What is endocrinology?What is endocrinology?

Endocrinology =

Intercellular Chemical Communication

Endocrinology is about communication systems & information transfer.

What is the endocrine systems for?What is the endocrine systems for?

Endocrine Functions

• Maintain Internal Homeostasis

• Support Cell Growth

• Coordinate Development

• Coordinate Reproduction

• Facilitate Responses to External Stimuli

The Endocrine system

The glands producing hormones are called endocrine glands. Endocrine glands are ductless glands which drop their secretions into the circulatory system for transport to a target organ. In contrast, the other major type of gland, exocrine glands, are glands that are connected by ducts to their target organs.

What is hormone?

hormone - "excite": "A chemical secreted by cells in one part of the body that is transported in the bloodstream to other parts of the body, where it affects particular target cells." - example: hypothalamus, pituitary

1) Is a physiological regulator2) Effective in small amount.3) Formed by living cells.

Classification

Hormones can be classified by several properties Classification

Hormones can be classified by several properties

1. Classification by site of action.

Secretions can be categorized by the site of action relative to the site of secretion.

Autocrine secretion – substance released by cell that affects the secreting cell itself (e.g. norepinephrine is released by a neurosecretory cell in the adrenal medulla, and norepinephrine itself inhibits further release by that cell - this is also an example of direct negative feedback)

Paracrine secretion - substance released by cell that affects neighboring cells. Not released into bloodstream (e.g. histamine released at site of injury to constrict blood vessel walls and stop bleeding)

Endocrine secretion - substance released by cell into bloodstream that affects distant cells.(e.g. testosterone is secreted by Leydig cells in testis, makes hair grow on your back) Though hormones may also have autocrine or paracrine actions, we're mainly concerned with endocrine actions.Exocrine secretion - substance released by cell into a duct that leads to epithelial surface(onto skin or into gut). Action doesn’t depend on receptors in target tissue.(e.g. sweat, saliva, spider silk)

2. Classification by origin.

Is commonly used to classify secretions, based both on origin and site of actionNeurohormones - endocrine, source = nerveGlandular hormones - endocrine, source = glandLocal Hormones - paracrine (source may not be gland)Pheromones - exocrine

3. Classification by molecular structure.

Amines- small molecules derived from amino acids. The catecholamines are epinephrine and norepinephrine, secreted by the adrenal medulla. Lipid insoluble.

Prostaglandins - fatty acids. Lipid soluble.

Steroids - cyclic hydrocarbons derived from cholesterol such as gonadal and adrenal. Lipid soluble

Peptides and proteins - large, complex, structure can differ among species due to amino acid substitutions such as hypothalamic and pituitary hormones. Lipid insoluble.

Effects of hormones: mechanisms of hormone action on target tissue

What does a hormone do when it arrives somewhere via the blood?

1. First level controlling action: target/non-target.

Hormones have their effects only on target tissues. Cells in target tissue have receptors, molecules that bind specifically to that hormone. In non-target tissue, cells have no receptors and are not affected by the hormone no matter how much of it is present.

2. Second level controlling action: receptor density.Target cells vary in the number of receptors they hold. A cell with

many receptors is more strongly affected than one with few receptors, when exposed to the same amount of hormone.

Receptor density for a given tissue changes through time. Down-regulation is a decrease in receptor density. Up-regulation is an increase in receptor density.

3. Third level of control: cellular mechanisms of action.

Once they arrive at a target cell, peptide and steroid hormones have different mechanisms of action. The difference is based on fat-solubility, which determines whether or not the hormone can penetrate the target cell's plasma membrane (which is a lipid bilayer).

Peptides are not fat soluble, so they bind to receptors on the target cell's surface, and act via a 'second messenger' in the cell. Second messenger is cyclic adenosinemonophosphate. CAMP activates an enzyme (a protein kinase), which activates otherproteins that produce the final 'effect' once secreted from the cell. Peptides don't directly alter gene expression, so the effects are generally short-term.

Steroids are fat soluble, so they bind to receptors in the cytoplasm, either in the cytosol or directly in the nucleus. When the steroid binds to the receptor, it disinhibits a DNA binding site on the receptor. The steroid-receptor complex then moves into the nucleus and activates or suppresses specific genes. By altering gene expression, steroids produce long-lasting effects.

