Physiological Mechanisms

Hormonal Control

Dr Smita Bhatia BP-5, II floor,

Shalimar Bagh (West) Delhi 110088

Contact: 27483738 Email: smitabhatia@edscientia.com

1

Learning objectives

Chemical nature of hormonesTransport of hormonesMechanism of hormone action Hormone interactionsControl of hormone secretionClearance of hormonesMajor endocrine glands, their secretions and disorders

Hypothalamic-hypophyseal axisThyroid glandParathyroid glandsAdrenal glandsPancreatic isletsGonads and placenta ThymusPineal gland

Other endocrine tissues

In addition to other homeostatic mechanisms of the body, one of the two major regulatory systems of the body is the endocrine system (the other being the nervous system). This system comprises the endocrine glands that release their secretions, called hormones, into the blood stream which transports it to the various target organs on which these hormones act to activate, inhibit or, modify certain functions. Hormones are released into the blood stream rather than directly reaching the target organs because these glands have no ducts (ductless glands) to convey their secretions (also because there could be many target organs for a single hormone so it would not be possible to take these secretions to each and every organ by means of ducts).

Why do hormones act on certain specific organs and not on others?

This is due to the presence of receptors in/on the target cell. These receptors are protein, or glycoprotein molecules, which can bind to the hormone. The location of receptors differs within a cell for different types of hormones. These receptors may be present:

• On the cell: For the protein peptide and catecholamine hormones.

• In the cytoplasm of the cell: Steroid hormones (since these hormones can readily enter a cell).

• In the cell nucleus: Thyroid hormones (as these hormones can readily enter the cell because of their lipid soluble nature) where they directly affect the genes.

A specific change occurs after the hormone binds to the receptor (see mechanism of hormone action). The number of receptors on the cell surface is regulated by the concentration of the circulating hormone. If the concentration is very high the number of receptors decreases so

2

that the cell becomes less sensitive to the hormone. This is known as down-regulation. If the concentration of the hormone becomes low, the number of receptors increases to increase the sensitivity of the cell to the hormone. This is known as up-regulation.

C

H

PP

Differences between the two major regulatory systems of the body—the endocrine and the nervous system

Nervous system Endocrine system • Neurotransmitters are released which • Hormones are released which can be

act locally • Act on muscle cells, gland cells and

other neurons • Effect of neurotransmitters occurs

within a short span of time (msec) • Effect lasts for a short time (msec)

carried anywhere in the body • Act on a variety of cells • Effect of hormones may take seconds

to hours to days to occur • Effect may last for a long time (seconds

to days)

Functions of hormones

• Help to regulate the chemical composition and volume of the various components of the body, e.g. plasma, interstitial fluid.

• Help regulate the metabolism and energy balance.

• Help regulate the contraction of smooth and cardiac muscle fibres.

• Help regulate glandular secretion and some immune system activities.

• Control growth and development.

• Regulate the functioning of the reproductive system.

• Help establish circadian rhythms.

• Help regulate the interaction between the environment and the body.

hemical nature of hormones

ormones are of different types:

rotein or peptide hormones. These are made up of amino acids. They are water soluble. eptides are made up of 3 to 49 amino acids. e g. oxytocin and insulin. Protein hormones are

made up of 50 to 200 amino acids e.g., thyroid stimulating hormone (TSH), follicle stimulating hormone (FSH). These are produced as biologically inactive precursor molecules (pre-prohormones) by the rough endoplasmic reticulum of the gland cell. These pre-prohormones are then cleaved into prohormones which are also biologically inactive. Prohormones are then packaged into vesicles as hormones by the Golgi body. These vesicles

3

are stored in the cytoplasm near the plasma membrane from where they are secreted by exocytosis on an appropriate stimulus.

Steroid hormones. These hormones are derived from cholesterol e.g., testosterone, cortisol, progesterone. They are lipid soluble. These are not stored in the cytoplasm but are synthesized from cholesterol when needed and are secreted directly by passing through the plasma membrane as they are lipid soluble.

Biogenic amines. They are derived from amino acids. They are of different types:

• Thyroid hormones and catecholamines. Thyroxine (T4) and triiodothyronine (T3) are secreted by the thyroid gland. Catecholamines include epinephrine and non-epinephrine secreted by the adrenal medulla and dopamine secreted by the hypothalamus and other brain cells. They are all derivatives of the amino acid tyrosine. Thyroxine is synthesized in the thyroid follicles where they are stored with thyroglobulin (a glycoprotein). When needed, thyroxin is released from the thyroglobulin into the blood where it combines with the thyroxin-binding globulin. Catecholamines are stored in the vesicles in the cytoplasm which are released by exocytosis when needed. Catecholamines are water soluble while thyroid hormones are lipid soluble because they are iodinated.

• Histamine secreted by the mast cells is derived from amino acid histidine.

• Serotonin (or 5-hydroxytrptamine, 5-HT) and melatonin. Both are derived from the amino acid tryptophan. Serotonin is secreted by certain brain cells and melatonin is secreted by the pineal gland.

• Eicosanoids. These are different types of hormones derived from the fatty acid arachidonic acid containing 20 carbon atoms. Eicosanoids include prostaglandins (like PGF2α), prostacyclins and leukotrienes. These are water-soluble.

