Hormones-thyroid,hypotalamus,insulin referat





Hormones












Abstract




Hormones can be classified chemically into three major groups:

1.Steroid Hormones

These are steroid in nature such as Adrenocorticosteroid Hormones,Androgens,Estrogens and Progesterone.

2.Aminoacid Derivatives

These are derived from aminoacid tyrosine e.g.,Epinephrine,Norepinephrine and thyroid Hormones.

3.Peptide/Protein Hormones

These are either large proteins as small as medium size Peptides e.g.Insulin,glcogen,Parathormone,Cacitonine,Pituitary Hormones. 





Keywords:hormones,thyroid,hypotalamus,insulin




Introduction



Hormones are substances produced by Endocrine cells,realised into and transported by the circulatory system to their target organs,where they exert their effects.

Paracrin function,in contrast to endocrine action,involves the release and action of substances on neighbouring cells.

Autocrin function involves the release of an effects that then acts upon the cell that released the substance.The latter,two functions,paracrine and autocrine,do not involve transport by the circulatory system.

Hormones are classified as lipid soluble and water soluble.The lipid soluble hormones include:steroid hormones,the thyroid hormones and 1,25-dihydroxycholecalciferal,the water soluble hormones include cathecol amines,small peptides,polypeptides,proteins and glycoproteins.



Thyroid Hormones




The principal hormones secreted by the follicular cells of thyroid are:


1.Tyroxine(T4)

2.Tri-iodo-thyronine(T3)

3.Reverse “T3”


Chemistry of Thyroid Hormones


The hormones T4,T3 and “reverse” T3 are iodinated aminoacid tyrosine.The iodine in in tyrosine accounts for 80% of the organically-bound iodine in thyroid venous blood.Small amounts of “reverse” tri-iodo-thyronine monoiodotyrosine(MIT) and other compound are also liberated.


Biosynthesis of Thyroid Hormones


Two raw materials(substances) required by thyroid gland to synthesise the thyroid hormones:

-Thyroglobulin

-Iodine


Thyroid hormones are synthesised by the iodination of tyrosine residues of a large protein called “thyroglobulin”,which is a dimmer glycoprotein with a molecular weight 660 000.The receptor tyrosine molecules contains 115 tyrosine residues.

Thyroid acinar cells have three functions:

1.they synthesise thyroglobulin and stores as colloid in follicles;

2.They collect and transport T2 for synthesis of the hormones in the colloid;

3.They remove T3 and T4 from thyroglobulin secreting the hormones into the circulation.

Thyroglobulin is translated by the polysomes on the granular endoplasmatic reticulum of thyroid cells.The glycosylation of the molecule starts in the smooth endoplasmatic reticulum with the incorporation monnose and the other sugars as N-acetylglucosamine,Gal,fructose and sialic acid.The glicoproteins formed as above one packaged into small vesicles.The vesicles them move towards the apical plasma membrane and fuse with it,releasing their contents into the colloid of the thyroid follicles.

The other substrat required for thyroid hormone synthesis is iodine.Vegetables and and fruits grown and obtained from sea-shore and also sea fish are rich in iodine.Vegetables and fruits in hilly regions lock iodine.

Ingested dietary iodine is converted to iodide and absorbed from the gut.Of a total 50 mg of iodide in the body about 10 to 15 mg are in thyroids.

The normal daily intake of iodide is 100 to 200mg . Minimum requirement of iodine is 25 mg . this iodide is absorbed mainly from small intestine and is transported in plasma in loose attachment to protein ; can alsa be absorbed from Lungs , other mucous membranes and skin. About 2/3 of the ingested in excreted by the kidneys , the remaining 1/3 is taken up by the thyroid gland for synthesis of thyroid hormones. Thyroid stimulating hormone of anterior pituitary gland stimulates iodine uptake by the thyroid gland.


Metabolism of thyroid hormones


Liver plays an important role in the regulation of concentration and biologocal activity of thyroid hormones in blood.

De-iodination of hormones occurs in liver.Iodine is excreted as inorganic iodide in the bile and the urine.Conjugation of iodothyronins with glucuronic acid takes places in liver resulting to “glucuronides” being excreted in bile.




Action of Thyroid Hormones


The target cells include hepatocytes,renal cells,cardiac cells,neurons,lymphocytes and pituitary somatotrophs.

The biological effects of thyroid hormones are :

-calorigenic effect :thyroid hormones considerably enhance O2 consuption and oxygen coefficient in many tissues except brain ,testes and spleen and increase the heat production and BMR of the organism .

