1 HORMONESIn our body, various metabolic functions are carried out by hormones which act as chemical messengers. Their activities are considerably affected by antagonist and agonist resulting in biochemical reactions. Furthermore, numerous hormones having small molecules.1.1 MECHANISM:Hormone will react on receptors in our body where it considers fits’. A hormone can be contemplated of as a key, and its numerous target sites have particular shaped locks on the cell wall. It works only when it fits in cell wall.The hormones can arise a cataract of other signaling pathways in a cell resulting an instant effect or a retard effect involves (glucocorticoids binding to DNA elements in a cell to begin the production of certain proteins, which takes a time to produce).
Endocrine system is the synchronize system that grasp hormones and their effects at particular level. One way this is achieved is via feedback loops’. The release of hormones is also controlled by proteins and neuronal signals.Hormones ease the chemical control over biochemical and metabolic processes through the whole body.
Via the hormones, endocrine system exerts control over the chemical processes, is analytical to homeostasis. The endocrine system differs from the nervous system, which release neurotransmitters to control electric and electrochemical processes and to effect homeostasis for a shorter time. The endocrine system is also differ from the immune system, which enlist immunomodulators to control over the cellular processes and also effect the homeostasis over a longer-term time scale.  (Page#310)Community status and living situation of an individual greatly affect the secretion of hormones1.2 FUNCTIONS OF HORMONESHormones are involved in different functions some of them are listed below;i. Modulation of Energy Storageii. Modification to new environmentiii. Involved in facilitation of development and growthiv. Involved in mood changes in people v. Involved in Mood swings vi. Involved in physical alterationsvii. Involved in secretion of numerous fluidsviii. Function and maturation of reproductive system (page#1103)2 ENDOCRINE GLANDS AND ORGANSStructure of human body representing hormones and their receptors in below diagramCommon organs and glands of the endocrine system involve the following components: Pituitary gland ” It is present inside the brain. It remains hormone levels in check and organizes other hormones. It can conduct about a change in hormone construction almost in the system by releasing its own stimulating’ hormones. It is also attached to the nervous system near hypothalamus. Hormones liberate by the pituitary gland involve gonadotropins, growth hormone, thyroid stimulating hormone, adrenocorticotropic hormone, anti-diuretic hormone, oxytocin.  Thyroid gland ” Inhibits in the neck at the front of the windpipe. It liberates thyroid hormone (T4 and T3) which is necessary for metabolism in body and body homeostasis. It is managed by Thyroid Stimulating Hormone which is released by the pituitary gland through a feed-back loop.  Parathyroid gland ” There are generally four parathyroid glands in a body which are present near the thyroid gland. The parathyroid gland is involved in release of calcium, vitamin D and phosphate. Adrenal glands ” There are two types of adrenal glands which present on the top of each kidney. They make a numerous different hormones. The outside part of the gland i.e. adrenal cortex produces cortisol, sex hormones and aldosterone. The centre of the adrenal gland called adrenal medulla produces the hormone known as adrenaline. Adrenaline is an example of a hormone which is particularly under the control of the nervous system.  Pancreas ” It is an organ of digestion which is surrounded inside the abdomen. It secretes insulin, which balance the amount of sugar in the bloodstream. It also makes numerous other hormones like somatostatin and glucagon.  Ovaries ” They are present in the female pelvis. They balance female sex hormones like estrogen. Testes ” They are present in the male scrotal sack. They fabricate male sex hormones like testosterone.Some other known endocrine organs include: Adipose tissue (fat tissue) ” It is considered to be a metabolically dominant. It produces hormones such as leptin, which affect appetite. It is also a site of estrogen production. Insulin also acts on adipose tissue. Kidneys ” They produce erythropoietin which increases red blood cell production, produce rennin which is needed for blood pressure maintenance and produces the active form of Vitamin D. Gut ” Involve a huge number of hormones and are being investigated and being understood to affect appetite and metabolism. Contained glucagon-like peptide 1, somatostatin and ghrelin which potentiate appetite. 3 HORMONAL MEDICATIONS:‚§ Estrogen and progesterone pills are used as oral contraceptive pills, In emergency used as contraceptive pills or use is hormone replacement therapy in several hormonal disorders ‚§ Thyroxin or levothyroxin pills are used to treat hypothyroidism or an underactive thyroid gland. Levothyroxin is also used to treat cretinism in infants. Thyroxin is a drug of choice when hypothyroidism is due to thyroid deficiency (page#243)‚§ Gonadotropin hormones that regulate the secretions of sex hormones such as estrogen and progesterone are used to treat several disease conditions, eg: infertility and prostrate disorders.