• Nitric oxide. Though it is a gas, it is produced as a hormone as well as a neurotransmitter. It is lipid soluble.

Transport of hormones The secretion, transport and mechanism of action of these hormones depends on their polar or non-polar nature i.e., whether they are water soluble or lipid soluble.

The water-soluble hormones do not need any carrier molecules in the plasma, where they can circulate freely in the aqueous medium. But lipid-soluble hormones cannot be transported as free molecules in the aqueous plasma and are transported by carrier proteins. In addition to transporting these hormones these carrier proteins also,

• Prevent filtration of small lipid hormones through the glomerulus in the kidneys thus increasing their half-life.

• Provide a readily available stock of these hormones circulating in the blood.

4

Mechanism of hormone action

Lipid soluble hormones

Lipid-soluble hormones bind to the receptors present inside the target cells because these hormones can cross the plasma membrane.

Sequence of events of the action of a lipid molecule Lipid hormone is released from the blood into the interstitial space

It crosses the plasma membrane of the cell and binds to specific receptors inside the cell

The hormone-receptor complex turns certain specific genes on or off.

Synthesis of certain specific mRNA (and hence specific

5

Water soluble hormones Since these hormone molecules cannot enter the cell they bind to receptors on the surface of the target cell and trigger the formation of another molecule within the cell. Here, the hormone molecule is known as the first messenger molecule and the molecule formed within the cell due to its binding is known as the second messenger.

Sequence of events of the action of a water molecule (Figure 1) Water-soluble molecule binds to the receptor (it is a transmembrane protein) on the surface of the molecule

Hormone-receptor complex activates a membrane bound (bound to the inner side of the plasma membrane) protein—the G-protein (which binds to a GTP molecule and releases a GDP molecule)

G- protein activates enzyme adenylate cyclase

Adenylate cyclase catalyses the conversion of ATP into cyclic AMP (cAMP). (This cAMP is the second messenger)

cAMP activates a protein kinase

Protein kinase phosphorylates other cellular proteins

On phosphorylation some cellular proteins get activated while some other get inhibited

Some physiological processes are stimulated or inhibited (depending upon whether the protein regulating this process has been activated or inhibited)

After some time an enzyme phosphodiesterase breaks down the second messenger to stop this sequence of events till another hormone molecule binds to the receptors to trigger this again.

Fig 1: Mechanism of G-protein mediated action of water soluble hormones

6

Different protein kinases exist in different cells or within the same cell, while one type of

protein kinase may stimulate an activity by phosphorylating a protein another protein kinase may inhibit another activity by phosphorylating another protein.

In addition to cAMP, other second messengers include cGMP (cyclic guanosyl monophosphate), inositol phosphate (IP3) and diacyl glycerol (DAG). Nitric oxide which causes vasodilation by stimulating the relaxation of smooth muscle fibres in blood vessels acts by stimulating the formation of cGMP (the secondary messenger) which stimulates the transport of Ca2+ into storage areas of the smooth muscle fibre from the cytosol. When cytosol Ca2+ ion concentration decreases it results in the relaxation of muscle fibres.

Some hormones cause the opening or closing of specific ion-channels in the cell membrane to initiate the entry or exit of certain ions to produce a specific effect (this effect may be produced through the G-protein).

Hormone interactions

The action of a hormone is dependent upon

• Its concentration in the plasma • The number of receptors of the hormone • Interaction with other hormones

In addition to the concentration of the hormone and the number of receptors present a hormone’s interaction with other hormones also affects its effectiveness. The different types of interactions that a hormone can have with other hormones are:

• Permissive effect. When prior exposure to one hormone facilitates the action of another hormone, e.g. exposure of the uterine cells to estrogen and FSH during follicular phase facilitates the action of progesterone during the luteal phase of the menstrual cycle. Exposure to estrogen and FSH also causes the development of receptors for progesterone in the uterine cells.

• Synergistic effect. When the effect of two hormones is greater than their independent effects. Thus, these hormones work together to produce an effect, e.g. both FSH and estrogens are required for the development of an ovarian follicle.

• Antagonistic effect. When the effect of one hormone is opposite to the effect of another hormone, e.g. parathyroid hormone from parathyroid gland increases blood calcium levels while calcitonin from C cells of thyroid reduces blood calcium levels. Normally, antagonistic hormones are not released at the same time because that would be a waste of energy.

Control of hormone secretion

Secretion of a particular hormone can be regulated by three mechanisms:

• By neural control, e.g., release of epinephrine and nor-epinephrine from the adrenal medulla is controlled by the sympathetic nervous system.

7

• By another hormone, e.g. release of thyroxin from the thyroid gland is stimulated by the thyroid stimulating hormone (TSH) from the anterior pituitary.

• Through negative or positive feedback:

Negative feedback

When the secretion of a hormone is inhibited by an effect produced in the target cell, e.g. FSH that stimulates the secretion of estrogen from the ovary is suppressed when estrogen levels reach a particular concentration. The effect produced (secretion of estrogens) by a hormone (FSH from the anterior pituitary) inhibits the secretion of the hormone (FSH) that caused it (Figure 2).

