke’s cleft do not coalesce and no colloid is formed between them. Hence they are not what Romeis (1940) regards as true Rathke’s cysts. Nevertheless, other pars intermedia cysts are conspicuous and perhaps their development is connected with the absence of a complete hypophyseal cleft.

Cysts may be found in species where Rathke’ s cleft normally remains patent throughout life. They are well known in young dogs, especially German shepherd breeds (Anderson and Capen, 1978), and are a common cause of dwarfism. Similar cysts have also been found in several strains of mice (Blumenthal, 1955). Jubb and Kennedy (1970) refer to a congenital cystic distension of the hypophyseal lumen in chondrodystrophic calves of the short-

headed type and in congenital lymphatic hypoplasia of Ayrshire calves. Injections of hypertonic saline into male rats produced an enormously dilated Rathke’s cleft within 6 hr of treatment (Selye, 1943). Evidently the cleft was distended with colloid se- creted a few hours after the injections were given, for trypan blue administered at the same time accumulated in the cystic cleft in large quantities.

Cysts Indirectly Derived from Rathke’s Cleft

(a) Glandular cysts. It is difficult to de- cide who first recognised tubular glands in the human pars nervosa, but it was un- doubtedly Erdheim (1904) who popularised their early study. Despite many dis- agreements concerning the age at which they are found, it is certain that many give rise to cysts. Romeis (1940) refers to them as “Drusencysten” (glandular cysts). They can either form when the excretory duct is incompletely canalised or when the hypophysial cavity is obliterated. In either case a closed cavity is considerably enlarged by the continued secretion of its lining cells. One can only recognise glandular cysts with confidence when they are small, for then the lining epithelium resembles that of the normal glands. It is frequently impossible to determine the origin of large cysts, especially when the lining epithelium is flat and indistinctive. It is thus likely that many so-called “Rathke’s cysts” in man are really glandular cysts. Although they are best documented in man, they have also been reported in the badger (Hanstrom, 1947). Most standard pathology texts refer to similar cysts in many other organs, particularly the salivary glands, skin, and breast. They are generally called retention cysts.

(b) Evagination cysts. In man and certain other mammals (e.g., dog and pig), epithelial-lined tubes evaginate from the hypophyseal cavity during foetal life. Their connections with the parent cavity are gradually broken off and “ evagination


cysts” are produced (Guizzetti, 1927). They appear mainly near the hypophyseal stalk and are unstable structures liable to disappear completely or enlarge greatly. Although they originate from the posterior wall of Rathke’s cleft, their lining epithelium is distinct.

Cysts arising from cavities not derived from Rathke’s cleft. A cyst can form when watery or colloidal substances accumulate in a follicle or pseudofollicle. Such cysts are well documented in other organs, particularly the thyroid and ovary. They are usually called distension cysts. In pituitaries, such cysts include the cellular cord cysts of Romeis (1940) that characterise the zona intermedia and the pars distalis of man. Ac- cording to Romeis (1940) the cavities form because cells move away from each other and create narrow fissures.

In Lyrurus tetrix, Wingstrand (195 1) found several large cysts near the neural lobe that probably arose from colloid acini. Similarly, Opper (1940) thought the majority of cysts in the rat pars distalis were continuous with one or more sharply cir- cumscribed acini. In his opinion the acini were derived from Rathke’s cleft, but he has no evidence to support this view.

In man (e.g., Shuangshoti et al., 1970) and certain other mammals (e.g., guinea pig; Vanderburgh, 1917) cysts may arise from persistent traces of the third ventricle that formerly extended into the pars nervosa. According to Shuangshoti et al. (1970) such cysts may be indistinguishable from those arising from Rathke’s cleft.

Any distinction between distension cysts and those arising by the degeneration of cells is somewhat artificial. Even if a cyst forms from an existing cavity, it is unlikely to enlarge purely by accumulating fluid, for the latter may produce a pressure atrophy of the remaining cells and thus cause the cavity to enlarge further. The problem is that one cannot make a practical distinction between the formation and enlargement of a cyst.

