Pituitary Hormones and Their Control by the Hypothalamus

Physiological Functions of Growth Hormone

All

the major anterior pituitary hormones, except for growth hormone, exert their principal effects by stimulating target glands. Growth hormone does not function through a target gland. Its exerts its effects directly on all or almost all tissues of the body.

Growth Hormone Promotes Growth of Many Body Tissues

Growth hormone, also called Somatotropic hormone or Somatotropin hormone Small protein molecule contains191 amino acids in a single chain Molecular weight: 22,005. It causes growth of all tissues of the body that are capable of growing. It promotes incr sizes of the cells & mitosis, and specific differentiation of certain types of cells

STRUCTURE
2

intrachain disulfide bridges. Structure resembles that of prolactin. In anterior pituitary there are three types of cells. Acidophills, Basophils Chromophobes

 Acidophills

secrete G.H & prolactin. these cells have affinity for asidic dyes. Basophils secrete TSH, ACTH, FSH& LH these cells have affinity for basic dyes. Chromophobes are cells which are inactive, dont take any stain, & dont secrete.

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 is not direct It is through somatomedins,

Somatomedins,
Which are small peptides with mol.wt b/w 5000-10000. G.H acts on liver & other organs (skeleton muscle & kidneys) to form somatomedin.

Somatomedins

are of different types Imp is somatomedin C also called insulin like growth factor 1.

 Insulin-like

growth factor 1(IGF-1) OR Somatomedin C causes growth after birth Insulin-like growth factor II (IGF-II) causes growth of fetus before birth Growth hormone has half time in blood is less than 20 minutes Somatomedin C has half time of about 20 hours

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 length 2. AFTER ADULT AGE Increased thickness by osteoblasts

FUNCTION OF GROWTH HORMONE

PROTEIN

Promotes anabolism Decreased catabolism FAT KETOGENIC CARBOHYDRATE DIABETOGENIC

Growth Hormone Has Several Metabolic Effects

Growth hormone has multiple specific metabolic effects: (1) Incr rate of protein synthesis in most cells of the body; (2) Incr mobilization of fatty acids from adipose tissue, incr free fatty acids in the blood, incr use of fatty acids for energy; (3) Decr rate of glucose utilization throughout the body. Growth hormone enhances body protein, uses up fat stores, and conserves carbohydrates.,

Actions on protien metabolism

It is protien anabolic hormone. It stimulates protien synthesis by increasing transport of A.Acids into the cell. It stimulates gene transcription (i.e. inc formation of mRNA) also gene translation (i.e. acts on mRNA to incr protien synthesis). G.H inhibits protien catabolism. It produces +ve nitrogen balance (anabolic) it decreases plasma level of blood urea nitrogen

Actions on carbohydrates metabolism

G.H moderately decr glucose utilization in the cell. Some glucose is deposited as glycogen & because of decr utilization further entry of glucose in cell is decr. Because of incr fatty acids mobilization & oxidation excess of acetyl Co A is available & this perhaps inhibits glucose utilization in cells.

Because of decr glucose uptake hyperglycemia under effect of G.H, blood glucose incr it stimulates beta cells to secrete more insulin. Due to persistant hyperglycemia, due to incr G.H burning out of beta cells of pancrease pituitary diabetes. In pituitary diabetes glucose utilization is moderately dec but in diabetes mellitus grossly dec. Pituitary diabetes is more resistant to insulin. So G.H has diabetogenic effect.

Actions on fat metabolism

It utilizes fat. It mobilizes fat from adipose tissue. These fatty acids are oxidized excess of acetyl Co A. It can be used for energy & also converted into aceto 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 in blood fatty liver).for actions of of growth hormone, adequate amounts of insulin & CHO are required.

Other actions
G.H

stimulates erythripoiesis. Produces +ve phosphorus balance. It incr Ca absorption from the intestine 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.

Control of secretion of growth hormone

Hypothalamus

control growth hormone secretion through 2 hormones: i)Growth hormone releasing hormone(GHRH) Ii)Growth hormone inhibitary hormone(GHIH)/SOMATOSTATIN.

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 stimulate G.H secretion. Stressfull conditions, trauma,excitement stimulate G.H secretion.

 Deep

sleep/slow wave sleep (NREM sleep) 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.

Factors which inhibits GH secretion

Hyperglycemia

Incr

plasma free fatty acids Cortisol GH through ve feedback. REM sleep.