Fig 2: Negative feedback control

FSH from anterior pituitary

Follicles in the ovary are stimulated

Estrogen secretion

Increased levels of estrogen Shows the negative feedback

–

Positive feedback

Secretion of certain hormones is stimulated by the effect that it produces, e.g. oxytocin from the posterior pituitary enhances uterine contractions during parturition (birth of a baby). This causes the baby to descend to the cervix, further stretching the cervix which further stimulates the release of oxytocin. The positive feedback cycle is broken by a sudden change in the events of the cycle, e.g. in case of oxytocin, the cycle breaks when the baby is born.

In addition to the positive and negative feedback regulation of the hormone secretion there are periodic variations in their secretion also. These variations are dependent on seasonal changes, the circadian rhythm (an inherent rhythm), aging, stages of development and sleep, e.g., the levels of growth hormone increase during early stages of sleep and then reduce.

Clearance of hormones

• Binding with tissue. Once a hormone binds to a receptor, it is internalized and the hormone is degraded and the receptors are recycled.

• Metabolic destruction by the tissue, e.g. the water soluble hormones (proteins and catecholamines) are degraded by enzymes in the blood and tissues and excreted by the kidneys.

• Excretion by liver into bile, e.g. the steroid hormones which are conjugated in the liver and secreted ("excereted") into the bile.

• Excreted by the kidneys.

8

Hormones that are bound to plasma proteins have a longer half life.

Half-life of a hormone. The time taken for the levels of a hormone to be reduced to half

of its original concentration is known as its "half-life". Hormones like angiotensin II have

a half-life of less than a minute while others such as the thyroid hormone (bound to

proteins) have a half-life of 1 to 6 days.

9

Major endocrine glands, their secretions and disorders

The major endocrine glands include hypothalamus and pituitary (hypothalamo–hypophyseal system), thyroid, parathyroid, adrenal, pancreas, thymus, pineal gland and the gonads (ovary and testis) (Figure 3).

Pineal

Hypothalamo–hypophyseal system

Thyroid

Thymus

Adrenal

Pancreas

Ovary

Testis

Fig 3: Position of the major endocrine glands in the body

Hypothalamo–hypophyseal axis

For a long time the pituitary gland (hypophysis) was regarded to be the master gland of the body as it secretes hormones that control the secretion of other glands in the body. Then it was discovered that the pituitary itself is regulated by another gland, the hypothalamus, which secretes a set of regulatory hormones that act on the pituitary. Thus this hypothalamo–hypophyseal axis regulates the activity of various glands in the body (Figure 4). H

Hypothalamus

10

It is a part of the brain below the thalamus. It is an important connecting link between the nervous system and the endocrine system because it receives neural inputs from different regions of the brain and influences the secretions of the various hormones in the body through the pituitary gland. It integrates all the sensory inputs received by the brain from the body and acts as a regulatory centre for maintaining body temperature, osmotic balance, heart rate, respiratory rate, etc.

Releasing or inhibiting hormones Control and regulation of hormone

secretion Thyrotropin releasing hormone (TRH) Stimulates thyrotropin (TSH)

Growth hormone releasing hormone

(GHRH)

Stimulates growth hormone release

Growth hormone inhibiting hormone

(GHIH)

Inhibits growth hormone release

Prolactin releasing hormone (PRH) Stimulates prolactin release

Prolactin inhibiting hormone (PIH) or

dopamine

Inhibits prolactin release

Adrenocorticotropic hormone releasing

hormone (CRH)

Stimulates adrenocorticotropic hormone

release

Melanocyte stimulating hormone releasing

hormone (MSHRH)

Stimulates melanocyte stimulating hormone

release

Melanocyte stimulating hormone inhibiting

hormone (MSHIH)

Inhibits melanocyte stimulating hormones

release

11

Fig 4: Action of releasing and inhibitory hormones from the hypothalamus and hormones of the anterior pituitary gland

Hypothalamo–hypophyseal portal system

The hypothalamus secretes stimulatory (releasing) and inhibitory hormones or factors which stimulate or inhibit the release of hormones from the anterior lobe of the pituitary. These factors are synthesized by the neurosecretory cells of the hypothalamus and released on appropriate stimulation. These factors are not released in the general circulation but a special local network of blood vessels between the hypothalamus and hypophysis—the hypothalamo–hypophyseal portal system (Figure 5).

The hypothalamus receives blood supply from the superior hypophyseal arteries that form the primary capillary plexus in the hypothalamus which join to form the hypophyseal portal veins that branch again in the anterior lobe of the pituitary to form a secondary plexus of the hypophyseal system. The releasing or inhibitory factors released by the hypothalamus are directly brought to the hypophysis through this portal system so that they do not get diluted in the general circulation.

12

Fig 5: Hypothalamo–hypophyseal portal system

s

e

m

Neurohypophysis

Pars nervosa

Hypophysis (Pituitary)

The hypophysis or pituitary gland is connected to the hypoth

infundibulum.

The pituitary consists of two lobes, the anterior lobe or aden

lobe or neurohypophysis. The adenohypophysis has two part

upper pars tuberalis which forms a covering around the infun

has the lobe like pars nervosa and the infundibulum. During

intermediate lobe called the pars intermedia is present which

its cells get integrated into the pars distalis.