My personal studies of Pungitius pitu-

itaries suggest that cysts in the rostra1 pars distalis arise by the accumulation of fluid between nongranulated cells around blood vessels, but subsequently enlarge when neighbouring cells also degenerate (Benjamin, 1981). Ghatak et al. (1971) have also suggested that certain craniopharyngioma cysts arise by the massive expansion of extracellular spaces. In Pungitius, cysts are more common in animals with large pituitaries, and the rostra1 pars distalis of such animals has a proportionally richer blood supply than in smaller glands. Hence it was proposed that cysts develop in Pun- gitius either when vascular demands or vascular supplies become too great.

Cysts arising by the degeneration of cells. Many authors have suggested that cysts arise by the degeneration of adenohypophy seal cells, particularly basophils. This is the most likely origin of the pars distalis cysts described by Selye (1943) in the rat. Rahn (1939) thinks that large mu- cous cells in embryonic avian pituitaries give rise to ciliated cells, and Wingstrand (1951) has suspected the same. Many of the cavities arising by the disintegration of gonadotrophs that accompanies sexual maturation in trout (Robertson and Wexler, 1962) could be regarded as cysts. They occur at the same time as others that arise as enlarged follicles within the prolactin cell zone. In Myxine glutinosa, Fernholm and Olsson (1969) refer to basophil cysts that may originate from enormous, degenerating, PAS-positive cells. It is tempting to suggest that some cysts that form from degenerating basophils are a dramatic expres- sion of cellular exhaustion.

Most cysts in Pungitius pituitaries mainly enlarge by the death of acidophils (prolactin cells) and nongranulated cells, but a minor- ity do so by the disintegration of basophils (see Benjamin, 198 1, for references). In Lampetra planeri, Kamer and Schreurs (1959) refer to one cyst that develops at the expense of chromophobic cells that are the probable source of growth hormone.

Various tumours can degenerate to pro-


duce cysts. This is best documented for human craniopharyngiomas (see below), but adenomas can also be cystic (Dott and Bailey, 1925). Degenerative cysts in general are usually ischaemic in origin. This may reflect a general vascular disease or locally inadequate blood supplies. Cysts are particularly common in the mammalian pars intermedia-a region of the pituitary that often has a sparse blood supply (e.g., Van- derburgh, 1917). Oordt (1968) has proposed that some pituitary cysts in higher vertebrates arise from a disrupted portal circulation. Certainly, necrosis of the rat pars distalis can be induced experimentally by cauterizing the vessels around the pituitary stalk (Daniel and Prichard, 1956). Possibly such necrotic areas could be transformed into cysts if the experiments had been of a longer term. Daniel and Prichard point out that in any general failure of the peripheral circulation, the mammalian pituitary is particularly susceptible to necrosis, for it re- ceives’portal venous blood that has already passed through a capillary bed.

Horvath et al. (1974) have suggested that follicles develop in the human pars distalis around foci of ruptured and disintegrating endocrine cells. They suggest that the lining cells of a follicle are derived by the de- granulation and dedifferentiation of adenohypophyseal cells and that they seal off the intercellular spaces to prevent proteolytic enzymes from destroying hormones elsewhere. This is certainly an attractive way of explaining the significance of at least some cysts in the pars intermedia, for the degeneration of its basophils is well documented in the early literature (Romeis, 1940).

Cysts derived from the craniopharyngeal duct. Cysts may form around the pituitary stalk and pars tuberalis in man and are widely considered to be of developmental significance and to have originated from clusters of cells derived from the distal end of the craniopharyngeal duct. Erdheim (1904) first popularised the idea and his theory is seldom questioned today, though

Hunter (1955) considers that many of the cell nests arise by the metaplasia of differ- entiated pituitary cells. The cell groups give rise to tumours (craniopharyngiomas) and it is within these that the cysts develop. The tumours are particularly common in children (Banna, 1976).

