ENDOCRINE GLANDS

The different activities of the body are regulated by 2 main systems:-

1. The nervous system. 2. The endocrine system.

The nervous system: is concerned with regulation of metabolic activities and secretions of glands. It is a rapid control system.

The endocrine system: is concerned with regulation of metabolic functions. It is a slow control system. What is meant by the endocrine system?

It is a system of ductless glands, which differs from other types of glands such as the salivary glands in that their secretions which are called hormones enter the blood stream directly which carries them to different tissues to produce their effects. What is a hormone ?

It is a chemical substance secreted into the blood stream by endocrine glands to act on distant organs called effector organs. Properties of hormones:

They are secreted in very small amounts. So, their blood and tissue concentrations are very low. They do not act on the organs secreting them (endocrine glands) but act on distant organs (effector organs). Hormones may act on a specific effector organ e.g. thyrotrophic hormone (TSH) of the anterior pituitary acts specifically on the thyroid gland, or hormones may act on the body as a whole e. g. growth hormone (GH) of the anterior pituitary. Hormones act on the target organ by changing the rate of biochemical reactions in that organ. This effect persists for a longer period even after the hormone which produced it becomes inactivated.

Difference between a hormone and an enzyme:

Hormone Enzyme Some hormones are proteins, some are amino acids and some are steroids. Hormones act on distant organs and not on those secreting them. Hormones are continually secreted, inactivated or excreted.

All enzymes are proteins.

Enzymes act in the same tissues forming them. Enzymes catalyze biochemical reactions without being destroyed or excreted.

Chemical nature of hormones: Hormones may be derived from:

(1) Amino acids: e.g.

Tryptophan serotonin and melatonin.

Tyrosine T4 (thyroxine) and T3 (triiodothyronine). (Thyroid hormones)

Catecholamines (e.g. Adrenaline and Noradrenaline.) (Hormones of the adrenal medulla) (2) Peptides and proteins: e.g.

All pituitary hormones are either peptides or proteins. The pancreatic hormones insulin and glucagon (peptides).

(3) Steroids in nature : e.g.

Adrenocortical hormones (cortisol). Sex hormones (testosterone).

The plasma level of a hormone depends upon 2 factors: 1- The rate of hormone secretion by the endocrine gland :

rate of secretion plasma hormone level (and vice versa) . N.B. Some hormones may show daily variation in the rate of secretion known as the circadian rhythm . 2- The rate of hormone inactivation and excretion:

rate of inactivation plasma hormone level (and vice versa). N.B. Inactivation may occur in the effector organ or in the liver, or may be excreted by the kidney.

Mechanism of Action of Hormones: Hormones change the activity of the effector organs by changing the

rate of enzymatically catalyzed reactions in them. This may be the result of:

(1) lncreased rate of enzyme synthesis increased enzyme concentration. lt is a slow response. e.g. Steroid hormones.

N.B. The rate of a biochemical reaction is to enzyme concentration. (2) lncreased activity of the enzyme without increase in its

concentration accelerates a biochemical reaction rapid response. e.g. peptides and protein hormones .

(3) Both effects. The response in this case is rapid and prolonged. How does activation of enzymes occur? (Fig.1)

lt occurs through the following series of steps: (1) For non - steroidal hormones (proteins, peptides and amino acids) : Hormones are carried by the blood stream to the cells of the effector organ. Hormones do not pass the cell membrane to the inside of the cells because of their large molecular size. Therefore, hormones bind to specific protein receptors on the outer surface of the cell membrane. This binding activates a protein enzyme on the inner surface of the cell membrane called adenyl cyclase. Adenyl cyclase catalyzes the conversion of

ATP cAMP + PPi cAMP inside the cells of the effector organ.

This cAMP diffuses through the cells of the effector organ acting as

a second messenger to stimulate the enzyme activity . N.B. The hormone is the primary messenger.

adenyl cyclase phosphodiesterase

ATP ------------------- ppi + cAMP ------------------------ 5 – AMP (AC) (PDE)

N.B.

lnhibitors of PDE (e.g. methyl xanthines cGMP, cIMP) cAMP potentiate hormonal effects.