Primary capillary plexus

Pars distalis

Pars tuberalis

Adenohypophysis

Hypophyseal portal veins

Infundibulu

alam

ohy

s, th

dib

emb

is l

Hypothalamu

u

po

e

ul

r

os

Secondary capillary plexus

Median eminenc

s though a stalk, the

physis and the posterior

lower pars distalis and the

um. The neurohypophysis

yonic development a third

t in the adults but some of

13

Somatotroph

It consists of five types of cells that secrete seven types of hormones (Figure 6). These are:

Adenohypophysis

1. Somatotrophs that secrete the growth hormone (GH) or

Corticotroph

Lactotroph

Gonadotroph

Thyrotroph

2. Antidiuretic hormone (ADH) or vasopressin produced by the supraoptic nucleus.

1. Oxytocin

This region of pituitary does not synthesize any hormones. It stores and then secretes two hormones which are synthesized in the neurons of the hypothalamus. There are two sets of neurons in the hypothalamus, the supraoptic nucleus and paraventricular nucleus which synthesize hormones and convey them to the posterior pituitary through the nerve fibres of these neurons. These nerve fibres form the axon terminals in the posterior pituitary where these hormones are stored and released on appropriate stimulation. These two hormones are:

Neurohypophysis Fig 6: Cell types of the adenohypophysis

produced by the paraventricular nucleus.

3. Gonadotrophs secrete the follicle stimulating hormone (FSH) and the luteinizing hormone (LH). These two hormones together are known as gonadotropins because they stimulate the gonads to produce specific hormones.

5. Corticotrophs secrete adrenocorticotrophic hormone (ACTH) which stimulates the adrenal cortex to produce adrenocorticoids (cortisol, corticosterone, and aldosterone). Some corticotrophs are the remnants of the pars intermedia and they secrete the melanocyte stimulating hormone (MSH).

4. Lactotrophs secrete the hormone prolactin.

2. Thyrotrophs that secrete the thyroid stimulating hormone (thyrotropin)

somatotropin

14

Part of pituitary

Principal cell type Hormones Principal actions Target organs

Disorders

Somatotroph Growth

hormone (GH)

Growth of body cells especially of

bones of limbs, stimulates protein

synthesis and inhibits protein

breakdown, stimulates hydrolysis

of fats, retards use of blood

glucose for ATP production

(diabetogenic effect).

General Hyposecretion

Dwarfism—Reduced secretion of GH from the anterior

pituitary results in stunted growth so the person

remains a dwarf. In African Pygmies and Lévi-Lorain

dwarfs, however, the secretion of GH from the

hypothalamo-hypophyseal tract is normal but

Somatomedin C (a mediator of growth hormone

action) levels are low. Levels of GH reduce with age.

Hypersecretion

Gigantism—This occurs due to overactivity of the

somatotrophs or some tumors in this region of the

pituitary causes increased secretion of GH. If this

happens before adolescence (before the closure of

epiphyseal plates) the person is abnormally tall.

If this happens after adolescence the bones become

thicker and the soft tissue continues to grow. In his

condition, called acromegaly, the hands and feet

become greatly enlarged, the lower jaw protrudes

out, the forehead slants forwards, and the tongue

liver and kidneys also become enlarged.

Thyrotroph Thyrotropin or

thyroid

stimulating

hormone

(TSH)

Controls secretion of thyroid

hormones

Thyroid

gland

Adeno-

hypophys

is

Corticotroph Adrenocorticot

ropic hormone

(ACTH)

Controls secretion of adrenal

cortex hormones.

Adrenal

cortex

15

16

Lactotroph Prolactin (PRL) Along with other hormones

stimulates milk production,

participates in control of

reproduction, osmoregulation,

growth and metabolism

Mammary

glands

Follicle

stimulating

hormone

(FSH)

In males, stimulates

spermatogenesis. In females

stimulates growth of ovarian

follicles.

Gonads

Gonadotroph

Luteinizing

hormone (LH)

Or

Interstitial cell

stimulating

hormone

(ICSH)

In females, also causes secretion

of estrogen & proferone and

together with FSH, it triggers

ovulation, stimulates conversion of

ovarian follicles into corpus

luteum.

In males stimulates stimulation of

testosterone from interstitial cells

of Leydig.

Gonads

No hormones are

synthesized here. Its

hormones are

synthesized in

hypothalamus

Oxytocin (OT) Stimulates contraction of uterine

muscles during birth; initiates

ejection of milk.

Uterine

muscles and

mammary

glands

Neuro-

phypophy

sis

Antidiuretic

hormone

(ADH) or

vasopressin

Stimulates reabsorption of water

and reduction in urine output;

stimulates constriction of blood

vessels to increase blood pressure,

reduces sweat secretion from

sweat glands.

Kidney,

blood

vessels,

sweat

glands

Hyposecretion causes diabetes insipidus. Inability

of the posterior pituitary to secrete enough ADH can

be due to head injury, some infections or it may be

congenital. It can result in loss of water from the

body due to the formation of very dilute urine as

enough water is not reabsorbed by the kidney

tubules resulting in severe dehydration.