Mechanism of hormonal actions

Action of Steroid Hormones

Action of Peptide Hormones

Hormones are removed from the blood and tissues by 6 basic methods:1. Enzymatic catabolism in blood and extracellular fluids 2. Endocytosis of hormone-receptor complex by target cell with

subsequent intracellular enzymatic catabolism and return of "cleared" receptor to plasma membrane

3. Liver enzymatic degradation and/or excretion in bile 4. Liver resynthesis (example: aromatization of testosterone into

estrogen) 5. Kidney excretion into urine 6. Hormonal binding to target sites

Metabolic Clearance Rate (MCR)MCR = Rate of disappearance of hormone from the Plasma /

Concentration of hormone per 1 ml plasmaThe actions and presence of Hormones attenuated in a number of ways.

Once released an unbound hormone may circulate through the body and be chemically altered by the liver or reactions in the blood so as to be unbindable to its originally intended target cells.

For example, excess Testosterone may be altered by the liver into Estrogen by a chemical process called Aromatization.

Hormone transport.

A)Protein bound B) Free forms (active form)

Many hormones travel in blood stream bound to proteins which protect them from enzymatic breakdown in blood .

Disassociation from the protein occurs at the target organ and the free hormone attaches to the respective receptor either on the cell membrane or in the cell.

Action of hormones:

Hormones can be involved in many function in the human body:

1. Developmental effect.2. Cell growth and cancer3. Central nervous system effects4. Effect on metabolism5. Effect on cardiovascular and renal function6. Effect on mineral and water metabolism7. Effect on skeletal function8. Effect on reproductive function9. Effect on immunologic function

Hypothalamus

1. In close association with the pituitary gland, the hypothalamus is the principle central Regulator and integrator of the endocrine system.

2. Almost all secretion by the pituitary is controlled by either hormonal or nervous signals from the hypothalamus.

3. Secretion from the posterior pituitary is controlled by nerve signals originate from the hypothalamus and terminate in the posterior pituitary.

4. Secretion by the anterior pituitary is controlled by hormones known as hypothalamic releasing or inhibiting factors or hormones.

Hypothalamic Hormones Pituitary Hormones Affected

Somatotropin releasing factor Somatotropin

Somatotropin releasing factor inhibitor

Somatotropin

Corticotropin releasing factor (CRH)

Corticotropin

Thyrotropin-releasing-factor (TRH)

Thyrotropin(TSH)

Gonadotropin releasing hormone (GRH)

FSH and LH

Prolactin releasing factor (PRL) Prolactin

Prolactin release-inhibiting factor Prolactin

MSH releasing factor Melanocyte-stimulating hormone

Regulatory Factors

Location: at the base of the skull in the sphenoid bone called the "sella turcica". Connected by a stalk of neural tissue to the brain.

Pars Tuberalis

Pars distalis

Pars Intermedia

AnteriorLobe

Capsule

Remnants of Rathkes Pouch

Pars NervosaPosterior Lobe

Infandibularstalk

2. Major divisions of each region: A) Adenohypophysis. Major cellular portion is the pars distalis or anterior lobe. A small collar of cells around the stalk is called the pars tuberalis. The section attached to the neurohypophysis is called the pars intermedia, or intermediate lobe.

Neurohypophysis. Fibrous process attached to the adenohypophysis is called the infundibular process or posterior lobe, or pars nervosa. Stalk connecting pituitary to brain is called the infundibular stalk. Region of nervous tissue at the top of the stalk (floor of the third ventricle) is called median eminence

How are the cells organized to produce the different hormones? Based on staining characteristics at the light microscopic level, the cell are divided into 3 classes. Red or orange staining cells are called acidophils, blue or purple cells are basophils and cells with little stain are called chromophobes

ANTERIOR PITUITARY GLAND

1) Acidopils:

which are about 35% of the total adenohyposis. From the pars Distalis of the acidophilic cells

Most abundant produce growth hormone/somatotropin (GH). These cells are ovoid and very active during growth and development. GH stimulates growth of long bones (at epiphyseal plates); Another group is more abundant during pregnancy and lactation. These produce prolactin which helps in the production of milk and during lactation. Some acidophils produce both growth hormone and prolactin; they are called mammosomatotropes.

2) Basophils: or Beta cells, which are about 15% of the total adenohypophysis.

One type produces adrenocorticotropin (ACTH) and beta-endorphin. ACTH stimulates the adrenal cortex during the flight or fight response to stress.

The second type produces the gonadotropins. Luteinizing hormone (LH) stimulates ovulation and formation of the corpus luteum; or testosterone production by the Leydig cells. Follicle stimulating hormone (FSH) stimulates the growth and development of the follicle and the function of the Sertoli cells in the testes.