Similar cysts developing from the distal part of the craniopharyngeal duct are well documented in brachycephalic breeds of dogs (Anderson and Capen, 1978), but have also been recorded in many other animals e.g., the guinea pig (Vanderburgh, 1917), chicken (Legait, 1957; Campbell, 1962), and the palm squirrel (Vijayan et al., 1969).

In some mammals the proximal portion of the craniopharyngeal duct persists in the adult and forms a pharyngeal hypophysis embedded in the mucoperiosteum of the pharynx (McGrath, 1974). In the dog this structure is normally cystic and the cysts arise by the persistence of the craniopharyngeal duct lumen (Kingsbury, 1942; McGrath, 1974). The duct opens onto the pharyngeal surface. As with developmental cysts in the sellar hypophysis of dogs, a cystic pharyngeal hypophysis is most characteristic of brachycephalic breeds (Ander- son and Capen, 1978). Presumably cyst development in dogs is influenced by growth mechanics in other parts of the head. In the guinea pig, the pharyngeal hypophysis is not only cystic and opens into the pharynx, but is also continuous with the sellar hypophysis (McGrath, 1974). Perhaps cyst development in one hypophysis (human sellar or pharyngeal) influences cyst development in the other. McGrath (1971) found four cases where there were cysts in both.

Parasitic cysts. On rare occasions, cystic stages in the life history of parasites are reported in pituitary glands. Hanstrom (1952a) refers to cysts of a coccidian-like parasite in the pituitary of a Grant’s gazelle and Copeland (1943) found a parasitic cyst (unnamed) in the pituitary of Triturus viridescens. According to Prosser el al. (1978) there were encysted larvae of Taenia sol-


ium within the pituitary capsule of a patient on whom they operated.

Cysts as “normal” structures. Cysts are not always pathological features, but are often regarded as such. Parts of some pituitaries are normally hollow e.g., in certain teleosts, chondrosteans, and elasmo- branchs (Mellinger, 1969; Cook et al., 1973; Holmes and Ball, 1974; Olsson and Fujita, 1976), but few authors call such cavities cysts. It would seem justifiable to do so, as they can be structurally identical and may even form in similar ways.

In a wide variety of animals many authors have found cysts in more than 50% of the population (see Table 1). Although one could regard such cysts as normal features in the sense that they are relatively constant and probably harmless, perhaps they are pathological in so far as we can recognise a lesion and trace its evolution or cause. Clearly this is a question of definitions. Both Romeis (1940) and Wingstrand (1951) regard cysts in certain pituitaries as normal features.

The Growth of Cysts

Though cysts can arise in different ways, they may enlarge by some common mecha- nism. Pituitary morphologists have not considered these possibilities in detail, but several theories have been proposed to account for the enlargement of epithelial jaw cysts in man (Main, 1970) and the principles are so fundamental that they could also apply to pituitaries.

panying the disintegration of cells into the cavity. In both cases the osmotically active substances are protein, and gel-electropho- retie studies of colloid in Rathke’s cysts of the rat have clearly shown additional proteins that are absent from normal glands (Rapp and Dahl, 1974). One can largely dismiss the possibility that the fluid contents of cysts are exudates from acute inflammation, as polymorphonuclear leu- cocytes are rarely found around cysts. Although lymphoid tissue can occur in pituitary glands (Romeis, 1940; Wingstrand, 1951) it is unlikely that defective lymphatic drainage could explain the growth of pituitary cysts, but it is possible that venous drainage is insufficient and that fluid ac- cumulates as a transudative oedema (Main, 1970).

Perhaps cysts enlarge merely by the proliferation or degeneration of pituitary cells. This is an attractive way of explaining multilocular cysts, for presumably these cannot enlarge by accumulating fluid. Of course they could form by the fusion of several small cysts. If cell proliferation is important, one should find mitosing cells in the cyst wall. This does not often happen.