The thyroid gland is an H-shaped gland that lies over the trachea below the larynx with the right and left lateral lobes on either side of it. The lobes are connected by a mass of tissue, called the isthmus. The gland consists of microscopic spherical sacs called thyroid follicles. These contain a colloid, composed of the glycoprotein thyroglobulin bound to thyroid hormones triiodothyronine (T3) and tetraiodothyronine or thyroxine (T4), which fills most of the thyroid gland.

Thyroid gland

Blue arrow shows parafollicular or C-cells that secrete calcitonin which helps lower calcium levels. These C-cells are actually named for being "clear" (as it is lightly stained). Notice that they are in the interstitium and do not normally touch the follicles.

Source: Courtesy: http://www.kumc.edu/instruction/medicine/anatomy/histoweb/endo/endo.htm ©1996 The University of Kansas

Thyroid gland

Larynx

Trachea

Basement membrane

Colloidal secretion

Cuboidal epithelium

The simple cuboidal epithelium lining the follicles produce the hormones T3 and T4 which are stored in the follicles with a glycoprotein, thyroglobulin. Notice that the thyroid is the only gland to store its hormones extracellularly.

Colloidal secretion

Follicular cell

Parafollicular cells

Blood c

17

apillary

18

Thyroid

cell type

Hormone Principle actions Disorders

Follicular

cells

Triiodothyronine

(T3)

Thyroxine or

tetraiodothyronine

(T4)

Increases basal metabolic

rate, stimulates synthesis

of proteins, increases use

of glucose and fatty acids

for ATP production,

increases heart strength,

accelerates body growth

and contribute to the

development of nervous

system in the embryo.

Hypersecretion is called hyperthyroidism and hyposecretion is called hypothyroidism.

Hyperthyroidism (toxic goiter, thyrotoxicosis or Grave’s disease). Is caused by an

autoimmune disorder where antibodies bind to receptors to TSH mimicking its action in

stimulating the thyroid gland. These antibodies are called thyroid-stimulating

immunoglobulins.

It may also be caused by a tumour in the thyroid tissue. Symptoms of hyperthyroidism

include a high state of excitability, increased sweating, intolerance to heat, weight loss, hand

tremors, psychic disorders and protrusion of the eyeballs in most patients.

Hypothyroidism. There is a reduced secretion of thyroid hormones because of another type

of autoimmune disorder where antibodies destroy the secretory cells. It may also be caused

by a deficiency of iodine as it is needed for the synthesis of thyroid hormones. The gland

enlarges in order to increase the secretion of hormones. This state of enlarged thyroid gland

is called goiter. Hypothyroidism in adults causes myxedema where there is accumulation of

a gel-like fluid in the interstitial spaces. 0ther symptoms include swelling of the face,

bagginess under the eyes, sluggishness, reduced cardiac output, etc.

Hypothyroidism in fetal life, infancy or childhood causes a condition called cretinism. It could

be congenital or caused by iodine deficiency. Symptoms include mental retardation and

improper body growth.

Parafollicular

cells (C-

cells)

Calcitonin (CT)

Lowers blood levels of

ionic Ca2+ and phosphates

by inhibiting bone

resorption by osteoclasts

and stimulates uptake of

calcium and phosphates

into the bone matrix. This

effect is more

predominant in children

than in adults.

Parathyroid glands These are small masses of tissue, partially embedded in the posterior surface of the lateral lobes of the thyroid gland.

Oxyphil cells Chief cells

Parathyroid cells (Chief cell) in string-like arrangement on the right and large, clear oxyphil cells (whose function is unknown) to the left.

Thyroid gland

Larynx

Trachea

Parathyroid glands

Hormone and

source

Principal actions Disorders

Parathyroid

hormone (PTH)

from Chief cells

Increases blood Ca2+ and PO42+ levels.

Increases bone resorption by osteoclasts;

and promotes formation of calcitriol,

which increases rate of dietary Ca2+ and

Mg2+ absorption, decreases the excretion

of calcium from the kidneys.

Hypoparathyroidism occurs when the

parathyroid hormone is not secreted in

adequate amounts. This results in decrease in

Ca2+ ion concentration of blood; very low levels

of calcium result in tetany that could be fatal.

Hyperparathyroidism is increased secretion of

parathyroid hormone and results in an

increased plasma Ca2+ ion concentration due to

increased bone resorption. This results in

weakened bones, depressed peripheral and

central nervous system, muscle weakness,

constipation, lack of appetite and depressed

relaxation of the heart muscle during diastole.

Secondary hyperparathyroidism may be caused

by vitamin D deficiency where there is a

compensatory hyperactivity of the parathyroid

gland.

19

A pair of adrenal (supra-renal) glands are located, one on each side of the spinal cord, above each kidney. Each gland consists of an outer cortex and inner medulla. The cortex has three distinct layers—zona glomerulosa, zona fasciculata and zona reticularis, each secreting different types of steroids. Medulla as groups of large cells which secrete epinephrine and norepinephrine on sympathetic stimulation (that is why adrenal medulla is considered to be an extension of the sympathetic nervous system).