The third type of basophil produces thyroid stimulating hormone (TSH) which stimulates the thyroid gland to regulate basal metabolism in the body. Some basophils produce more than one of these hormones.

3) Chromophobes: These may be resting or reserve cells. Or they may have secreted all of their product. Probably not a separate cell type, but a poorly granulated version of either a basophil or an acidophil.

HORMONES OF THE ANTERIOR PITUITARY GLAND

 1: GROWTH HORMONE- GH- (Somatotropic Hormone) GH is protein in having a molecular weight of about 21,000-48,000. It contains a single chain of polypeptide with 188-191 amino acids. It is secreted by the acidophilic cells of pars distalis. ACTIONS OF GROWTH HORMONE GENERAL GROWTH OF THE BODY Growth hormone is responsible for the growth of almost all the tissues of the body which are capable of growing. It actually increases the size and the number of the growing cells by increasing the mitotic division. It causes the specific differentiation of certain types of the cells like the bone cells and muscle cells.

Actions of growth hormone

METABOLIC EFFECTS Protein Metabolism 

Growth hormone increases the amino acid transport through the cell membrane. Thus the concentration of amino acid increases in the cell which promotes protein synthesis.

GH Decreases the protein catabolism, thus decreases the breakdown of cellular protein. This helps in building up of the tissues.

Fat Metabolism Growth hormone causes the mobilization of fat from the adipose tissues to form fatty acid. Thus the concentration of fatty acid increases in the circulation. During the utilization of fatty acid for the production of energy, a lot of acetoacetic acid is formed by the liver, which is released into the body fluids later on by producing Ketosis.Fatty acid some times accumulates in the liver as well resulting Fatty Liver.

Carbohydrate Metabolism GH decreases the peripheral utilization of glucose by the cell for the production of energy. As a result glucose accumulates in the cell and later on is converted into glycogen. Thus the concentration of the glycogen rises in the cell. This high concentration of glycogen inhibits the further entry of glucose in the cell. As a result blood glucose level rises. This condition leads to pituitary diabetes.

A rise in blood glucose level, stimulates the beta cells of islet of the langerhans in the pancreas to secrete insulin. With the passage of time, secretion of insulin rises, due to continuous increase in the blood glucose level, which causes hyper stimulation of the beta cells of the islets of langerhan, results hyper secretion of insulin which thus burns the beta cells eventually by inhibiting the further secretion of the insulin. This situation leads to diabetes mellitus. This action is known as diabetogenic action of growth hormone.

Mineral Metabolism GH causes the retention of sodium and chloride in the body. It accelerates the absorption of calcium in the intestine. It also stimulates the proliferation of the thymic lymph.

ACTION ON BONES

Growth hormone has an indirect action on the growth and development of bones. It enters the liver after the release and stimulates the synthesis of two compounds namely:Insulin like growth Factor-I (IGF-I), also known as Somatomedin-CInsulin like growth Factor-II (IGF-II),

 As a result, it acts continuously on the bones. It is mainly responsible for the conversion of chondriocytes into osteogenic cells. As a result, the size and the length of the bones increases till the fusion of the epiphysis with the shaft. At this point, the action of somatomedin is over, but since the secretion of growth hormone continuously goes on through out the life, it is responsible for the thickness of the bones mainly the membranous bones like the bones of jaws and the skull by stimulating the activity of osteoblasts.

REGULATION OF THE SECRETION OF THE GROWTH HORMONE

Nervous FactorSecretion of growth hormone is under the influence of 2 releasing factors by the hypothalamus, namely:Growth hormone releasing hormone (GHRH)Growth hormone inhibitory hormone (GHIH) When the basal concentration of the growth hormone (300ngm%. in adults and 500ngm% in children)is altered in the blood, hypothalamus starts releasing these Releasing factors.An increase in the level of GH, stimulates the secretion of GHIH, where as a decrease in GH level, stimulates the release of GHRH, by the hypothalamus, which reaches the anterior pituitary gland via hypothalamo-hypophesial portal blood vessels. GHRH, increases the secretion of growth hormone by the anterior pituitary gland, where as GHIH, decreases the GH secretion by the anterior pituitary gland.  Physiological Factor

Physiological factors like insulin induced hypoglycemia (50% fall in blood sugar), fasting, starvation, exercise, stress (surgical, emotional), trauma, and gentling and handling stimulates the secretion of growth hormone. Oppositely, sleep, darkness, noise and hyper secretion of TSH and ACTH, decreases the secretion of growth hormone.