Substances which potentiate the effect of PDE (e.g. ammonium ions

) cAMP and antagonize the hormonal effects.

Other second messengers include cGMP and prostaglandins (PGs). (2) For steroidal and thyroid hormones :

Hormones are carried by the blood stream to the cells of the effector organ.

Being lipid soluble, they enter the cell and bind to specific receptors inside the cytoplasm forming a complex.

The hormone-receptor complex moves towards the nucleus and enters through the nuclear membrane.

ln the nucleus, it accelerates RNA formation from DNA (transcription).

Newly formed RNA (mRNA) leaves the nucleus to the cytoplasmic ribosomes where the process of protein synthesis is stimulated according to the genetic code carried by mRNA (translation). Thus, the enzyme protein is increased.

N.B. Thyroid hormones bind directly to nuclear receptors.

(A) (B)

Mechanism of hormonal action of (A) protein hormones and (B) steroid hormones

Methods of Studying Endocrine Functions: 1) By measuring the concentration of a specific hormone in the plasma

using a highly sensitive method as radio immunoassay (RIA).

2) By observing the effects of injury or removal of part or all of the gland on body functions.

3) By observing the effects of injection of glandular extracts.

THE PITUTARY GLAND (HYPOPHYSIS)

Anatomically: - lt is a small gland present at the base of the brain, occupying the sella

turcica. - lt is 0.5 to 1 gm in weight; being slightly heavier in females. - lt is connected to the hypothalamus by the pituitary stalk (infundibulum)

Physiologically : The pituitary gland is formed of 2 parts, which differ both embryologically and functionally and are considered as 2 separate glands:

(1) The Anterior Pituitary (Adenohypophysis ): - lt develops from the roof of the buccal (Rathk's pouch ) and is of

epithelioid nature. - lt is formed of 3 parts:

1. Pars distalis. 2. Pars tuberalis. 3. Pars intermedia (intermediate part, or sometimes called

intermediate lobe.)

(2) The posterior pituitary (Neurohypophysis ): - lt develops from the floor of the 3rd ventricle. - lt is divided into :

1. The pituitary stalk (infundibulum); connecting the pituitary to the hypothalamus.

2. The nervous part (pars nervosa . N.B. There is no intermediate lobe in the human pituitary gland.

HORMONES OF THE PITUITARY GLAND (1) Anterior Lobe Or Anterior Pituitary Hormones :

1- Growth Hormone (GH, Somatotropin, STH). 2- Thyroid Stimulating Hormone (TSH, Thyrotropin). 3- Adrenocorticotrophic Hormone (ACTH, Corticotropin). 4- Follicle Stimulating Hormone (FSH). 5- Luteinizing Hormone or lnterstitial Cell Stimulating Hormone (LH,

ICSH) N.B. FSH and LH are referred to as gonadotrophic hormones (GnH).

6- Prolactin (PL), Lactogenic Hormone, Mammotropin, Luteoptrophic Hormone (LTH).

(2) lntermediate Lobe hormones :

- Melanocyte stimulating Hormone (MSH) . N.B. This hormone does not appear to have function in man .

(3) The Posterior Lobe Hormones : 1- Antidiuretic Hormone (ADH, or Vasopressin, AVP). 2- Oxytocin.

THE ANTERIOR PITUITARY GLAND

(ADENOHYPOPHYSIS)

Histologically: With the use of acid - base stains the anterior pituitary cells are

classified into 3 types: 1- Acidophil cells: Their cytoplasm is granular and the granules stain with acid dyes.

They from 35% of the total cells. They secrete protein hormones : growth hormone (GH) and prolactin

(PL) . 2- Basophil cells : Their cytoplasmic granules stain with basic dyes. They form 15 % of

the cells. They secrete :

- Polypeptide hormones (ACTH and MSH). - Glycoprotein hormones (FSH, LH and TSH). 3- Chromophobe cells : Their cytoplasm is non-granular. They form 50% of the cells. Their exact function is not fully determined .