-growth and differentiation effects : thyroide hormones act synergistically with growth hormone to promote N retention,protein synthesis positive N balance,body growth and tissue diferention,by and enhancing the transcription of genes for tissue proteins.

-effects on carbohidrate metabolism:thyroid hormones raise the blood sugar,reduce glucose tolerance and increase glucose utilisation.

-effects on lipid metabolism:thyroid hormones potentiate the lipolytic action of adrenaline by up-regulating the beta-adrenergic receptors on the adipocyte membrane.

-effects on protein metabolism:thyroid hormones produce protein anabolic effects in moderate doses,but inhibit protein synthesis and increase blood amino acid level and urinary NPN in large doses.

Hypothyroidism causes Cretinism in children and Myxoedema in adults.

Growth in children is retarded and the child is mentally defective.He has coarse scanty hair and thick yellowish scaly skin.Cretinism occurs in areas where goitre is prevalent.

In Myxoedema occurs the puffiness of the face and hands in adults,the retention of water and NACl in the body,body temperature and pulse rate are subnormal,body weight is increased due to deposition of fat and retention of water,mental faculties are retarded and blood cholesterol and lipid levers are increased.


Hashimoto’s desease:

Thyroglobulin escapes from the cells of the gland and excites the production of antibodies which produce reactions with thyroid.Fibroses of the thyroid tissue develop leading to complete loss of thyroid function.

Severe hyperthyroidism leads to toxic goiter in which the patient complains of nervousness,restlessness,tiredness,undue sweating,breathless on exertion,tachycardia and palpitations,the subject cannot tolerate warm climate but can tolerate severe cold climate.

Hyperthyroidism is characterised by:nervousness,weight loss,hyperphagia,heat intolerance,increased pulse pressure,a fine tremor of the outstretched fingers.




Hypothalamic hormones

Hypothalamus secrets several peptide hormones which regulate secretion of the anterior pituitary hormones. These hypophysiotropic hormones include:

-thyrotropine –releasing hormone;

-corticotropin –releasing hormone;

-gonadotropin;

-growth;

-somatostatin;

-prolactin release;

-vasoactive intestinal peptide.

They are synthesised by hypotalamic peptidergic neurones.

Growth hormone releasing is a peptide made of 44 aminoacids. Vasoactive intestinal peptide stimulates the lactotroph and corticotrophin cell of anterior pituitary to secrete respectively prolactin and corticotrophin.

Thyrotropin releasing hormone is a natural tripeptide. It stimulates the transcription of the thyrotrophyne gene in pituitary thyrotropin cells to increase the synthesis of thyrotropin.

Gonadotropin releasing hormone is a decapeptide stimulates the pituitary gonadotroph cell to increase syinthesis as well as secretion of both the pituitary gonadotropins,FSH and LH.

Somatostatin secreted from gastrointestinal mocouse and pancreas also ,inhibits the release of growth hormonefrom pituitary somatotrop cell by lowering the intracellular Ca2+concentration .

Dopamine ,relesed from some of the hypothalamic neurones, acts as a prolactin release-inhibiting hormone.

The posterior pituitary hormones are vasopresin or Arginin Vasopresin and Oxytocyn.Vasopressin is an antidiuretic hormone.It resorbs water from the kidneys by distal tubules and collecting ducts.

Contraction of smooth muscles is the primary function of oxytocyn.There are basically two effects:one on mammary glands called as galactobolic effect and other on uterus,called as uterine effect.

A tropin or tropic hormones is one wich influences the activities of other endocrine gland,principally those involved in stress and reproduction.These are carried by the blood to other (target) gland.

Prolactin ,TSH,FSH and LH,ACTH are the tropic hormones secreted by the pituitary gland.

The main function of prolactin is to stimulate mammary growth and secretion of milk.The TSH stimulates the synthesis of thyroid hormones at all stages such as iodine uptake,organification and coupling and it enhances the release of stored thyroid hormones.

The principal actions of ACTH are exerted on the adrenal cortex and extraadrenal tissue.ACTH also stimulates the synthesis and secretion of glucocorticoids;it is found to increase the transfer of cholesterol from plasma lipoproteins into the fasciculate cells.ACTH has direct effects on carbohydrate metabolism that incude:lowering of blood glucose and the increase in glucose tolerance.

The pituitary gonadotropins influence the function and maturation of the testes and ovary and are of two types:Follicle Stimulating Hormone(FSH) and Leutenizing Hormone(LH).

In females FSH promotes follicular growth,enhances the release of estrogen.In males it stimulates seminal tubule and testicular growth and plays an important role in maturation of spermatozoa.

LH in female stimulates secretion of estrogens.

