growth hormone by dr. sadia zafar

8/22/2019 Growth Hormone by Dr. Sadia Zafar

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Pituitary Hormones and

TheirControl by the

Hypothalamus


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Physiological Functions

of Growth Hormone

All the major anterior pituitaryhormones, except for growthhormone, exert their principal effects

by stimulating target glands.

Growth hormone does not functionthrough a target gland.

Its exerts its effects directly on all oralmost all tissues of the body.


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Growth Hormone Promotes Growth

of Many Body Tissues

Growth hormone, also called

Somatotropic hormone or

Somatotropin hormone

Small protein molecule contains191 amino acidsin a single chain

Molecular weight: 22,005.

It causes growth of all tissues of the body thatare capable of growing.

It promotes incr sizes of the cells & mitosis,and specific differentiation of certain types ofcells


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STRUCTURE

2 intrachain disulfide bridges.

Structure resembles that of prolactin.

In anterior pituitary there are threetypes of cells.

Acidophills,

BasophilsChromophobes


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Acidophills secrete G.H & prolactin.

these cells have affinity for asidicdyes.

Basophils secrete TSH, ACTH, FSH&

LH these cells have affinity for basicdyes.

Chromophobes are cells which are

inactive, dont take any stain, & dontsecrete.


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ACTIONS

G.H promotes growth of the body.

Promotes growth of all the tissues.

Increase no & size of cells. Increase mitosis.

Stimulates growth of cartilage & bone

Actions of growth hormone on bones isnot direct

It is through somatomedins,


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Somatomedins,

Which are small peptides with mol.wtb/w 5000-10000.

G.H acts on liver & other organs

(skeleton muscle & kidneys) to formsomatomedin.

Somatomedins are of different types

Imp is somatomedin C also calledinsulin like growth factor 1.


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Insulin-like growth factor 1(IGF-1)

OR Somatomedin C causes growthafter birth

Insulin-like growth factor II (IGF-II)causes growth of fetus before birth

Growth hormone has half time inblood is less than 20 minutes

Somatomedin C has half time ofabout 20 hours


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BONE AND CARTILAGE

GROWTH

G.H through somatomedins stimulates chondrocytes &

osteocytes

to lay down chondriatin sulphate & collagen &then Ca+ salts are deposited in bone matrix.

MECHANISM

1. BEFORE ADULT AGE

new cartilage at epiphyseal end so

increased length2. AFTER ADULT AGE

Increased thickness by osteoblasts


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FUNCTION OF GROWTH

HORMONE

PROTEIN

Promotes anabolism

Decreased catabolismFAT

KETOGENIC

CARBOHYDRATEDIABETOGENIC


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Growth Hormone Has Several

Metabolic Effects Growth hormone has multiple specific metabolic

effects:

(1) Incr rate of protein synthesis in most cells ofthe body;

(2) Incr mobilization of fatty acids from adiposetissue,

incr free fatty acids in the blood,

incr use of fatty acids for energy;

(3) Decr rate of glucose utilization throughout thebody.

Growth hormone enhances body protein, uses upfat stores, and conserves carbohydrates.,


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Actions on protien metabolism

It is protien anabolic hormone. It stimulates protien synthesis by

increasing transport of A.Acids into thecell.

It stimulates gene transcription (i.e. incformation of mRNA) also gene translation(i.e. acts on mRNA to incr protiensynthesis).

G.H inhibits protien catabolism. It produces +ve nitrogen balance

(anabolic) it decreases plasma level ofblood urea nitrogen


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Actions on carbohydrates

metabolism G.H moderately decr glucose utilization

in the cell. Some glucose is deposited as glycogen &

because of decr utilization further entryof glucose in cell is decr.

Because of incr fatty acids mobilization &oxidation excess of acetyl Co A isavailable & this perhaps inhibits glucose

utilization in cells.


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Because of decr glucose uptakehyperglycemia under effect of G.H, bloodglucose incr it stimulates beta cells to secretemore insulin.

Due to persistant hyperglycemia, due to incrG.H burning out of beta cells of pancreasepituitary diabetes.