N.B. Recent classification using immunocytochemistry and electron microscopy: 5 types of secretory cells were distinguished: 1. Somatotropes, which secrete growth hormone. 2. Lactotropes (also called mammotropes), which secrete prolactin. 3. Thyrotropes, which secrete TSH. 4. Gonadotropes, which secrete both LH and FSH. 5. Corticotropes, which secrete both ACTH and B-LPH.

Functions Of The Adenohypophysis: 1) lt stimulates growth of the body and skeleton. 2) lt stimulates growth and functions of target glands (thyroid, adrenal

cortex , testes and ovaries). Adenohypophyseal hormones are called therefore trophic hormones.

3) lt stimulates reproduction and sexual activities. 4) lt stimulates general and specific metabolism. Regulation Of Adenohypophyseal Function

The hormonal secretion by the anterior pituitary is regulated through 3 mechanisms : 1) The hypothalamic control. 2) Feed back control by the hormones of the effector organs (target glands). This is the long loop feed back . 3) Feed back control by the pituitary hormones themselves. This is the short loop feed back . 1- The Hypothalamic Control : The hypothalamus is a large nervous center that receives many afferent nerve fibers carrying information about the changes that occur outside or inside the body. According to information, the hypothalamus secretes hypothalamic factors (neurohormones) that reach the anterior pituitary (through the hypothalamic - hypophyseal portal circulation) to regulate its

secretion. Since the hypothalamus is the " mayestro " of the other endocrine glands, the function of these glands is regulated to face the original change and maintain homeostasis.

The hypothalamic- hypophyseal portal circulation:

The venous blood collected from the capillaries of the hypothalamus from venous channels that pass to the anterior pituitary where they pour their blood into a second set of capillaries and sinuses in-between the anterior pituitary cells. Significance:

i. The anterior pituitary receives its main blood supply from the venous blood collected from the hypothalamus.

ii. The hypothalamic neurohormones reach the anterior pituitary through this portal circulation to regulate its secretion.

The hypothalamic neurohormones (Releasing and lnhibitory Hormones): They are formed by special hypothalamic neurones that end in the

median eminence or tuber cinereum. They are secreted at their nerve terminal into the tissue fluid by

exocytosis. They are immediately carried by the capillaries of the portal

circulation to the anterior pituitary. Function: They control the secretion of the anterior pituitary

hormones. For each type of anterior pituitary hormone there is a corresponding

releasing hormone. Some anterior pituitary hormones have in addition a corresponding

inhibitory hormone i.e. (both releasing and an inhibitory hormone exist). Most anterior pituitary hormones are controlled predominantly by

releasing hormones, except in case of prolactin where the inhibitory hormone predominates.

2- Feed back control by the endocrine target organs (Long Loop Feed Back)

Feed back control means the effect of the target hormones on the secretion of both the hypoth. Neurohormones and pituitary trophic hormones i.e. either at a hypothalamic or pituitary levels.

lf this effect is inhibitory, the feed back is - ve.

lf this effect is stimulatory , the feed back is + ve. - Example:

Stress stimulates the hypothalamus Release of CRF Ant. Pit.

ACTH carried by blood to adrenal cortex Cortisol inhibit hypothalamic CRF

3- Feed back control by the pit . hormones themselves (Short Loop Feed Back )

portal circulation

Stimulus Hypothalamus Release of neurohormone ------------- Ant. Pit. To hypothalamus by blood or back diffusion

Ant.Pit. hormones ------------------------------------------------------------ inhibit the release of the corresponding releasing hormone.

Importance of the feed back control :

1. Maintain the normal level of the target gland hormone in blood. 2. Prevent over stimulation of the target gland by the corresponding

trophic hormone. 3. Adjust the rate of secretion of the target gland hormones according

to the body need.