Melanocyte Stimulating Hormones(MSH) darkens the skin and is involved in skin pigmentation by deposition of melanin by melanocytes.


Abnormalities of Pituitary Function


Hyperpituitarisme

-excess production of growth hormone

-gigantism:results from hyperactivity of the gland during childhood,long bones increase in length and the patient reaches an abnormal height.

-acromegaly:this is due to hyperactivity that begins after epiphyses has been completed and growth has closed.The pacient exhibits characteristic facial changes.Foot requires large size shoes,there is an enlargement of nose and anlargement of hands,feet and viscera as well thickening of the skin.

-excess production of ACTH.





Adrenal Medullar Hormones


The cell of adrenal medulla are large , ovoid and columnar in type and called as pheochromocytes . The cells are grouped in clumps around the blood vessels. The adrenal medulla is derived from the primitive cells of the neutral crest , wich migrate into the centre of the foetal adrenal cortex forming medulla.

Active principales of adrenal medulla are Catecholamines –Adrenaline (Epinephrine) and Noradrenaline (Norepinephrine) –proportions of these two vary from species to species.

In human –adrenal medulla contains 80% of epinephrine and 20% norepinephrine .




Clinical aspect



No clinical state directly attributable to a deficiency of the adrenal medulla is known. But tumour of the medulla chromaffin cells in adrenal medulla or elsewhere can produce symptoms which stimulate those of hyperactivity of adrenal medulla . The tumour is calls pheochromocytoma.

It is characterised by: abnormal rise in blood pressure ,the hypertension due to pheochromocytoma may be paroxysmal or sustained.

The feature of a paroxysm are:

-headache, severe palpitation, sweating, nausea and vomiting;

-increased depth and rate of breathing, anxiety weakness and substernal pain.

-on physical examination –patient looks anxious skin-in pale,cool and moist;

-pupils are dilated;

-heart rate-is usually increased , but in some patients there is bradycardia extra-systoles may occur;

-body temperature is raised.



Hormones of the  gonads




The gonads are bifunctional organs that produce germ cells and the sex hormones. These two function are closely approximated , for high local concentration of the sex hormones are required from germ cell development. The ovaries produce steroid hormones estrogen and progesterone ; the testes produce spermarozoa and testosterone .

As in adrenal , a number of steroids are produced but only a few are active as hormones . the production of these hormones is tightly regulated through a feed back loop that involves the pituitary and the hypothalamus.

The gonadal hormones act by a nuclear mechanism similar to that employed by the adrenal steroid hormones.

Estrogens are of great importance in the development of the secondary sex characters of female at the time of pubery.

Under special circumstances , estrogen administration has been shown to result in the production of cancer . some of the syntthetic carcinogens are chemically related to estrogen . there is clinical evidence in the female children of mothers who given an estrogen during pregnancy.

In women administration its administration has resulted in an increased incidence of breast cancer and beging hepatomas .

Progesterone is secreted by the corpus lutenum of the ovary, the adrenal cortex and the placenta.



Pancreatic Hormones


The pacreatic istles secrete at least four hormones:insulin,glucagon,somatostatin and pancreatic vein,which empties into the portal vein-a convenient arrangement,since the liver is the primary site of action of insulin and glucagon.

Langerhans identified the islets in the 1860s but did not understand their function-nor did Von Mering and Minkomski,who demonstrated in 1889 that pancreatectomy produced diabetes.

The link between the islets and diabetes was proved by Banting and Best in 1921.They succeeded to obtain a hypoglycemic factor from islets of Langerhans.This factor was termed insulin since the islet tissue had been recognised to be the source of the hormone.It was quickly learned that bovine and porcine islets contained insulin that was active in human.Starting from 1922,insulin was in widespread use for the treatment of diabetes and proved to be life saving.

Insulin was the:

-first protein proved to have hormonal action;

-first protein crystallised;

-first protein synthesised by chemical technique;

-first protein shown to be synthesised in vivo as a large precursor molecule;

-first protein prepared for commercial use by recombinant DNA technology.

In spite of this impressive list of “First”,less is known about the exact mechanism of insulin action at molecular level.


Concluding thoughts



Hormones are very important for the organism because of their methabolical role.



Bibliography



1.Wills E.D.: Biomedical Basis of Medicine , WRIGHT ,Bristol , 1985

2.Das D.:BIOCHEMISTRY Eighth Edition , Academic Publishers , Calcuta (India),1993

3.Rama Rao : Textbook of Biochemistry for Medical Students , Publishers Distributors Ltd. , New Delhi , Sixth edition , 1992











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