2: THYROID STIMULATING HORMONE (TSH)

TSH is a glycoprotein secreted by the basophilic cells of pars distalis. Molecular weight is about 25,000.

Thyroid stimulating hormone (TSH), produced in the anterior pituitary, is the physiologic regulator of thyroid hormone synthesis and secretion.

TSH is consisting of α and ß subunits Alpha chain contains 96 amino acids, where as beta chain contains 113 amino acids. The alpha chain is identical to that found in two other pituitary hormones, FSH and LHb. α-Subunit facilitates binding to receptor, Thus it is its beta chain that gives TSH its unique properties.

TSH stimulates most of the processes involved in thyroid hormone biosynthesis and secretion by the follicular cells.

ACTIONS OF TSH

 GROWTH OF THYROID GLAND

TSH after the release stimulates the activity of Adenyl Cyclase in the thyroid thus it increases the accumulation of cyclic AMP in the thyroid slices. As a result, it increases the number of thyroid cell which are cuboidal in shape. It then converts these cuboidal cells into columnar cells. It also causes the development of thyroid follicles as well as the size and the Secretory activity of these follicles.

TSH later on, increases the iodine pump in the cell, which in turn increases the trapping of the iodine in side the cell.TSH acts on the intra-follicular thyroglobin in the follicles and causes the coupling of the di-idotyronine to form thyroxine (T4).

ACTION ON EYE

TSH has a direct effect on the extra ocular retro bulbar structure of the eye. It causes the bulging of the eye ball (Exophthalamus).

 Hypophysectomy, decreases the size, weight and the vascularization of the thyroid gland. As a result inorganic iodine is not taken up by the blood. Therefore the formation of the mono, die, and tri-iodothyroxine is reduced, which leads to a decrease in BMR and heart rate. Injections of TSH, in hypophysectomized animals, restore the normal activity of the thyroid gland

The most important controller of TSH secretion is thyroid-releasing hormone. Thyroid-releasing hormone is secreted by hypothalamic neurons into hypothalamic-hypophyseal portal blood, finds its receptors on thyrotrophs in the anterior pituitary and stimulates secretion of TSH. Secretion of thyroid-releasing hormone, and hence, TSH, is inhibited by high blood levels of thyroid hormones in a classical negative feedback loop. where as low thyroxine level in the blood stimulates the secretion of TSH. If low thyroxin secretion persists for long time, it is associated with a high rise in TSH secretion leading to thyroid hyperplasia.

REGULATION OF THE SECRETION OF TSH

3: ADRENO CORTICO TROPIC HORMONE (ACTH)This hormone is polypeptide in nature, secreted by basophilic cells of the pars distalis of anterior pituitary. Molecular weight of ACTH is approximately 45,000. It consists of 39 amino acids. Arrangement of amino acids from 25-33 is differentin different species. ACTH is heat stable and can stand up to 100C0.

ACTH IS A PRODUCT OF THE PROOPIOMELANOCORTIN GENE

ACTH acts on the adrenal cortex to increase cortisol and androgenic steroid synthesis and secretion (minor effect on aldosterone).

ACTH acutely increases cholesterol side-chain cleavage to form pregnenolone by increasing cholesterol delivery to the mitochondria. This occurs by increasing cholesterol ester hydrolyase activity via PKA phosphorylation and increasing StAR activity.

ACTH chronically upregulates expression of steroidogenic enzymes and growth of adrenal cells.

ACTH EFFECTS ON THE ADRENAL CORTEX

ACTH stimulates the activity of Adenyl Cyclase in the adrenal homogenate, thus it increases the cyclic AMP contents in the adrenal slices. ACTH is thus responsible for the growth and development of Zona fasciculate and Zona reticularis of the adrenal cortex. ACTH thus controls the growth of adrenal cortex and the synthesis of cortical from the cortex. This hormone is therefore known as the most essential hormone for the life (Life Saving Hormone).

REGULATION OF THE SECRETION OF ACTH 

HYPOTHALAMUSElectrical stimulation of various parts of the hypothalamus releases the corticotrophin releasing factor (CRF), which regulates the secretion of ACTH through negative feed back mechanism.Stimulation of the median eminence also produces the similar effects by increasing the secretion of CRF. Lesions in the hypothalamus reduce the release of CTF, which in turn reduces the secretion of ACTH. 