Hypothalamohypophyseal connection and control of pituitary gland

GROWTH HORMONE ( GH, SOMATOTROPHIC HORMONE) - It is secreted by the acidophil cells of the ant. pit. (somatotropes). - lt is protein in nature (190 amino acids ) and shows species specificity. - lts rate of secretion is higher in younger than in older peoples and

shows daily variations. - The basal blood level is 3 ng / m1 .

Factors Affecting The Secretion Of Growth Hormone :

(A) Factors That Stimulate GH Secretion : 1. Hypoglycaemia. 2. Fasting and severe malnutrition. 3. Exercise. 4. Amino acid infusion specially arginine. 5. Neural stimuli e.g. emotional stress and onset of deep sleep.

6. Hormones as oestrogens, androgens, adrenaline ( adrenergic effect.) (B) Factors That Inhibit GH Secretion:

lncreased blood glucose level.

Corticosteroids.

Regulation of GH Secretion:

The hypothalamus controls GH secretion by means of 2 hormones: 1- Growth H releasing hormone GRH which stimulates the acidophil cells

of the ant. Pit. to secrete GH. 2- Growth H inhibitory hormone (GIH, Somatostatin) which inhibits GH

secretion. N.B. Somatostatin is also secreted by the delta cells of the pancreas and the duodenal mucosa. lt has an inhibitory role on the pancreatic hormones and gastric secretion. Functions of Growth Hormone: 1- Effect On Growth - GH Promotes growth of all tissues of the body that are capable of

growing through increase both size and No. of cells by mitosis. - GH stimulates growth of cartilage and bone indirectly. Mechanism:

GH stimulates the formation of small proteins called somatomedin from the liver, muscles and kidney. Somatomedin, in turn acts directly on cartilage and bone to promote their growth via the deposition of chondroitin sulphate and collagen. N.B. - There is no growth in length of bone after adulthood due to closure of

the epiphysis, and GH then causes only increase in thickness of long bones.

- Some physiologists believe that somatomedin is the growth H mediating factor which mediates most of the important functions of GH .

2- Metabolic Effects of GH :

A- On Protein Metabolism:

GH stimulates protein synthesis by:

lncreasing Am. Ac. uptake by the cells.

lncreasing formation of RNA in the nucleus (transcription).

Stimulation of the ribosomes.

Decreasing catabolism of proteins and Am. Ac. to provide energy.

B- On Fat Metabolism:

GH produces lipolysis i.e. Triglycerides free fatty acids F. Acids in blood.

GH enhances -oxidation of Fatty acids energy. Thus spares proteins and carbohydrates.

N.B. Excess GH Ketogenesis. C- On Carbohydrate Metabolism : GH causes:

glucose utilization by the cells.

Mechanism: Enhanced F.A. oxidation accumulation of acetyl Co. A

inhibits glycolysis.

lncreased glycogen deposition inside the cells due to accumulation of glucose inside the cells.

lncrease in blood glucose level (diabetogenic effect).

Mechanism: utilization of glucose by cells accumulation of

glucose inside the cells accumulation of glucose in the cells transport

of glucose across the cell membrane glucose accumulates in the blood. 3-Lactogenic Effect:

GH resembles prolactin in structure and thus it has some lactogenic effects.

DISORDERS OF GROWTH HORMONE SECRETION : 1) Increased Secretion of GH :

In these conditions there is loss of the mechanisms that regulate and control the secretion of GH. The acidophil cells continue to secrete GH in excess amounts. Cause: hyperplasia or acidophil cell adenoma. Effects: Depends on the age of occurrence;

I. lf it occurs before puberty i.e. (before closure of epiphysis) Gigantism.

II. lf it occurs after puberty i.e.(after closure of epiphysis) Acromegaly .

I. GIGANTISM:

lt occurs due to excess secretion of GH before puberty.

GH stimulates excess growth of all tissues of the body.

Effect on long bones :

1. There is a delay in the union of epiphysis increase in bone length so, the giant patient may reach 3 meters in height.

2. The growth in length of long bones is proportionate i.e.

The span = The height

The span is the distance between the distal ends of the laterally extended arms .

