Endocrine System

The endocrine system is a system of glands that involve the release of extracellular signaling molecules called hormones. Glands are of two types: Exocrine: which release their cellular secretions through a duct which empties into a lumen of an organ. Endocrine: which have no duct and release their secretions directly into the blood. The main endocrine glands are the pituitary, thyroid, parathyroid, adrenal, pancreas and gonads.

HYPOTHALAMIC & PITUITARY HORMONES

The control of metabolism, growth, and reproduction is mediated by a combination of neural and endocrine systems located in the hypothalamus and pituitary gland. The pituitary is connected to the overlying hypothalamus by a stalk of neurosecretory fibers and blood vessels.

Pituitary gland
The pituitary gland is situated in sella turcica or hypophyseal fossa of the sphenoid bone attached to the brain by a stalk which is continuous with the hypothalamus. There is a communication between the hypothalamus and the pituitary gland by means of nerve fibers and a complex of blood vessels.

TSH

 Pituitary gland consists of three parts: 1) Anterior lobe (adenohypophysis), secretes various trophic hormones. 2) Posterior lobe (neurohypophysis), which is responsible for the secretion of oxytocin and antidiuretic hormone (vasopressin). 3) Middle lobe (pars intermedia), secretes melanocyte-stimulating hormone (MSH). Note: The posterior lobe hormones are synthesized in
the hypothalamus and transported to the posterior lobe.

Anterior pituitary hormones

Anterior lobe of pituitary is the master gland of the endocrine system as it produces peptide trophic hormones which affect the other endocrine glands. The anterior lobe secretes: 1. Growth hormone or somatotrophic hormone (GH & STH). 2. Thyroid stimulating hormone (TSH) or thyrotrophic hormone. 3. Adrenocorticotrophic hormone (ACTH). 4. Gonadotrophins (FSH and LH). 5. Lactogenic hormone or prolactin.

TSH

Links between Hypothalamic, Anterior Pituitary, and Target Organ Hormone.

Anterior Pituitary Hormone Growth hormone (GH, somatotropin) Thyroid-stimulating hormone (TSH) Adrenocorticotropin (ACTH) Follicle-stimulating hormone (FSH) Luteinizing hormone (LH) Prolactin (PRL)

Hypothalamic Hormone

Target Organ

Primary Target Organ Hormone or Mediator Insulin-like growth factor-1 (IGF-1) Thyroxine, triiodothyronine Glucocorticoids, mineralocorticoids, androgens Estrogen, progesterone, testosterone

Growth hormone-releasing hormone (GHRH) (+) Somatostatin () Thyrotropin-releasing hormone (TRH) (+) Corticotropin-releasing hormone (CRH) (+) Gonadotropin-releasing hormone (GnRH) (+) Dopamine ()

Liver, muscle, bone, kidney, and others Thyroid Adrenal cortex

Gonads

Breast

1- Growth hormone (GH)

Human GH has a single straight chain polypeptide structure of 188 amino acids containing two intramolecular disulphide bridges. Its secretion is regulated by GHRF=GHRH (factor = hormone). GHRF levels in the hypothalamus are reduced by corticosteroids and increased by thyroxine. GH secretion is increased by: Hypoglycemia, fasting, physical exercise, amino acids, stress, sleep, thyroxine and ACTH.

 Actions: 1- It stimulates the multiplication of the cells of epiphyseal cartilage and thus increases the length of the cartilage bone. It stimulates the growth of muscles. 2- It also increases the secretion of milk during lactation. 3- It increases nucleic acid and protein synthesis. Transfer amino acid content of the plasma into the tissues and helps in the growth of tissue. 4- It causes mobilisation of peripheral fat depot to the liver. 5- Stimulates carbohydrate storage BUT administration of GH produces hyperglycemia and glucosuria. 6- It increases intestinal absorption of calcium as well as its secretion.

Abnormalities
Hyposecretion during childhood leads to dwarfism which is characterized by stunted growth of the skeleton with resultant dwarfism. Hyposecretion during adult life leads to Simmonds disease and is characterized by dry and wrinkled skin, grey hair, atrophy of the sexual organs and cessation of menstrual cycle in the female. Hypersecretion during childhood leads to gigantism and is characterized by excessive skeletal growth. Hypersecretion during adult life leads to acromegaly and is characterized by excessive growth of facial bones, hands become large and spade like, thickening of facial and hands skin.

 Human GH is produced by recombinant DNA technique. Preparations available are: Sometrem (PROTROPIN) and Somatropin (GENOTROPIN).
The main use of growth hormone is in the treatment of dwarfism. Side effects include allergic reaction, pain at the site of injection, hypothyroidism, glucose intolerance (diabetes) and water retention (hypertension).

Somatostatin
It is a peptide hormone inhibits the release of GH, TSH, prolactin, insulin and glucagon. Somatostatin is found in the hypothalamus, other parts of the CNS, pancreas, and other sites in the G.I.T. Because of its shorter duration of action and lack of specificity in inhibiting only GH secretion, its use in the treatment of acromegaly is limited. Another newer synthetic compound, octerotride is a longer acting analogue of somatostatin and is used in acromegaly.

2- Thyroid stimulating hormone (TSH)

This hormone controls the growth and activity of the thyroid gland. It influences the uptake of iodine, synthesis of thyroxine (T4) and triiodothyronine (T3) by the thyroid gland and their release into the blood stream.