An important factor in the expansion of pituitary and jaw cysts may be an internal hydrostatic pressure inducing the atrophy or resorption of surrounding tissues. Cer- tainly pituitary cysts in man can bulge be- yond the gland outline and press on neighbouring structures. It is often such effects that produce the clinical symptoms (see below). The increased pressure could arise by the secretion of neighbouring cells

It is difficult to estimate the rate at which cysts enlarge. It varies greatly and depends on the experimental treatment and the pathogenesis of the cyst. Large ones can appear in rat pituitaries within 6 hr of hypertonic saline injections (Selye, 1943) and are certainly present 30 days after castration (Ferrer, 1956). They can be induced in Pungitius within 3-4 weeks of starving the fish or transferring them to seawater (see Benjamin, 1981, for references). On the basis of somewhat tenuous evidence, Madsen et al. (1942) have suggested that cows may not be able to repair cysts induced by vitamin A deficiency. An interesting study is that of Raskind et al. (1968) who reported a human pituitary cyst that recurred 26 years after an operation to

or by the increased osmolarity accom- incise it.


The Structure, Position, and Contents of cysts

Cysts may be single or multiple, uni- locular or multilocular. They can have stainable contents or else appear “empty” when examined microscopically. They vary enormously in size, from tiny follicles to huge bladders that are readily visible to the naked eye. Stockard (1941) has reported an extreme case where a pituitary cyst in a dog was so large that it totally destroyed the rest of the gland.

Modern pathologists often demand that cysts should have an epithelial lining, though it is difficult to see why. It clearly creates problems, because many lesions that have long been called cysts must now be termed “pseudocysts.” I suspect the demand for an epithelial lining quietly ap- peared and spread without any logical basis. Cysts have been found in every part of the gland though are most typical of the pars intermedia. Most of our information is based on light microscopy studies. Only a few authors have studied the ultrastructure of cysts (e.g., Ghatak et al., 1971; Yoshida et al., 1977; Benjamin, 1981).

When cysts have an epithelial lining, this may be single layered (e.g., Vanderburgh, 1917; Opper, 1940; Girod, 1963; Rajan and Mohiyudden, 1973; McGrath, 1974), pseudostratified (Berry and Schlezinger, 1959; Rao and Bhat, 1971), or at least partly multilayered (e.g., Kingsbury, 1942; Shanklin, 1949; Herrick and McCormack, 1952; Shuangshoti et al., 1970). The outer cells of a stratified epithelium are usually flattened, though occasionally cuboidal or columnar (Shanklin, 195 1). A single-layered epithelium may have squamous, cuboidal, or columnar cells. Whenever authors have looked carefully at a sufficient number of cysts, they have usually found considerable variations in any lining epithelium. Many authors have commented that larger cysts are lined by flatter cells (Romeis, 1940;

Hanstrom, 1946b; Wingstrand, 1951; Campbell, 1962). It is usually assumed that the cells flatten as the cyst enlarges because of the pressure of the luminal contents. Perhaps this is why large cysts in guinea-pig pituitaries were burst (Vazquez-Rodriguez and Amat, 1968). Cysts frequently have a connective tissue capsule (e.g., Shanklin, 1949, 1951; Berry and Schlezinger, 1959; Vijayan et al., 1969) and this could be a device for resisting pressure. Yet such cysts do not always have a flattened lining!

A number of authors have noticed similarities between the epithelia lining cysts and those elsewhere, particularly in the re- spiratory tract, buccal cavity, and nasopha- ryngeal canal (Wheeler, 1943; Hanstrom, 1947; Shanklin, 1951; Schreibman, 1966; Rao and Bhat, 1971). Such observations have been used to support the contention that some pituitary cysts arise from tissue that is misplaced during development.