Adrenal glands

Capsule

Adrenal glands

Kidney

Adrenal cortex

Adrenal medulla

Medulla

Zona reticularis

Zona fasciculata

Zona glomerulosa

Source: Courtesy: http://www.kumc.edu/instruction/medicine/anatomy/histoweb/endo/endo.htm ©1996The University of Kansas

20

Gland part Cell type Hormone Principal action Target

organ

Disorders

Zona

glomerulosa

cells

Mineralocorticoid

s (mainly

aldosterone)

Controls electrolyte and water balance,

increases blood levels of Na+ and H2O,

decreases blood levels of K+ by

stimulating kidney tubules to reabsorb

more Na+, Cl– and water and less K+.

Promotes Na+ resorption and K+ and

HCO3- excretion in sweat glands. It also

stimulates Na+ resorption in the large

intestine.

Kidney Hyposecretion disorder is called hypoadrenalism or

Addison’s disease. This may be caused by atrophy of the

cortical cells due to an autoimmune disorder. It may also

be caused by tuberculous infection or cancer. It causes

reduced blood volume, hyponatremia, hyperkalemia,

reduced cardiac output, sluggishness, increased

susceptibility to any kind of stress and increased

pigmentation of the mucous membranes and skin.

Hypersecretion is called hyperadrenalism or Cushing’s

syndrome. It may be caused by an abnormal function of

the hypothalamus that causes hypersecretion of the

corticotrophin releasing hormone which is turn causes an

increased secretion of ACTH and cortisol. It may also be

due to an abnormally high secretion of ACTH from the

pituitary or hypersecretion of cortisol due to an adrenal

cortex adenoma. Symptoms include abnormal deposition of

fat in the thoracic and upper abdominal regions, edema,

acne, hirsuitism (due to increased levels of androgens).

Hypersecretion of only aldosterone from the zona

glomerulosa of the adrenal cortex caused by a tumour in

this region is known as Conn’s syndrome. It is

characterized by hypokalemia, hypernatremia, increased

blood volume. Muscle paralysis may occur due to

hyperkalemia (which interferes with normal transmission of

the action potential), It causes an reduced renin secretion

from the kidneys due to increased blood volume.

Cortex

Zona Glucocortiocoids Raises blood glucose level, promotes Liver,

21

fasciculata

cells

Cortisol (main),

corticosterone

gluconeogenesis in the liver and reduces

glucose utilization by cells, reduces

protein stores in all other cells of the

body, except liver cells and plasma,

promotes mobilization of fatty acids from

adipose tissue and enhances oxidation of

fatty acids in the cells, provides general

resistance to long term stress by blocking

inflammatory and allergic responses.

adipocytes

and other

body cells

Zona

reticularis

cells

Androgens

(main), e.g.

dihydroepiandros

terone (DHEA)

and

androstienedione

Assists in early growth of axillary and

pubic hairs in both sexes; in females, it

contributes to libido and is a source of

estrogen after menopause

Gonads Hypersecretion of androgens from the zona reticularis

because of a tumour in this part of the adrenal cortex

causes the adrenogenital syndrome. It causes

masculinization of the body. If it occurs in a female there is

a development of male characteristics such as a beard, a

deeper voice, deposition of proteins in the muscles,

baldness, etc. If it occurs in a prepubertal male it causes

precocious development of secondary sexual characters.

Medulla Chromaffin

cells

Epinephrine

(adrenaline)

Norepinephrine

(nor-adrenaline)

Stimulates elevation of blood glucose by

conversion of liver glycogen to glucose;

raises blood pressure; accelerates the

rate and force of heart beat; causes

constriction of skin and visceral

capillaries; causes dilation of vessels of

heart and skeletal muscles; increases

lipid breakdown, oxygen consumption,

erection of hair, dilation of pupils; initiate

stress response

Skeletal

muscles,

cardiac

muscles,

smooth

muscles,

blood

vessels, fat

cells

22

The pancreas is both an endocrine and exocrine gland. It is a flattened organ, about 12.5–15 cm long, located in the curve of the duodenum. Roughly 99% of pancreatic cells are exocrine present in clusters called acini. Interspersed among them are a group of endocrine cells forming lobules known as pancreatic islets or Islets of Langerhans. These islets contain four types of cells— alpha (α), beta (β), delta (δ), and F cells.

Pancreatic islets

23

Types of cells in the Islet of Langerhans

Alpha cell

Beta cell

F cell

Pancreas

Capillary

Delta cell

24

Cell type Hormone Principal action Target organ Disorders

Alpha cells

(α cells)

Glucagon

Causes lypolysis

• Accelerates breakdown of glycogen into glucose

in liver.

• Promotes conversion of other nutrients, such as

amino acids and lactic acid, into glucose in the

liver (gluconeogenesis).

• Enhances the release of glucose into blood.

Liver adipose

tissue

Beta cells

(β cells)

Insulin • Stimulates glucose transport from blood to

muscles and adipose cells, and stimulates liver

to take up glucose.

• Inhibits gluconeogenesis in the liver.

• Promotes both oxidation and conversion of

glucose into glycogen in liver and muscle cells.

• Inhibits metabolic breakdown of stored glycogen

in liver and muscle cells.

• Promotes synthesis of fats from glucose by

adipose tissue and also inhibits metabolic

breakdown of fat.

• Promotes uptake of amino acids by liver and

muscle cells, and stimulates protein synthesis

while inhibiting protein breakdown.