In pituitary diabetes glucose utilization is

moderately dec but in diabetes mellitus grosslydec.

Pituitary diabetes is more resistant to insulin.

So G.H has diabetogenic effect.


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Actions on fat metabolism

It utilizes fat.

It mobilizes fat from adipose tissue.

These fatty acids are oxidized excess of acetylCo A.

It can be used for energy & also converted intoaceto acetic acid( ketone body)

So growth hormone has ketogenic effect.

Growth hormone produces fatty liver (i.e. free

fatty acids are mobilized inc fatty acids level inblood fatty liver).for actions of of growthhormone, adequate amounts of insulin & CHO arerequired.


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Other actions

G.H stimulates erythripoiesis.

Produces +ve phosphorus balance.

It incr Ca absorption from theintestine

It decr Na & k excretion in urine.

G.H prevents aging process.G.H levels in adult is about 3ng/ml.

In children above 5 ng/ml or more.


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Control of secretion of growth

hormone

Hypothalamus control growthhormone secretion through 2hormones:

i)Growth hormone releasinghormone(GHRH)

Ii)Growth hormone inhibitaryhormone(GHIH)/SOMATOSTATIN.


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Substances which stimulates GH

secretion. Deficiency of energy substrate seen in hypoglycemia, starvation,

severe protien deficiency, decr fatty acid in blood, exercise. Inc level of certain amino acids including

arginine, lysine, leucine levels stimulateG.H secretion. Stressfull conditions, trauma,excitement

stimulate G.H secretion.


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Deep sleep/slow wave sleep (NREMsleep) stimulates G.H secretion

Certain drugs can also stimulate GH

secretion e.g. L.Dopa, Apomorphine,serotonin,

Catecholamines, testosterone &

estrogen also do the same.Gluocagon also stimulate GH

secretion.


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Factors which inhibits GH secretion

Hyperglycemia

Incr plasma free fatty acids

CortisolGH through ve feedback.

REM sleep.


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REGULATION OF GROWTH

HORMONE SECRETION


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Effect of blood glucose level on GH

GHRH is produced from neurons in ventro-medial nucleus of hypothalamus.

Here satiety center is present which hasglucostat cell & there activity depends on

their glucose utilization. These cells require insulin for glucose

uptake. If insulin is there & there is hypoglycemia

they would not be active inc appetiteinc food intake, also release of GH.(Satiety center stimulated but hungercenter inhibited in hypoglycemia).


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Abnormalities of Growth

Hormone Secretion

Panhypopituitarism.

Decr secretion of all the anterior pituitaryhormones.

Decrease in secretion may be congenital,or it may occur suddenly or slowly at any

time during life. Most often resulting from a pituitary tumor

that destroys the pituitary gland.


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HYPOPITUITARISM

Hypopituitarism in children is calleddwarfism. There is deficiency ofanterior pituitary hormones including

G.H.

Due to growth hormone deficiencygrowth of the child is retarded.but

growth of different parts of the bodyis proportinate.

A child of 10 years appear to be 4-5

years age.


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There is no adrenocortical & thyroid deficiency.

Although there is less ACTH, TSH, but b/c ofsmall size body less requirement of thesehormones.

In most of these dwarf there is impairment ofsexual function b/c of less FSH & LH.

BUT in 1/3 of dwarfs there are normal sexualfunctions& they are able to reproduce.

In some of the dawarf there are adequatesecretion of GH but defect in GH receptors.

So receptors are unresponsive & these are calledLarones dwarf.


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In some of the dwarf GH secretionare normal or incresed but there aredeficiency of somatomedin C.

These are called lorian dwarf.

One type of dwarf in which there issexual retardation is called Frohlic

syndrome.

There is no mental retardation indwarfs.


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Simonds disease

/panhypopituitarism in adults

In adults when there ishypopituitarism there will beadrenocortical & thyroid deficiency

b/c of ACTH & TSH deficiency:

Hypoglycemia

Hypotension

Hyponatremia

Intolerance to cold,

Weigh gain


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Because of deficiency of FSH & LH,there is atrophy of primary sexorgans, i.e. gonads(testes, ovary).