NERVOUS STRUCTURES (Other than hypothalamus)Stimulation of the peripheral nervous system, spinal cord, mid brain (Peripheral aqueous region), and the limbic system (Amygloid nuclei) stimulates the ACTH secretion. 

BLOOD LEVELS OF STEROID HORMONES High levels of blood steroid hormones through negative feed back mechanism controls the secretion of ACTH.PHYSIOLOGICAL FACTORSFactors like stress stimulate the pituitary-adrenal axis which stimulates the secretion of ACTH.Non specific stress like cold, epinephrine, estrogen, trauma and psychic reactions also stimulates the hypothalamus to releases CRF, which in turn stimulates the secretion of ACTH by the anterior pituitary.

(-)

(-)

(+)

(+)

GLUOCORTICOIDS EXERT NEGATIVE FEEDBACK ON THE HYPOTHALAMUS AND ANTERIOR PITUITA

4: GONADOTROPIC HORMONE

It is glycoprotein in nature. Molecular weight is about 30,000. Amino acid sequencing is yet not determined fully. Gonadotropins are classified into two types1: Follicle Stimulating Hormone (FSH)2: Luteinizing Hormone (LH) •the same 89-amino acid alpha subunit found in FSH and LH. A beta chain of 115 amino acids, which gives them ther unique properties

ACTIONS OF FSH Stimulates ovarian follicle development in females and spermatogenesis in malesACTIONS OF LHLH in femalesIn sexually-mature females, LH •stimulates the follicle to secrete estrogen in the first half of the menstrual cycle •a surge of LH triggers the completion of meiosis I of the egg and its release (ovulation) in the middle of the cycle •stimulates the now-empty follicle to develop into the corpus luteum,which secretes progesterone during the latter half of the menstrual cycle.LH in malesLH acts on the interstitial cells (also known as Leydig cells) of the testes stimulating them to synthesize and secrete the male sex hormone, testosterone. LH in males is also known as interstitial cell stimulating hormone (ICSH).

REGULATION OF THE SECRETION OF THE GONADOTROPINS

Coordinated by hypothalmus

The hormone that regulates the release of hormone from the anterior pituitary is gonadotrophin hormone releasing hormone (GnRH).

GnRH acts on gonadotrophs to stimulate the release of FSH and LH.

Gonadotropins regulate testicular function. The targets for LH are the Leydig cells and the targets for FSH are the Sertoli cells. Recall from Histology that:

Leydig cells reside in the interstituim of the testes and produce testosteron

5: PROLACTIN OR LACTOGENIC HORMONE OR LEUTOTROPIN

Prolactin is a protein of 198 amino acids. During pregnancy it helps in the preparation of the breasts for future milk production. Prolactin is responsible for the lactation in postpartum women with the combine action of estrogen and progesterone.

 Prolactin secretion is •stimulated by TRH •repressed by estrogens and dopamine

Prolactin causes the proliferation of grandular elements of breast during the pregnancy, thus it is responsible for the development of the structural components of the breast. Prolactin combines with the LH and stimulates the secretion of progesterone from corpus luteum, but it suppresses the ovulation during pregnancy. Prolactin causes the proliferation of epithelium of the esophagus and participates in its development. 

NERVOUS FACTORSuckling of the nipples of the mother’s breast during the lactation, produces afferent impulses, which stimulates the Prolactin Releasing Factor from the hypothalamus, by inhibiting the release of Prolactin Inhibitory Factor. As a result, ejection of the milk occurs. During the entire period of pregnancy, ejection of the milk is inhibited due to release of Prolactin inhibitory factor by the hypothalamus. 

HORMONAL FACTOR 

Sex hormones and placental gonadotropin (HCG) inhibits the Prolactin secretion. For example, injections of estrogen and progesterone, inhibits lactation. Similarly, although the breasts are fully developed, yet lactation does not occur during the pregnancy. It starts after the labor, when the placenta is fully proliferated and the estrogen/progesterone level falls. 

Hyper secretion of Prolactin is observed in the conditions like galactorrhea and Forbs-Albright syndrome (Persistent lactation). These conditions are observed in pituitary tumors (Chromophobe-adenomas)

REGULATION OF THE SECRETION OF PROLACTIN

6: MELENEN STIMULATING HORMONE (MSH)This hormone is mainly secreted by Pars Intermedia. It is classified into 2-types i.e. Alpha-MSH and Beta-MSH. Alpha-MSH is a single chain of polypeptide of 13 amino acids. This chain is very much similar to ACTH chain.• ACTH is a 39 Amino Acid polypeptide which is structurally related to α-MSH and β-lipotropin. α-MSH is within the first 13 AA of ACTH.•β-MSH is derived from the cleavage of β-lipotropin.