Liver, muscle,

adipose tissue, and

body cells

Delta cells

(δ cells)

Somatostatin (is a

paracrine agent)

Inhibits secretion of glucagon and insulin; reduces

motility of stomach, duodenum and gall bladder;

reduces secretion and absorption in the digestive

tract.

Pancreas (α and β

cells),

gastrointestinal

tract

F cells Pancreatic

polypeptide

(is a paracrine agent)

Inhibits somatostatin secretion, gall bladder

contraction and secretion of pancreatic digestive

enzymes.

Pancreas, gall

bladder

Hypersecretion of insulin is

called hyperinsulinism. It

may be caused by an

adenoma of an Islet of

Langerhans. It results in

hypoglycemia (reduced

blood glucose levels) which

could be fatal.

Hyposecretion of insulin or

hypoinsulinism causes

diabetes mellitus (Type I).

In Type II diabetes mellitus

the amount of insulin

secreted by pancreatic β

cells is normal but the

response of the cells is not

(insulin resistance).

Diabetes mellitus causes

hyperglycemia, glycosuria

(glucose in urine) polyuria

(increased urine output),

tissue injury, increased

metabolism of fat,

ketoacidosis and depletion

of body proteins.

25

Gonads and placenta

The testis in males and ovaries in females secrete sex hormones during puberty. These hormones are steroids and responsible for controlling various secondary sexual characters during puberty. The placenta also releases some hormones that are responsible for the maintenance and certain changes during pregnancy.

he testis in males and ovaries in females secrete sex hormones during puberty. These hormones are steroids and responsible for controlling various secondary sexual characters during puberty. The placenta also releases some hormones that are responsible for the maintenance and certain changes during pregnancy.

Ovary Testis Placenta

Ovarian follicle Corpus luteum Testis

The Graafian follicle is identified by the large antrum (A) and the cumulus oophorous (arrow) that surrounds the actual oocyte and projects into the antrum.

Source: Courtesy: http://www.kumc.edu/instruction/medicine/anatomy/histoweb/female/female.htm ©1996 The University of Kansas

Progesterone from the corpus luteum maintains the uterus for implantation. Granulosa luteal cells (GL) and theca luteal cells (TL).

Interstitial cells of Leydig

Seminiferous tubule

Sperms in different stages of development

26

Gland type

and part

Hormones Principal action Disorders

Ovary

Ovarian follicle Estrogen (estradiol

and estrone)

Stimulates the development and maintenance

of female sexual characteristics such as high

pitch, female voice and female pattern and

distribution of body hair at puberty.

Together with gonadotropic hormones of the

anterior pituitary gland they also regulate

menstrual cycle and development of

secondary sex organs.

Hypogonadism: when there is reduced estrogen secretion because

of poorly formed ovaries or genetically abnormal ovaries female

eunuchism occurs. The female secondary sexual characteristics fail

to develop and there is a prolonged growth of bones. The ovarian

cycles are irregular or there may be complete amenorrhoea.

Hypersecretion of estrogens: may occur in case of a granulosa cell

tumour which usually occurs after menopause. Symptoms include

hypertrophy of the endometrium and irregular bleeding.

Corpus luteum Progesterone and

estrogen

Progesterone prepares and maintains the

uterine lining for pregnancy, stimulates

mucosal lining of the fallopian tubes to

secrete a nutrient-rich fluid, prevents the

uterine myometrium from undergoing

contractions. Prepares the breast for milk

secretion. Estrogen stimulates uterine lining

for implantation to maintain pregnancy,

prepares the mammary glands for lactation

and regulates oogenesis.

Relaxin Facilitates accommodation of the growing

fetus. Relaxes pubic symphysis and helps

dilate uterine cervix near the end of

pregnancy.

Inhibin Regulates oogenesis by inhibiting FSH and

GnRH secretion.

Testis

Interstitial cells Testosterone Stimulates the descent of testis and male Hypogonadism: where there is a loss of testes or if there is a

27

of Leydig pattern of development (before birth);

stimulates development and maintenance of

male sexual characteristics and expression of

male characteristics such as beard,

moustache and low-pitch voice; stimulates

spermatogenesis, growth spurt, protein

synthesis and muscle development, bone

growth, stimulate secretion of erythropoietin

from the kidneys; increases basal

metabolism.

reduced secretion of GnRH from the hypothalamus (adipose genital

syndrome or Fröhlich’s syndrome or hypothalamic eunuchism). In

the absence of testosterone in an adult some of the secondary

sexual characteristics are lost. In a child these characteristics fail to

develop.

Hypergonadism: refers to an increased secretion of testosterone

due to tumour of Leydig cells. This causes an abnormally increased

muscle growth, reduced height (as the epiphyseal plates close

early) and excessive development of male sexual characteristics.

Sertoli cells Inhibin Regulates spermatogenesis by inhibiting FSH

secretion.

Placenta

Human chorionic

gonadotropin

(HCG)

Stimulates progesterone release from the

corpus luteum and maintains it. It has an

interstitial cell stimulating effect in a male

fetus. Simulates mammary gland growth

during pregnancy. Has weak growth hormone

like effects. Decreases insulin sensitivity and

glucose utilization by the mother’s cells so

that glucose is made available to the fetus. It

also mobilizes fatty acids from mother’s fat

stores.

or

Human placental

lactogen

Thymus

The thymus is located behind the sternum. It consists of two lobes

separated from one another by a connective tissue capsule.