REGULATION OF GROWTH HORMONE SECRETION

Effect of blood glucose level on GH

GHRH is produced from neurons in ventromedial nucleus of hypothalamus. Here satiety center is present which has glucostat 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 appetite inc food intake, also release of GH. (Satiety center stimulated but hunger center inhibited in hypoglycemia).

Abnormalities of Growth Hormone Secretion Panhypopituitarism. Decr secretion of all the anterior pituitary hormones. 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.

HYPOPITUITARISM
Hypopituitarism

in children is called dwarfism. There is deficiency of anterior pituitary hormones including G.H. Due to growth hormone deficiency growth of the child is retarded.but growth of different parts of the body is proportinate. A child of 10 years appear to be 4-5 years age.

There is no adrenocortical & thyroid deficiency. Although there is less ACTH, TSH, but b/c of small size body less requirement of these hormones. In most of these dwarf there is impairment of sexual function b/c of less FSH & LH. BUT in 1/3 of dwarfs there are normal sexual functions& they are able to reproduce. In some of the dawarf there are adequate secretion of GH but defect in GH receptors. So receptors are unresponsive & these are called Larones dwarf.

 In

some of the dwarf GH secretion are normal or incresed but there are deficiency of somatomedin C. These are called lorian dwarf. One type of dwarf in which there is sexual retardation is called Frohlic syndrome. There is no mental retardation in dwarfs.

Simonds disease /panhypopituitarism in adults

In

adults when there is hypopituitarism there will be adrenocortical & thyroid deficiency b/c of ACTH & TSH deficiency: Hypoglycemia Hypotension Hyponatremia Intolerance to cold, Weigh gain

 Because

of deficiency of FSH & LH, there is atrophy of primary sex organs, i.e. gonads(testes, ovary). Sexual retardation: In female disturbance of mensural cycle. Growth of tissue is retarted b/c of decr GH.

Sheehans syndrome
Seen

in female It is due to ischemic neurons of pituitary resulting from excessive post partal hemorrhage. Features of hypopituitarism.

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 by growth, adrenocorticotropic, adrenocortical, and thyroid hormones) lost all sexual functions. Treatment : Administeration of adrenocortical and thyroid hormones.

hyperpituitarism
There

is an acidophil tumor. They secrete GH & Prolactin. There is excess of GH secretion. It occurs in children before adolescence, it is called gigantism. There is inc GH before adolesence i.e. inc GH before union of epiphysis with shaft in long bones, so length of bones increases very much.

Height of the individual may b 8-9 ft. Ultimately in most of these individual develop hypopituitarism b/c pituitary tumor destroys the pituitary tissue. In gigantism there is osteo-arthritis. Some develop DM(GH is diabetogenic). In female with gigantism, there is lactation without pregnency due to prolactin secretion.

 In

these pt there is also local effects b/c of pituitary tumor & these effects are Headache Visual disturbances Bitemporal hemianopia(pituitary tumor effects the center of the optic chiasma where there is crossing of nasal fibers from retina so they will be destroyed.

 Deficiency

of pituitary hormones usually causes death in early adulthood. Once gigantism is diagnosed, further effects can be blocked by microsurgical removal of the tumor or by irradiation of the pituitary gland.

Acromegaly
It is the excess of GH after adolescence when the epiphysis of long bones have united. acromegaly means enlargment of peripheral parts. Due to excess of GH thickness of bones inc very much as bones cant grow in length. This bone growth effects small bones of hands, feet, & other bones including skull bones, vertebrae, supraorbital ridges, nasal bones & also jaw bones.

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.

 b/c

of excessive growth of these bones there are specific features. Size of hand & feet is twice normal(spade like hands) Forward protrusion of lower jaw (prognathism) there is slanting forward of supraorbital ridges. Size of nose is twice normal

 Typically

an acromegalic patient resembles Gorilla Hands reaching the knees, huntched back(kyphosis) Prognathism.

Possible Role of Decreased Growth Hormone Secretion 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 appearance of a person aged 65. The aged appearance seems to result mainly from decreased protein deposition in most tissues of the body and increased fat deposition in its place. The physical and physiological effects are increased wrinkling of the skin, diminished rates of function of some of the organs, and diminished muscle mass and strength.

It is possible that some of the normal aging effects result from diminished growth hormone secretion. In fact, multiple tests of growth hormone therapy in older people have demonstrated three impt effects that suggest antiaging actions: (1) incr protein deposition in the body, esp in the muscles; (2) decreased fat deposits; (3) a feeling of increased energy.