All three hormones are derived from the same gene product1 12

Tyr-Val-Met-Gly-His-Phe-Arg-Trp-Asp-Arg-Phe-Gly γ-MSH (1-12)

1 18

Asp-Glu-Gly-Pro-Tyr-Lys-Met-Glu-His-Phe-Arg-Trp-Gly-Ser-Pro-Pro-Lys-Asp β-MSH (1-18)

1 13

Ser- Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2 α-MSH (1-13)

1 39

Ser- Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-Gly-Lys- ACTH (1-39)

Lys-Arg-Arg-Pro-Val-Lys-...........Phe39

ACTIONS OF MSH MSH stimulates the synthesis of Melanin to produce the darkness of skin. In amphibians (Frog), this melanin secretion is associated with pigmentation. 

In human, action of MSH is not fully known, but, in clinical conditions like Addison ’s disease and during the pregnancy, secretion of MSH rises, which combines with ACTH to produce skin pigmentation.  

Evidences for temporary skin darkness have also been observed due to intravenous administration of MSH as a result of synaptic potential. 

Secretion of MSH is regulated by the pituitary stalk. Stimulation of this part increases the size of pars Intermedia to secrete large quantities of MSH.

POSTERIOR PITUITARY GLAND (NEUROHYPOSIS) 

 Anatomically posterior pituitary gland includes pars nervosa, infundibular stem and median eminence, but physiologically posterior pituitary means pars nervosa. It is composed up of glial like cells called pituicytes. These cells do not secrete any hormone. These pituicytes are classified into 4 types namely:

Adenopituicytes, Micropituicytes, Fibropituicytes, Reticulopituicytes 

Hormones of the posterior pituitary gland are generally synthesized in the cell bodies of the supra optic and paraventricular nuclei of the hypothalamus and are transported along with the neurophysin (Protein) to the nerve endings in posterior pituitary gland, requiring several days to reach the gland by the process called Exocytosis.

Posterior pituitary is supplied by two types of the nerve supplies: 

Tubero-hypophyseal tract: arise from median eminence, pass along with posterior wall of the infundibular stalk and enters the gland. Supraoptico-hypophyseal tract: arise from supra optic and paraventricular nuclei of the hypothalamus, pass by the anterior wall of the stalk, enters the neurohypophysis and ends around the blood vessels and cells of the gland

Where are the cell bodies that belong to these axons? These cell bodies are in the paraventricular and supraoptic nuclei in the hypothalamus. Different cells produce oxytocin or vasopressin in each nucleus. Oxytocin and vasopressin are synthesized on the rough endoplasmic reticulum and packaged in granules by the Golgi complex. Then they are sent down the axon which travels to the median eminence. Some of the axons end there. Others go down to the posterior lobe and end on the capillaries in this region. Some endings are so large, they accumulate many storage granules. These endings are called Herring Bodies.

POSTERIOR PITUITARY GLAND (NEUROHYPOSIS)

HORMONES OF POSTERIOR PITUITARY GLAND

1: OXYTOSIN

 It is synthesized in paraventricular nuclei of the hypothalamus. It is an octapeptide, with the molecular weight of about 1000. Oxytocin is a peptide of 9 amino acids. It is a strong constrictory hormone. One unit of oxytocin causes strong contraction of the uterus.

ACTIONS OF OXYTOSIN Its principal actions are: •stimulating contractions of the uterus at the time of birth•stimulating release of milk when the baby begins to suckle

Action on UterusAction of oxytocin on virgin uterus is almost negligible, but during the later stages of the pregnancy, just before the birth, oxytocin is released in large quantities and takes part in the process of parturition, expulsion of the fetus and placenta. This effect persists for some time

Action on Breast

Oxytocin has a more prominent role after the labor to initiate lactation. The sucking stimuli on the nipples of the breast transmit sensory signals to the hypothalamus in paraventricular nuclei to stimulate the secretion of oxytocin. Oxytocin is then carried by the blood to the myo-epithelial cells of the breast that surrounds the alveoli of mammary gland. In less than a minute, after the beginning of suckling, milk begins to flow due to strong contractions in the myo-epithelium. This phenomenon is known as milk ejection.