‚§ Steroids may be given in the form of pills to overcome various allergenic, inflammatory or autoimmune disorders. They may be used in the various forms eg: inhaled form in bronchial asthma or as nasal sprays in allergic rhinitis. Steroids are responsible for the activity of various metabolic reactions. Steroid injections may also be given in cases of emergency such as acute asthma attack or shock. In addition, anabolic steroids can increase muscle growth and are administered to treat certain muscular and other developmental disorders ‚§ Insulin hormone Pancreas secretes insulin. Disorder in Insulin production leads to the increase sugar level. Insulin injections are used to treat individuals with type 1Diabetes or women with gestational diabetes who are failed to respond to other treatment approaches. Insulin is sometimes used by individuals with type 2 diabetes in cases where the disease has progressed to advanced stages.The hormone glucagon is administered in cases of severe diabetic hypoglycemia in order to restore blood sugar levels.Hormonal preparations are the major drugs used in medicine. Many of the hormones are naturally secreted in microscopic amounts and the replacement of certain hormones are therefore often designed to be released in amounts similar to those that would occur naturally in the body 4 STEROIDAL HORMONES: Steroid hormones include the sex hormones which are estrogens, androgens and progestin, Adrenocorticoids (mineralocorticoids, glucocorticoids) and the biosynthetic precursors, Steroid receptors are highly specific macromolecules found in central regulatory organs (e.g., pituitary, hypothalamus), in various target tissues (e.g., uterus, vagina, prostate), and in lower concentrations in the brain, liver, kidney, ovary, and many other organs. Steroids bind at their respective target site organ, At the level of transcription of the genetic message steroid molecules exert their influence on protein synthesis directly. The steroid hormones are transported through blood stream towards its target organ in aprotein-bound form.Steroids have common steran skeleton, the rings of this skeleton are labeled A, B, C, and D. Allfour rings are in the chair conformation in naturally occurring steroids; additionally,rings B, C, and D are always trans with respect to each other, whereas rings A and B can be trans or cis to each other (Pages 312,313,314 )4.1 TESTOSTERONE:It is a hormone present in the humans and in other animals. Testosterone in men is process particularly by testicles. Ovaries of Women also make testosterone, however in much smaller amounts then men. Its production begins remarkably during puberty. Testosterone is most frequently linked with sex drive, and plays a common role in sperm production. It also affects muscle and bone mass, in the way men store fat in the body. Testosterone is also involved in red blood cell production. A man’s testosterone levels can also affect his behavior and mood.STRUCTURE:It is an androgen sex hormone. Testosterone is compounded by the testes, and must be decreased to dihydrotestosterone before it will bind to the receptor. Between highly active synthetic testosterone analogs, have about 100 times greater activity than testosterone as androgens. 17-Methyl testosterone is orally active1-For a substance to have activity must have andostan skeleton.2-Oxygen at C-3 and C-17 are not necessary for activity.3-Introduction of 3-Hydroxy group and 3-Keto group increase activity.4-Hydroxy group at C-17 have no anabolic activity.5-Introduction of double bond at C-1 enhance anabolic effect.6-Replacement of carbon atom at position 2 with oxygen gives oral anabolic effect. [11, 12]MEDICINAL USES:Uses of testosterone include: For Males with testicular dysfunction. To rise lean body mass and muscle strength. Act as Performance enhancer. (Pages 329,330)4.2 PROGESTERONE:It is involved in production of the uterus and maintenance of pregnancy. It is because of decreased uterine motility through the inhibition of immunological refusal of the foetus.In comparison to other steroid receptors, the progesterone receptor is less distributed in body. Confined mostly to the female genital tract, breast, CNS and pituitary. The PR is normally present in the nucleus of target cells. Analogous to Estrogen Receptor, The antiprogestins also bind to Progesterone Receptors, but the conformation accessed is different from agonist bound receptor thus opposite effects are produced by interaction1-Ring is responsible for activity. 2-Hydrophobic in nature.USES:Uses of progesterone include For prevention of miscarriage. In treatment of menstrual disorder. 4.3 ESTROGEN:These are hormones that are of huge importance for reproductive and sexual development, mostly in women. They are also known as female sex hormones. The term “estrogen” introduce to all of the chemically alike hormones in this group, those are estrone, estriol and estradiol. Estrogen levels increase until the middle of the menstrual cycle, remain at a fairly constantconcentration, and then decline if fertilization does not take place. During the menstrual cycle, estrogen produces a suitable environment for the fertilization, implantation, and nutrition of an early embryo1-Not productive orally due to rapid metabolism in liver but ethinyl group at C-17 make it effective.2-Easter derivation prolongs the activity of a compound. 3-Introduction of OH group at C-6 C-7 and C-11 reduces the estrogenic activity. USES:Uses of estrogen include: It is used as birth control pills. Useful in menopausal conditions. Estrogen taken after menopause reduce the danger of osteoporosis. Various studies terminated that estrogen is responsible for treating cancer. Used in Hormone replacement therapy.