Effect on skeletal muscles : lncreased strength due to overgrowth at first, followed by marked weakness due to excess stretch by the growing long bones.

Effect on soft tissues: Overgrowth of the viscera (splanchonmegaly).

Effect on the gonads: The gonads remain infantile. How? The acidophil adenoma presses on the other pit. cells causing their

atrophy. Atrophy of basophils Gonadotrophic Hs Failure of

development of the gonads remains infantile.

Hyperglycemia glucosuria. (Diabetes) N.B. This type of diabetes is insulin resistant, because its cause is excess GH and not insulin deficiency.

metabolic rate. II. ACROMEGALY:

It occurs due to excess production of GH after puberty. GH stimulates growth of all tissues of the body except growth in

length of long bones. Effect the skeleton:

1) lncreased thickness of all bones: The skull:

i) The mandible is thickened and protruded (prognathism), with widely separated teeth.

ii) The nose is enlarged. iii) The supraorbital ridges and frontal

bosses are prominent. The vertebral column:

Thickening and enlargement of the vertebrae kyphosis. The hands and feet :

They become larger, broad with thick fingers and palms . - - - - - - - - - - - - - - - - - -- - Effect on soft tissues :

1. splanchnomegaly. 2. SK . muscle overgrowth. 3. Overgrowth of the skin, especially of the scalp and face

it becomes wrinkled

(Bulldog scalp). Effect on the gonads :

ln the early condition, there is hyperfunction of the sex organs. Later, these functions are depressed.

Hyperglycemia and increased metabolic rate. 2) Reduced Secretion of GH : (A) HYPOPITUITARY DWARFISM:

lt is due to arrested skeletal growth as a result of deficiency of GH or lack of the normal tissue response to GH, occurring before puberty. Causes : 1) Destructive lesions of the pituitary gland. 2) The secretion of inactive GH. The children have normal or even

increased blood GH level but it is ineffective. These children can respond to exogenous human GH.

3) Lack of target organ response to endogenous GH. 4) Laron dwarfism : GH release is normal, but there is a hereditary

deficiency of somatomedin. Features: The height is not more than 1 to 1.2 meters. The retardation of growth is symmetrical (proportionate) i.e.

The span = The height

Growth of all soft tissues is arrested. Mental development occurs normally, but the patient is emotionally unstable.

The gonads often show hypofunction infantilism (failure of sexual development).

(B) PITUITARY INFANTLLISM :

Pituitary infantilism refers to the condition of dwarfism combined with hypoganadism. The cause is deficiency of both GH and gonadotrophic Hs occurring since birth.

P A N H Y P O P I T U I T A R I S M: It is called also Simmond 's Disease or pituitary Cachexia.

- Cause: Atrophy of the ant. lobe of the pituitary deficiency of the trophic

hormones severe depression of the activity of the thyroid, adrenal cortex and gonads. This is due to one of the following:

1. Chromophobe adenoma pressure atrophy on other cells.

2. Craniopharyngioma.

3. Shehan's syndrome: postpartum haemorrhage

thrombosis of the pit. blood vessels pituitary necrosis. - The manifestations are due to decreased secretion of the pituitary trophic hormones:-

Decreased growth H causes: A. Loss in body weight (pituitary cachexia). B. Asthenia and easy fatigability.

C. Premature senility in the form of: - The patient looks older than his actual age. - Premature graying of hairs. - Decay and falling of teeth. - Dry wrinkled skin. - Easy fatigability.

Decreased activity of the thyroid:

Decreased tolerance to cold due to B.M.R. Decreased activity of the gonads

Atrophy of the accessory sex organs and decline in sexual activity:

- ln females: Amenorrhoea, genital atrophy, atrophy of the breasts and loss of axillary and pubic hair.

- ln males: Failure of spermatogenesis, loss of sexual desire and impotence .

Decreased activity of the adrenal cortex:

Hypoglycaemia and excretion of 17- ketosteroids in urine.