REGULATION OF THE SECRETION OF OXYTOSIN

Control of release of oxytocin can be at all points in the circuitry, at the site of the cell body in the hypothalamus, at the median eminence, and at the site of the ending in the pars nervosa/posterior lobe. Control can be either via blood supplyor via direct nerve fiber communication up in the brain. Hypothalamus through supra optico hypophyseal tracts controls the secretion of oxytocin. Factors like suckling and labor stimulates the release of oxytocin. Hypophysectomy as well as the injections of progesterone decreases the release of oxytocin, where as estrogen has opposite effects.

2: ANTI-DIURETIC HORMONE (ADH-VASOPRESSIN)

ADH is secreted by the supra optic nuclei of the hypothalamus in relation to stress and dehydration. It is an octapeptide with the molecular weight of about 1100. ADH is a peptide of 9 amino acids.It has a vasopressive (Constrictory) effect on blood vessels.. It is also known as arginine vasopressin. ADH acts on the collecting ducts of the kidney to facilitate the reabsorption of water into the blood. This it acts to reduce the volume of urine formed (giving it its name of antidiuretic hormone).

ACTIONS OF ADH  

Blood vessels and blood pressure

 

ADH has a vasoconstrictory effect on peripheral blood vessels, thus it raises the peripheral blood pressure. ADH causes general vasoconstriction to all the blood capillaries thus by rising the blood pressure, followed by a sudden fall in blood pressure due to carotid depression.

 

Heart Rate

ADH produces coronary vasococtriction and a rise in arterial blood pressure which reflexly reduces the heart rate. 

Respiration

A high rise in blood pressure due to vasoconstriction, ADH intern stimulates the respiratory centers to produce hyperpnoea followed by apnea. 

Kidney

 ADH is a renal vasoconstrictor; it thus reduces the renal blood flow which decreases the glomerular filtration rate and a decreased formation of urine. ADH thus acts as an anti diuretic hormone.

Muscles

 ADH causes the contraction of intestinal and stomach muscles to initiate the gastrointestinal motility. 

Metabolism

 ADH causes the glycogenolysis. As a result hyperglycemia and glycosuria is observed. ADH reduces the sugar tolerance as well.

REGULATION OF SECRETION OF ADH 1: OSMOTIC REGULATION When large quantities of water are taken, plasma becomes diluted and the colloidal osmotic pressure falls. As a result, supraoptic nucleus of the hypothalamus immediately transmits an impulse to the posterior pituitary to reduce the secretion of ADH. Consequently, water absorption is reduced and large amount of diluted urine is passed. Thus excess water is lost from the body. 

Oppositely, when there is condition of dehydration or hydropenia or when large amount of hypertonic saline solution is injected, colloidal osmotic pressure rises which stimulates the release of ADH by stimulating the osmoreceptors present in the supra optic nucleus of hypothalamus. ADH thus by producing renal vasoconstriction reduces the formation of urine. As a result, very concentrated urine with fewer amounts is excreted out.

 2: PHYSIOLOGICAL REGULATION Hypoxia, pain, cholinergic stimulation, emotional and physical stress, electric stimuli, nicotine and morphine stimulates the secretion of ADH. Oppositely, alcoholism, depress the secretion of ADH thus by producing excess urination. 

Baroreceptors located at thyro-carotid junction stimulate the release of ADH. Hemorrhage (10%) also stimulates the release of ADH.

DISORDERS OF ANTERIOR PITUITARY GLANDIt is divided into two main type:1)Hyper secretion 2) Hypo secretionCauses of hyper secretion:• Increase stimulus of pituitary gland• Increase in the cell number which produce the hormone, which is mainly due to tumor.When the cell become large in size it known as hypertrophy, and when there are increase in

number of affected cells it known as hyperplasia.

The main cause of hypo secretion is Ischaemia due to:1) Thrombosis in blood vessel. 2) Decrease size of blood vessel and blood volume

DISORDERS OF CHROMOPHIL CELLS

HYPER-SECRETION OF ACIDOPHILIC CELLSThe increase in secretion is due to adenoma1:GIGANTISM (Pre-Puberty)Hyper-secretion of acidophilic cells (GH) before puberty produces gigantism and it

takeplace before completely growth of the bone. Symptoms include:1:Tall skeleton2:Rise in BMR, Hyperglycemia, Excessive sweating3:Enlargement of viscera and well developed muscles4:In later stages hypopituitrism and its degeneration

2:ACROMEGALY (Post-puberty)

 

Hyper-secretion of acidophilic cells (GH) after puberty produces Acromegaly.This take place when the bone is completely grow.