3- Adrenocorticotrophic hormone (ACTH)

Secreted under the control of CRF=CRH (corticotropin releasing factor=hormone) from the hypothalamus.

ACTH controls the growth of adrenal cortex and the synthesis of corticosteroids and is essential to life. ACTH stimulates the cortex of adrenal gland to produce its hormones which are of three types: the glucocorticoids, mineralocorticoids and the sex hormones.

 The amount of ACTH secreted depends upon the concentration in the blood of the hormones from the adrenal cortex (feedback inhibition).
SO ACTH is available as lyophilized powder which on reconstitution gives 40 IU/ml solution and is used mainly for the diagnosis of pituitary adrenal axis disorders.

4- Gonadotrophic hormones (GTH=GnRH) or Gonadotrophins

The basophil cells secrete gonadotrophins which control the growth and activity of the gonads and indirectly other processes connected with it. There are two gonadotrophins: follicle stimulating hormone (FSH) and luteinising hormone (LH) or = interstitial cell stimulating hormone (ICSH). They are glycoprotein in nature.

 FSH 1- In females, the target organs are the ovaries where it increases the number and size (maturation, development and ripening) of Graafian follicles and prepare them for ovulation. During its development, the follicles secrete its own hormone, estrogen. 2- In males, it stimulates spermatogenesis. Under the influence of this hormone, seminiferous tubules produce spermatozoa.

 LH 1- In females, it is responsible for: (a) Complete development of the ovarian follicles to secretory stage and secretion of estrogen. (b) Promotion of the final maturation of ovarian follicles and the formation of corpus luteum which secretes progesterone. 2- In males, the same hormone under the name of ICSH stimulates the development of interstitial cells and ultimately the production of testicular androgen, testosterone.

 Gonadotrophins are used in the treatment of - amenorrhoea, - infertility, - cryptorchidism (absence of one or both testes). - hypogonadotrophic hypogonadism in males.

 There are two types of gonadotrophins available: 1) Obtained from urine of pregnant women, chorionic gonadotrophin as 1,00010,000 IU (powder form, can be used after reconstitution by parenteral route). 2) Obtained from urine of menopausal women, menotrophin (combination of FSH and LH). Adverse reactions include polycystic ovary, edema, pain in lower abdomen and allergic reactions.

Nafarelin acetate
It is potent analogue (200 times more potent) of GnRH. It is rapidly absorbed into the systemic circulation following intranasal delivery. It stimulates the release of LH and FSH. After 2 to 3 days of daily administration, the pituitary becomes refractory to further stimulation. Adverse effects include hot flushes, change in libido, vaginal dryness, headache, emotional lability, nasal mucosal irritation, migraine and bone loss

5- Prolactin or lactogenic hormone

It is a single chain peptide hormone, isolated in pure form. It stimulates the breast to secrete milk immediately after the delivery of baby. It also stimulates the proliferation of the glandular elements of the mammary glands during pregnancy and helps in complete development of breasts. Prolactin secretion is under the inhibitory control of hypothalamus through PRIH Prolactin inhibitory hormone which is a dopamine and acts on pituitary lactotrope D2 receptor.

PIH = DOPAMINE

 Bromocriptine (Bromoergocriptine) is a semisynthetic ergot alkaloid and dopamine receptor agonist. It acts on pituitary lactotrophic cells to inhibit the synthesis and release of prolactin by agonist action on dopaminergic receptors. Adverse effects are nausea, vomiting, postural hypotension, behavioral alterations, mental confusion, psychosis. It is used in hyperprolactinemia and for suppression of lactation and breast engorgement (due to expansion and pressure exerted by the synthesis and storage of breast milk).

Posterior pituitary hormones 1- Vasopressin (Antidiuretic hormone, ADH)

Vasopressin is released by the posterior pituitary in response to rising plasma tonicity or falling blood pressure. Vasopressin possesses antidiuretic and vasopressor properties. A deficiency of this hormone results in diabetes insipidus. Vasopressin activates two receptors, V1 receptors are found on vascular smooth muscle cells and mediate vasoconstriction and V2 receptors are found on renal tubule cells and reduce diuresis.

 Desmopressin is a long-acting synthetic analog of vasopressin with antidiuretic-to-pressor ratio 4000 times that of vasopressin and can be administered orally. They are treatments of choice for pituitary diabetes insipidus, polyuria, polydipsia, hypernatremia or nocturnal enuresis. Headache, nausea, abdominal cramps, agitation, and allergic reactions occur rarely. Therapy can result in hyponatremia and seizures. Vasopressin (but not desmopressin) can cause vasoconstriction and should be used cautiously in patients with coronary artery disease.

 A group of nonpeptide antagonists of vasopressin receptors is being investigated for use in patients with hyponatremia or acute heart failure which is often associated with elevated concentrations of vasopressin: Conivaptan has high affinity for both V1a and V2 receptors (V1a specific not V1b so no vasoconstriction). Tolvaptan has 30-fold higher affinity for V2 than for V1 receptors (no vasoconstriction because no V1a nor V1b).

2- Oxytocin
Oxytocin is an octapeptide. It promotes contraction of the uterine muscle. It also causes contraction of the myoepithelial cells of the lactating breast and squeezing milk into the large ducts behind the nipple. Oxytocin takes part in the onset of parturition, expulsion of the foetus and placenta. It also facilitates the transport of sperm in the female genital tract. Oxytocin is used in induction of labour, in postpartum haemorrhage, abortion and in breast engorgement.