P R O L A C T I N lt is secreted by the acidophil cells of the adenohypophysis. lt is protein in nature. Functions:

Prolactin stimulates mainly the synthesis of milk and its constituents including fat, casein and lactose by the mammary gland which becomes ready for subsequent secretion. The mammary gland must be prepared (primed) for the action of prolactin by the ovarian hormones (oestrogen and progesterone). Regulation of Prolactin Secretion:

Normally, prolactin secretion is continually inhibited by the hypothalamic neurohrmone (prolactin inhibitory hormone; PIH). PIH proved to be dopamine. Prolactin, when released exerts a short loop feedback on the

hypothalamus to PIF and consequently inhibits its own secretion. Factors Which lncrease Prolactin Secretion:

1. Stress and exercise. 2. After the onset of deep sleep and persists during sleep. 3. Oestrogens.

4. lncreases during pregnancy to a maximum at delivery lt

decreases immediately after delivery for 8 days lt increase again by the suckling reflex.

5. All drugs which inhibit dopamine (PIH) increase prolactin e.g. chlorpromazine.

Factors Which Decrease Prolactin Secretion All drugs which stimulate dopamine synthesis or stimulate the

dopaminergic receptors e.g. L- Dopa, apomorphine and Bromocriptine.

MELANOCYTE STIMUKATING HORMONE - lt is formed by the basophil cells of the intermediate lobe in animals but

not in man. - lt has no physiological role in man.

- ln animals, it stimulates dispersion of melanin pigment granules in the

melanocytes of the skin darkening of the skin (essential for the process of camouflage). lt may also stimulate melanin production.

- ln man MSH resembles part of ACTH molecule and therefore conditions in which ACTH secretion is increased are accompanied by pigmentation of the skin.

THE POSTERIOR PITUITARY (NEUROHYPOPHYSIS)

The posterior pituitary is connected to the hypothalamus by the

pituitary stalk which contains the hypothalamo-hypophyseal tract. The tract is formed of the axons (nerve fibers) of the supraoptic and paraventricular nuclei of the hypothalamus. These fibers terminate in the posterior pituitary. Remember : A nucleus is a collection of nerve cells (cell bodies) in the C.N.S., having the same function.

The posterior pituitary secretes 2 peptide hormones : 1) Anti- diuretic hormone (ADH or vasopressin). 2) Oxytocin. Both ADH and oxytocin are formed by the neurones of the supraoptic

and paraventricular nuclei of the hypothalamus. N.B. The supraoptic forms mainly ADH, while the paraventricular forms mainly oxytocin.

The two hormones are then transported along the hypothalamo-hypophyseal tract to reach their nerve terminals in the posterior pituitary where they are stored in combination with a carrier protein; Neurophysin. The two hormones are released from their storage granules in the nerve terminals of the posterior pituitary according to nerve impulses descending from the hypothalamus along the hypothalamo-hypophyseal tract.

After producing their effects, ADH and oxytocin are rapidly inactivated through:

1) Metabolism in the liver via the 2 enzymes; vasopressinase and oxytocinase respectively.

2) Excretion by the kidney.

(1) ANTI- DIURETIC HORMONE (ADH OR VASOPRESSIN). FUNCTIONS OF ADH:

(1) On The Kidney: ADH increases water reabsorption from the cells of the distal

convoluted and collecting tubules of the kidney urine volume. How?

ADH (vasopressin) released Kidney ADH fix to receptors on

the kidney activate adenyl cyclase cAMP in these cells

activate protein kinase enzyme inside the cells phosphorylation of

proteins of cell wall widening of cell membrane pores reabsorption of water.

(2) On The Smooth Muscles of Blood Vessels: Physiological doses that are normally secreted and produce

antidureasis have no effect on smooth muscles of B.V.

Excess doses generalized vasoconstriction (hence its name

vasopressin) Blood pressure & myocardiac ischaemia due to coronary vasoconstriction.

(3) On other Smooth muscles:

ADH stimulates all smooth muscles colics.

ADH stimulates the smooth muscles of the uterus stimulate uterine contractions.