Some cysts lack an epithelial lining. Maybe one is present, but is flattened and difficult to see, or perhaps it is lost during the preparation procedures. In Pungitius cysts that have any lining at all, there is a prominent basal lamina at the border between the cavity and the cyst wall (see Benjamin, 1981, for references). Deep to this is a layer of nongranulated cells that prevent the prolactin cells from touching the cyst cavity. It is worth noting that Ghatak et al. (1971) described lining (stellate) cells with a distinctive surface coat in cystic craniopharyngiomas of man. Compa- rable findings are also reported for various cavities in the pituitaries of Scyllium canicula (Alluchon-Gerard, 1971), En- graulis japonica (Olsson and Fujita, 1976) and certain chondrostean and holostean fish (Lagios, 1973). Perhaps the nongranulated cells with their prominent surface coat or basal lamina control the exchange of substances between the cyst cavity and the intercellular spaces. According to Cook et al. (1973), prolactin cells can discharge


their contents into the hollow rostra1 pars distalis of Alosa pseudoharengus. At the sites of release, the nongranulated cells separate, allowing the endocrine cells to contact the lumen directly.

There are numerous reports of mucus- secreting cells and cilia in the lining epithelium (e.g., Rahn, 1939; Shanklin, 1951; Legait, 1957; Legait and Grignon, 1957; Girod, 1963; Rao and Bhat, 1971; Rajan and Mohiyuddeen, 1973). They do not always occur together (Shanklin, 1951; Schreib- man, 1966). In general, cilia bordering colloid cavities in pituitaries have a 9 + 2 ar- rangement of microtubules that suggests they are motile.

Cyst linings can also contain normal adenohypophyseal cells and various degenerating cells (Vanderburgh, 1917; Kent, 1945; Hanstrom, 1952a; McGrath, 1971). The latter contribute by their holocrine secretion to the cyst contents. It is remarkable that seemingly healthy adenohypophyseal cells can be discharged into cyst cavities, sometimes in considerable numbers. A few of these cells degenerate immediately, others transform into enormous cellular spheres (Romeis, 1940; Hanstrom, 1948; Wingstrand, 195 1).

There are phagocytic cells in both the walls and cavities of cysts (Romeis, 1940; Benjamin, 1981). In Pungitius, they lie mainly at the edge of the cavity, though perhaps others were lost in processing (Benjamin, 1981). They can engulf large portions of prolactin cells. It is tentatively proposed that the phagocytic cells are derived from nongranulated cells in the rostra1 pars distalis.

The colloid content of pituitary cysts is considered in detail later. However, there are other contents that should be briefly mentioned here. Ghatak et al. (1971) found keratin and presumptive calcium salts within the cyst lumen of a craniopharyngioma in man. This would certainly confirm the abundant light microscopy and radio- logical evidence that cystic craniopharyn-

giomas are calcified and lined by an epithelium whose superficial cells are often keratinised. Cholesterol deposits are common in cysts (e.g., Rajan and Mohiyud- deen, 1973), although Shanklin (1951) has failed to find them in man.

The Genetic Basis of Pituitary Cysts

The dog has more diverse and numerous breeds than any other mammal. Both the gross anatomy and the finer histological details of its pituitary vary greatly. In certain breeds the pituitary is fairly normal (e.g., dachshund), whereas in others (e.g., Boston terrier) there are usually one or more cysts in the pars distalis. In crosses between dachshunds and Boston terriers, the pituitaries of all Fl hybrids were cystic (Stockard, 1941). That the Boston terrier pituitary pattern was dominant over the dachshund type was confirmed by analys- ing the F2 hybrids. It was also clear that specific differences in physical characters among the F2 hybrids were closely linked with histopathological changes in the pituitaries.

Pituitary cysts in Xiphophorus are only common in one strain (Schreibman, 1966). Schreibman believes that the cysts have a polygenic basis and may arise from in- breeding. According to Rapp et al. (1979), pituitary cysts in rats (dilated Rathke’s cleft) have a polygenic inheritance that is mainly influenced by a single gene.