Extensions of this capsule penetrate in the form of septa or

trabeculae to divide each lobe into lobules. Each lobule has a

lighter staining central medulla surrounded by a darkly staining

outer cortex. The cortex contains T cells which proliferate and

mature in the thymus; dendritic cells that assist the maturing T

cells and epithelial cells with long processes form a framework for

the maturing T cells. The medulla consists of more mature T cells,

epithelial cells and macrophages. Clusters of flattened degenerate

epithelial cells are arranged in concentric layers called Hassall’s

(thymic) corpuscles. In infants, the thymus is large but it starts

degenerating after puberty and is almost absent in old age.

Thymus Hormones Princip

Thymosin, thymic humoral factor,

thymic factor, thymopoietin

Promot

matura

lympho

Thymus

Source: http://www.cytochemistry.net/microanatomy/immune_system/lymphoid_tissues.htm© copyright 1998 Gwen V. Childs, Ph.D. URL Address: http://cellbio.utmb.edu/microanatomy/ Gwen V. Childs, Ph.D., WebMistress gvchilds@utmb.edu

al action

e the proliferation and

tion of T-cells (derived from

cytes)

28

Pineal gland

It is a small endocrine gland attached to the roof of the third ventricle of the brain at the midline. It is covered by a capsule formed by pia mater and consists of masses of neuroglia and secretory cells called pinealocytes. It secretes the hormone melatonin, which is believed to help in maintaining the biological clock, as it is produced when no light stimulus is present and its production ceases when eye receives light stimulus.

Cerebral cortex

Pineal gland

Hypothalamus

Pituitary

Pineal gland Hormones Principal action

Melatonin Involved with the setting of the

biological clock in the body.

Controls seasonal fertility in some

animals.

Other endocrine tissues

Some tissues other than those described already, contain endocrine cells which secrete hormones. Along with these hormones some growth factors are also produced which stimulate cell growth and division.

29

Production site Hormone or

growth factor

Principal action

Gastrointestinal tract

G-cells of the stomach

Gastrin

Promotes secretion of gastric juice and increases motility

of the stomach.

Glucose-dependent

insulinotropic peptide

(GIP)

Stimulates release of insulin by pancreatic β cells, inhibits

gastric secretion.

Secretin Stimulates secretion of pancreatic juice rich in HCO3– ions

and bile; reduces gastric secretion and motility.

Cholecystokinin

(CCK)

Stimulates secretion of pancreatic juice rich in enzymes,

release of bile from the gall bladder and brings about the

feeling of fullness after eating.

Enteroendocrine cells of

the duodenum

Vasoactive intestinal

polypeptide (VIP)

Inhibits gastric secretion and motility

Oxyntic cells of the

stomach and cells of

the intestine

Ghrelin Stimulates food intake

Liver Angiotensinogen gets

converted to

angiotensin I which

gets converted to

angiotensin II

Causes vasoconstriction, enhances reabsorption of sodium

and chloride ions and water, stimulates the release of

aldosterone from adrenal cortex which further stimulates

reabsorption of sodium and chloride ions from the kidney

tubules. All this results in increased blood volume and

blood pressure.

Erythropoetin (EPO) Increases rate of red blood cell formation. Kidneys

Calcitriol (active

vitamin D)

Aids in the absorption of dietary calcium and phosphorus.

Heart Atrial natriuretic

peptide (ANP)

Decreases blood pressure and blood volume by

stimulating the excretion of Na+ ions from the kidney

tubules.

Adipose tissue Leptin Suppresses appetite, stimulates the release of

corticotropin releasing hormone that decreases food

intake, increases sympathetic activity resulting in an

increased metabolic rate and energy expenditure,

suppresses the release of appetite stimulators from the

hypothalamus.

Submaxillary salivary

gland

Epidermal growth

factor (EGF)

Stimulates proliferation of epithelial cells, fibroblasts,

neurons and astrocytes; suppresses some cancer cells and

30

secretion of gastric juice by the stomach.

Nerve growth factor

(NGF)

Stimulates the growth of ganglia in embryonic life,

maintains sympathetic nervous system, and stimulates

differentiation of neurons.

Blood platelets Platelet-derived

growth factor (PGF)

Found in blood; stimulates proliferation of neuroglial cells,

smooth muscle fibres, and fibroblasts; may have a role in

wound healing; may contribute to the development or

artherosclerosis.

Pituitary and brain Fibroblast growth

factor (FGF)

Stimulates proliferation of many cells derived from

embryonic mesoderm (fibroblasts, adrenocortical cells,

smooth muscle fibers, chondrocytes and endothelial cells);

stimulates cell migration and growth and production of

fibronectin (an adhesion protein).

Normal and tumor

cells

Tumor angiogenesis

factor (TAFs)

Stimulates growth of new capillaries, organ regeneration

and wound healing.

Various cells Transforming growth

factors

Some have activities similar to epidermal growth factor,

others inhibit proliferation of many cell types.

31