CONTROL OF ADH SECRETION :

ADH secretion depends upon the following factors: (1) Osmotic Pressure Of The Plasma The hypothalamus controls the O.P. of the plasma through the

osmoreceptors. These osmoreceptors are specialized neurones affected by changes in O.P. of plasma in the capillaries surrounding them.

Example: O.P. of plasma dehydration of neurones of osmoreceptors

sends impulses to stimulate the supra-optic nucleus of the hypothalamus send impulses along the hypothalamo-hypophyseal tract to nerve terminals in the

posterior pituitary ADH release retention of water by the kidney

O.P. of plasma to normal. O.P. of plasma has the opposite effect. (2) Changes in Volume of ECF and Blood: These changes act through stretch receptors (Volume receptors) to

regulate ADH secretion. Sites of volume receptors:

ln the wall of the atria and big veins. ln the wall of the carotid sinus and aortic arch.

Mechanism of regulation :

1. Minor in blood volume not sufficient to cause in blood pressure (B.P.) stimulates only the atrial volume receptors.

2. Marked in blood volume ( HAEMORRHAGE) sufficient to cause in

B.P. will stimulate both atrial and arterial receptors.

3. The receptors when stimulated afferent impulses to the ADH

release water reabsorption by the kidney the blood volume.

4. in plasma volume has the opposite effect. N.B. Haemorrhage is one of the most powerful stimuli of ADH release. The same mechanism for ADH release also releases

ALDOSTERONE from the adrenal cortex and both hormones act

together to the plasma volume. (3) Nervous Factors :

Stressful stimuli ADH

Exposure to cold ADH (4) Some Drugs :

Morphine, Nicotine and acetylcholine ADH.

Ethyl alcohol ADH (Alcoholics excrete more urine). ABNORMALITIES OF ADH RELEASE:

A) DIABETES INSIPIDUS: - It is due to a lesion in the hypothalamus destroying the regions of the

supraoptic and paraventricular nuclei ADH secretion. N.B. A lesion destroying the pit. stalk and the H-H tract cause only temporary diabetes insipidus because the hormone continues to be synthesized and released by the proximal healthy ends of the cut neurones. Manifestations: 1. Due to deceased ADH, urine volume is markedly increased

(polyuria). lt may reach 20 liters / day in severe cases. 2. The specific gravity of urine is very low and fixed ate 1002 - 1004.

3. Loss of large volume of urine excessive thirst and intake of water (polydypsia).

4. Loss of water soluble vitamins in urine. 5. Marked increase in basal metabolic rate.

B) NEPHROGENIC DIABERES INSIPIDUS

A condition in which ADH is secreted at the normal rate but the response of the cell wall of the kidney tubular cells is impaired due to receptor

defect the same manifestations. N.B.Diabetes insipidus responds to exogenous ADH administration but nephrogenic diabetes insipidus does not.

(2) 0 X Y T O C I N Functions of Oxytocin :

1) Milk ejection:

- lt is the most important function oxytocin. - Oxytocin stimulates the myoepithelial cells around the mammary

acini to contract and squeeze the alveoli and fine ducts, thus ejecting milk.

2) lt stimulates contraction of the uterine smooth muscles. Significance:

lt helps the process of normal labor. lt helps involution of the uterus after delivery. lt helps the ascent of spermatozoa in the female genital

tract. 3) Oxytocin has a slight pressor and antidiuretic effects. Control of Oxytocin Secretion:

Oxytocin is secreted in response to Neuroendocrine reflex. Afferent impulses reach the hypothalamus from different sites and stimulate the paraventricular nucleus to release oxytocin. Source of stimuli :

1) afferent impulses from the nipple during sucking initiate the suckling reflex. 2) afferent impulses during coitus, from the female genital tract.

Significance: Oxytocin released stimulates uterine contractions that help the

transport of seminal fluid in the female genital tract. 3) afferent impulses from the female genital tract during delivery.

Significance : Oxytocin stimulates uterine contractions and facilitates delivery.