Effects on Other Structures

In man, the majority of cysts loosely described as Rathke’s cleft cysts are asymp- tomatic. It is only when they are especially large that they produce clinically recognis- able symptoms (Berry and Schlezinger, 1959; Yoshida et al., 1977). According to Berry and Schlezinger (1959), reported cases fall broadly into two groups-(l) patients with suprasellar symptoms that often give the preoperative impression of chromophobe adenoma. The patient’s eyesight is poor and they may suffer from


headaches. (2) Patients showing clinical symptoms of hypophyseal dysfunction e.g., hypophyseal cachexia and diabetes insipidus. Similar symptomatic cysts have been reported in dogs, where they commonly cause dwarfism (Anderson and Capen, 1978). The puppy haircoat is re- tained and the animal does not mature. Diabetes insipidus is common and there are changes in the thyroid and adrenal glands. Cystic craniopharyngiomas in man produce a variety of clinical symptoms that partly depend on the direction of tumour growth and its relation to the hypothalamus (Banna, 1976). They generally include endocrine and visual disturbances. The same symptoms may also occur in domestic animals (Anderson and Capen, 1978).

Researchers studying pituitary cysts in lower vertebrates are not concerned with clinical symptoms, but have still reported accompanying changes in other organs. According to Robertson and Wexler (1962) large cavities appear in trout pituitaries as sexual maturation approaches. The inten- sity of change parallels the physical deterio- ration of the fish. The formation of cysts in the future gonadotrophic zone of Xipho- phorus may affect gonadal development, as all fish with poorly developed gonads also had well-formed cysts (Schreibman, 1966). In Pungitius, cysts are particularly interesting as they are nearly always re- stricted to the prolactin cell zone of the rostra1 pars distalis and may severely di- minish cell numbers (see Benjamin, 1981, for references). In animals with large cysts, so few prolactin cells remain that the animal is partly hypophysectomised. In such animals there are changes in the thickness of the epidermis and the number of its mu- cous cells, similar to those one might ex- pect from decreased circulating levels of prolactin (Benjamin, 1980).

COLLOID Types of Colloid

Large masses of colloid may be con-

spicuous in Rathke’s cleft, cysts, follicles, tubules, or acini. They are also characteristic of the cavities in elasmobranch pituitaries (Mellinger, 1969). Smaller droplets occur within and between cells and within the lumina of blood vessels. It is most unlikely that all these colloids have the same origin or significance. Hanstrom (1947, 1948, 1952a) consistently distinguishes between holocrine and merocrine colloid according to the presence or absence within it of degenerating cells. Many authors recognise different types of colloid according to their staining reactions and in particular distinguish azan red from azan blue colloid (Romeis, 1940). The staining affinity of a colloid may not be uniform. This could reflect chemical differences or regional variations in concentration. Romeis (1940) thinks that younger colloid is more fluid and stains blue with azan. More recently, there have been several histochemical studies on various colloids and most are at least partly PAS positive (e.g., Pearse, 1952). Accord- ing to Gabe and Saint Girons (1960) the colloid of cysts in viper pituitaries is stratified and its eosinophilic zones are rich in amino acids and sulphydryl proteins, while the cyanophilic zones contain large amounts of neutral mucopolysaccharides and glycoproteins. Many have suggested that colloid contains mucins and both Guiz- zetti (1927) and Pearse (1952) have shown some colloids to be metachromatic. Ac- cording to Romeis (1940) the way in which colloid originates influences its staining reactions, for when it is formed by holocrine secretion, even newly formed colloid is azan red.