Symptoms include:

1:Over growth of the jaws and molar bones. Megale (enlargement) of the hands and feet and face. Rise in anterior-posterior chest. As a whole Guerrilla like appearence.

2:Thickening of the subcutaneous tissues of the hands, feet, nose, lips and skin.

3:Enlargement of the viscera (Heart, lungs, liver, kidney, pancreas, spleen)

4:Hyper-secretion of thyroid, adrenal, thymus and Prolactin.

5:Hyperglycemia, high BMR, hypertension, excessive sweating drowsiness and lethargy.

6:Hypertrophy of gonads followed by their atrophy.

7:Diminished libido and impotence in males and sterility, lactorrhea and amenorrhea in female.

8) In lab investigation there is increase in organic phosphate, glucose and there is hyper calciurea.

HYPO-SECRETION OF ACIDOPHILIC CELLS 1:DWARFISM (Pre-puberty)3-types of dwarfism are observed before puberty, as a result of decreased secretion of growth hormone by the acidophilic cells. These are:

a) LORAIN-Levi TypeHeight is less than 3-feet. Secondary sex characters and sex organs are poorly developed. Intelligence and metabolic activities are normal. GH receptor has various point mutations which can associated with short stature in children. Non-Functional GHRs due to mutations cause Laron Dwarfism; normal GH expression but non-functional receptor.

b) BRISSAUD TYPE Short height, Chubby and round face. No beard and mustaches.Excessive deposition of fat on the body (FATTY BOY OF DICKENS). c) MIXED TYPEShort skeleton, Fatty and hairless body, thick nasal sinuses. 2:ACROMICRIA (Post-puberty) Bones of the face, hands and feet are small. Loss of body hairs, depressed secondary sex characters and hypogonadism.

HYPER-SECRETION OF BASOPHILIC CELLS 

CUSHING’S DISEASE Chronic glucocorticoid excess leads to the physical features known as Cushing’s syndrome. It is caused by abnormalities of the pituitary or adrenal or as a consequence of ACTH secretion by nonpituitary tumors (ectopic ACTHsyndrome). Cushing’s disease is defined as the specific type of Cushing’s syndrome due to excessive pituitary ACTH secretion from pituitary tumor. Cushing’s disease is much more common in women than in man.

Clinical features

1:Obesity: Obesity is the most common manifestation and it is classically central affecting mainly the face, neck , trunk. Accumulation of fat in the face leads to the typical (MOON-FACE) which is present in 75% of cases. in both the sexes

2.Skin changes: Atrophy of the epidermis and its underlying connective tissue leads to thinning (a transparent appearance of the skin. Pigmentation over the abdomen and thighs due to loss of protein matrix. Women are affected 4-times more than the males.

3:Thirst and polyuria: It is secondary to hyperglycemia and diabetes mellitus occur in about 10% of patients. Glycosuria, Eosinopenia and lymphocytopenia in both the sexes.4. Gonadal dysfunction: A very common features as a result of elevated androgens (in female) and cortisol mainly in male. Amenorrhea occurs in 75% of premenopausal women and usually accompanied by infertility. Decreased libido is frequent in males.

5.Excessive hair growth (Hersutism), is present in about 80% of female patients due to hypersecretion of adrenal androgens.

6. Psychologic disturbances:

Muscularization (appearence of beard and mustaches Amenorrhea, Virilization (Depressed libido)

 

DISORDER OF POSTERIOR PITUITARY GLAND

DIABETES INSIPIDUS

Large quantities of urine (about 24 liters/day) with low specificgravity (1.002—1.006) is excreted out with low chloride ion associated with intense thirst. Most commonly observed due to tumors of the supra optic nucleus of the hypothalamus and the lesions in supra optico hypophyseal tract. Also it is caused by a deficiency in Vasopressin or by an inability of the nephrons to respond to vasopressin. In Nephrogenic Diabetes Insipidus, the collecting ducts fail to increase their water permeability in response to vasopressin.

a.In humans Diabetes insipidus is associated with gene defects associated with the gene sequence encoding VP-associated neurophysin.b. Urinates a very dilute urinec. Drinks constantlyADH injections restore diabetes insipidus