Sexual retardation:

In female disturbance of mensuralcycle.

Growth of tissue is retarted b/c ofdecr GH.


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Sheehans syndrome

Seen in female

It is due to ischemic neurons ofpituitary resulting from excessivepost partal hemorrhage.

Features of hypopituitarism.


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The general effects of adult panhypopituitarism are (1) hypothyroidism, (2) depressed production of glucocorticoids by the adrenal

glands, (3) suppressed secretion of the gonadotropic hormones so

that sexual functions are lost. Clinical picture Lethargic person (from lack of thyroid hormones)

gaining weight (because of lack of fat mobilization bygrowth, adrenocorticotropic, adrenocortical, and thyroidhormones)

lost all sexual functions. Treatment : Administeration of adrenocortical and thyroid hormones.


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hyperpituitarism

There is an acidophil tumor.

They secrete GH & Prolactin.

There is excess of GH secretion.

It occurs in children beforeadolescence, it is called gigantism.

There is inc GH before adolesence

i.e. inc GH before union of epiphysiswith shaft in long bones, so length ofbones increases very much.


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Height of the individual may b 8-9 ft.

Ultimately in most of these individualdevelop hypopituitarism b/c pituitarytumor destroys the pituitary tissue.

In gigantism there is osteo-arthritis.

Some develop DM(GH is diabetogenic).

In female with gigantism, there islactation without pregnency due to

prolactin secretion.


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In these pt there is also local effectsb/c of pituitary tumor & these effectsare

Headache

Visual disturbances

Bitemporal hemianopia(pituitarytumor effects the center of the opticchiasma where there is crossing ofnasal fibers from retina so they will

be destroyed.


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Deficiency of pituitary hormonesusually causes death in earlyadulthood.

Once gigantism is diagnosed, furthereffects can be blocked by

microsurgical removal of the tumoror by irradiation of the pituitarygland.


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Acromegaly

It is the excess of GH after adolescencewhen the epiphysis of long bones haveunited.

acromegaly means enlargment of

peripheral parts. Due to excess of GH thickness of bones

inc very much as bones cant grow inlength.

This bone growth effects small bones ofhands, feet, & other bones including skullbones, vertebrae, supraorbital ridges,nasal bones & also jaw bones.


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Some may develop DM. Lactation without pregnency in female. Local effects due to pituitary tumors: Headache Visual disturbances (bitemporal

hemianopia) Also enlargement of soft tissue e.g. Tounge Liver Kidneys.


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b/c of excessive growth of thesebones there are specific features.

Size of hand & feet is twice

normal(spade like hands)Forward protrusion of lower jaw

(prognathism)

there is slanting forward ofsupraorbital ridges.

Size of nose is twice normal
http://findmeacure.com/2011/01/30/acromegaly/acromegaly/http://findmeacure.com/2011/01/30/acromegaly/acromegaly/


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http://findmeacure.com/2011/01/30/acromegaly/acromegaly/http://findmeacure.com/2011/01/30/acromegaly/acromegaly/


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Typically an acromegalic patientresembles Gorilla

Hands reaching the knees,

huntched back(kyphosis)

Prognathism.


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Possible Role of Decreased Growth HormoneSecretion

in Causing Changes Associated with Aging In people who have lost the ability to secrete growth

hormone, some features of the aging process accelerate. For instance, a 50-year-old person who has been without

growth hormone for many years may have the appearanceof a person aged 65.

The aged appearance seems to result mainly fromdecreased protein deposition in most tissues of the bodyand increased fat deposition in its place.

The physical and physiological effects are increasedwrinkling of the skin, diminished rates of function of someof the organs, and diminished muscle mass and strength.


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It is possible that some of the normalaging effects result from diminishedgrowth hormone secretion.

In fact, multiple tests of growth hormone

therapy in older people havedemonstrated three impt effects thatsuggest antiaging actions:

(1) incr protein deposition in the body, espin the muscles;

(2) decreased fat deposits; (3) a feeling of increased energy.

growth hormone by dr. sadia zafar

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