Special forms of colloid have been found in man, the large-spotted genet, and the Af- rican elephant (Rasmussen, 1933; Wislocki, 1940; Hanstrom, 1946a, 1952a; Shanklin, 1948a,b). Here there are calcified structures resembling the concretions that are better documented in the pineal and prostate. They are hard structures that often nick the microtome knife and consist of several con-


centric layers of intensely staining material. According to Shanklin (1948a) there are two types of concretions in human pituitaries-those developing around enlarged mesothelial cells in the capsule and those developing within pars distalis follicles. Filmy membranes of colloid between pituitary cells may also be calcified (Hanstrom, 1952a). They are transparent and lightly staining and reminded Hanstrom of glass. Wislocki (1940) has demonstrated iron deposits in the colloid and lining cells of follicles in the elephant pars distalis.

Colloid can occur in blood vessels (Ras- mussen, 1927; Romeis, 1940; Hanstrom, 1948, 1952a,b). We do not know how it gets there and it evidently does not happen very often. Romeis (1940) is careful to point out that many reports of intravascular colloid really refer to coagulated blood plasma. This does not apply to the literature cited here.

Not all colloid within the pars nervosa represents stored neurosecretion. It is characteristic of man and certain other mammals that pars intermedia cells and perhaps whole follicles can invade the neural lobe (Romeis, 1940; Hanstrom, 1952a; Anderson and Jewell, 1958). Such cells may disintegrate and produce colloid. This is thought unlikely by Hanstrom (1952a) who does however propose that the colloid content of invading follicles is dis- persed among the nerve fibres and pitui- cytes of the pars nervosa.

A few authors have described the ultrastructure of pituitary colloid. The study by Abel et al. (1971) of the herring gull pituitary is particularly interesting as this is one species that Wingstrand (1951) regards as having a large amount of colloid. It con- sists of a homogeneous ground substance in which there are numerous ribosomes and 7 nm, banded crystalline structures. Small channels of colloid could be enclosed en- tirely within a single stellate cell.

The Formation of Colloid

There is a great deal of controversy about

how pituitary colloid forms, particularly that in Rathke’s cleft. Romeis (1940) has comprehensively reviewed the early literature. Many assume colloid forms from degenerating cells in the pars distalis and only later collects in Rathke’s cleft or its cysts. Selye (1943) is convinced that cleft colloid in the rat partly forms this way. Others think that the lining cells of the cleft disintegrate to produce the colloid. Indeed this is the personal view of Romeis (1940). He also thinks an essential part of the cleft colloid in humans is formed by the evaginations and tubular glands that are characteristic of man. Even within one species there are widely differing views on how colloid forms. Ferrer (1956) believes the posterior epithelium of Rathke’s cleft in the rat forms colloid by apocrine secretion, whereas Vanha-Perttula and Arstila (1970) think that the lining cells absorb colloid rather than produce it. It is also possible that the cleft contents partly arise by the transudation of plasma from capillaries near the cleft. Cer- tainly Selye (1943) has demonstrated a rapid concentration of intravenously in- jected trypan blue within Rathke’s cleft. Rapp and Dahl (1974) recognise two ways in which colloid proteins may form-from the intermediate lobe cells via the intercellular spaces or directly from the lining cells. Boyd (1972) has suggested that cleft colloid in cow pituitaries is formed by the cyclic degeneration of marginal cells lining the intermediate lobe. These cells autolyze, break away from the underlying pars intermedia, and enter the cleft lumen. Here they further degenerate and form the colloid. Exceptionally large numbers of degenerating cells have been found in the cleft lumen of man (Romeis, 1940), the guenon and the chimpanzee (Hanstrom, 1948) and the South-African hedgehog (Hanstrom, 1952a). According to Hanstrom (1948) they have migrated into Rathke’s cleft, where they absorb fluid, attain a considerable size, and then degenerate completely, thereby con- tributing to colloid formation.

Larger masses of colloid often have mar-


ginal vacuoles similar to those in the thyroid. They may be shrinkage artefacts or signs of colloid formation or absorption (Romeis, 1940; Vanha-Perttula and Arstila, 1970). If they are associated with colloid formation they could represent the apical droplets of marginal cells that have yet to mature into colloid.

There is no agreement at all about how small droplets of colloid form. Many have suggested that acidophils, basophils, and chromophobes, together or individually, may degenerate and form colloid. Others see it as a secretory product that starts as intracellular droplets (Romeis, 1940; Han- Strom, 1952a). Colloidal spheres within and between pars intermedia cells of the perch (Kerr, 1942) are probably secretion droplets, as similar masses in the minnow lie within the endoplasmic reticulum (Benja- min, 1975). Intracellular droplets in pars intermedia cells of the toad, Bufo are- narum, may contain stores of MSH (Itur- riza and Koch, 1964). In the lizard, Calotes versicolor, Nayar and Pandalai (1963) claim that colloid droplets accumulate in pars intermedia cells when MSH is actively produced. According to Wheeler (1943) certain basophils in the opossum transform completely into “colloid cells” in loo-day-old animals. Some of these cells may reach >50 pm in diameter. He did not know the significance of this colloid, but commented that the cells were absent from younger or older animals and that they imparted to the whole gland an appearance of long-term castration. Another curious finding is the colloid droplets within the nuclei of certain adenohyophyseal cells in the ferret (Hanstrom, 1952a). Presumably they deep- ly invaginate the nucleus rather than lie within it.

The Significance of Colloid

Although the significance of most colloids is unknown, some authors have firm ideas on its importance in Rathke’s cleft. For a considerable time Boyd and his colleagues (see Boyd and Peters, 1980, for ref-

erences) have been studying the cleft colloid of cow pituitaries. They regard it as a holocrine secretion of the lining cells that is stored in the lumen and releases im- munoreactive substances into the cerebrospinal fluid or cavernous sinuses. Changing activity of the intermediate lobe may control the protein (? hormonal) content of the cerebrospinal fluid. Rapp and his colleagues (see Rapp and Bergon, 1977, for references) think cleft colloid influences blood pressure and sodium metabolism in rats. They found large amounts of it in animals resistant to the hypertensive effects of a high-salt diet. The colloid contained various proteins not usually found in serum. Many other authors have commented on a relation between salt or water intake and colloid accumulation in Rathke’s cleft (e.g. Selye, 1943; Ciocca and Gon- zalez, 1978).

In a variety of mammals, other procedures affect the amount of cleft colloid, e.g., adrenalectomy and castration (Ferrer, 1956; Dingemans and Feltkamp, 1972), pituitary transplantation (Masur, 1969; Dinge- mans and Feltkamp, 1972)) and radiothy- roidectomy (Dingemans and Feltkamp, 1972). Lewis et al. (1937) claim to have found MSH in the water exudate accompanying the colloid in steer and cow pituitaries and Anderson and Jewel1 (1958) have reported high MSH and antidiuretic activities from colloid extracts of cysts in goat pituitaries. Many believe that colloid elsewhere in the pituitary may accumulate with age (Chadwick, 1937; Wolfe, 1943; Wingstrand, 1951) or is more conspicuous in stressed animals (see Abel et al., 1971, for references). In the elasmobranch, Tor- pedo marmorata, Mellinger (1969) has proposed that the ventral lobe cavity and its colloid and “giant lining cells” contribute to the gonadotrophic and thyrotrophic functions of the pituitary.

It is not enough to dismiss colloid as a waste product of cell degeneration. Some colloids may be no more than that, but others play a more positive role and should


interpretation of present-day findings and

not be neglected in contemporary research. We need immunocytochemical data on

for directing future research that could be

many colloids and a further study of those animals where colloid vesicles are so

attained from a knowledge of their work.

numerous that sections of the pituitary re- semble those of the thyroid. Wingstrand (1951), Hanstrom (1952a), and Holmes and Ball (1974) mention several such glands

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cysts (large follicles) and colloid in pituitary glands

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