(pages 324,323)4.4 ALDOSTERONE:Aldosterone regulates the water and salt balance of body and hence it is called as a mineralcorticoid. It also has a small effect on the metabolism of fats, proteins and carbohydrates. It is a most vigorous mineral corticoid. Because of decrease oral bioavailability and difficulties in adjusting doses it is used clinically. A figure of topically active glucocorticoids has been developed today. (Page#290,293)Aldosterone is synthesized from corticosterone in our body, a steroid extract from cholesterol. Renin “angiotensin system is complicated in establishment of aldosterone. In response to differences in blood pressure and volume and plasma sodium and potassium level, rennin is extracted from the kidneys. On a protein circulating in the plasma called angiotensinogen rennin acts and changing this substance into angiotensin I. Angiotensin I is then changed into angiotensin II, which effect in production of aldosterone from the adrenal glands 1. Existence of double bond at 4,5 position is necessary for activity.2. 2-3-Keto group on ring A is necessary for glucocorticoid and minneralocorticoid activity.3. Existence of 11-Beta hydroxyl group on ring C is necessary for glucocorticoid activity but not for mineralocorticoid activity.4. Hydroxyl group at C-17 on ring D is found on all natural aldosterones as well as some synthetic aldosterones which is a requirement for minneralocorticoid activity but not for glucocorticoid activity.5. Florination at 9-alpha position on ring B enhances the minneralocorticoid and glucocorticoid activity (Page#1223,1224)4.5 CORTISOL:It is also called as “stress hormone” because to its linkage to the stress response. It is a steroid hormone and is constructed in the adrenal glands. Cortisol receptors are found in most cells of a body. Functions of cortisol receptors include blood sugar levels, help reduce inflammation, regulation in metabolism and assist with memory formulation. It regulates the water and salt balance and aids control blood pressure in a body. In women, cortisol also helps in developing fetus during pregnancy.Occasionally tumors on the pituitary or adrenal glands can lead to a syndrome called as Cushing syndrome, which is effected by raised level of cortisol in the blood.1. Substituents added to cortisol can differ the bioactivity.2. Ketone group at C-3 is necessary for activity.3. Unsaturation rise the potency. (Pages 333,334) 5 PROTENICIOUS HARMONES:Consist of following hormones:5.1 INSULINE: It is a small protein having a molecular weight of 5808 in humans. It composed of 51 amino acids exhibit in two chains i.e. A and B linked between disulfide bridges; both chains are clear from each other. Pancreatic beta cells produce insulin at a low rate and at a much higher stimulated amount in response to a diversity of stimuli, commonly glucose. Inhibitory signals are hormones including insulin itself and leptin. Almost 60% of the insulin blood is usually cleared by liver, which is liberated from the pancreas by site of its side as the terminal of portal vein blood flow, although kidney clears about 35″40% of the endogenous hormone. Insulin help in the depot of fat, glucose within exclusive target cells as well as metabolic functions and cell growth is also synchronizing by it.1-There must be a bulk group on urea, when nitrogen, methyl and ethyl are inactive.2-There is only one Para-substituent on sulphonyl aromatic ring.3-The relation between amide nitrogen and sulphonamide nitrogen is dominant. USES: Uses of insulin include : It create energy from glucose for body. It distribute energy to the body. It is also used to treat hyperglycemia.(page#743-756)5.2 Glucagon:It is a hormone which regulates glucose level in body. It is produce from alpha cells present in the pancreas which are associated to insulin-secreting beta cells. Glucagon is responsible for maintaining blood glucose level.1-Benzene ring should contain one substituent at Para position (methyl, amino, chloro, bromo) increases hypoglycemic activity.2-Group attached to terminal Nitrogen transmits lipophilicity.3-Activity is lost if N substituent contain 12 or more Carbon.USES:Uses of glucagon include: It increase Glycogenolysis It also increase Blood Glucose level5.3 OXYTOCINIt is a nonpeptide which contains of six amino acids establishes a ring closed by a disulfide bridge, while the ring itself forms an antiparallel pleated sheet. The tail portion of the peptide, collected of Pro-Leu-Gly-NH3, strictly held in folded configuration. It results in the shrinkage of some smooth muscles and plays a essential role in milk excretion. It also has uterotonic action, shrinking the muscles of the uterus, and it is used clinically to influence childbirth. Receptor of oxytocin is a G- protein-coupled receptor.SAR1-Cyclic 9 amino acid peptide.2-Half life of about 6 minutes.3-Renewal of the amide groups of Gln 4 and Asn 5 in oxytocin by tetrazole analogues of aspartic, glutamic and ±-aminoadipic acids decreased biological activities.4-Oxytocin analogues in which the glycine amide residue in position 9 was exchange by tetrazole analogues of glycine had decrease activities.5-Steric effects of the side chain are insignificant. (Page#329-334)USES:Uses of oxytocin includes Induces labour pain Results in production of milk in females Results in miscarriage of a child due to uterus shrinkage5.4 VASOPRESSIN:Anti-diuretic hormone also called as Vasopressin. It synchronize the circadian rhythm.Anti-diuretic hormone also helps in regulating the body’s internal temperature, the proper flow of urine from the kidneys and blood volume.It consists of two analogs: lysine-vasopressin and arginine-vasopressin in which arginine-vasopressin is restored by lysine-vasopressin. Having configuration resemblance with oxytocin, except that the terminal tail is topographically free and not held by the ring. The physical role of the anti-diuretic hormone is the ordinance of water reabsorption in the renal tubules. In increased doses, anti-diuretic hormone promote the shrinking of capillaries and arterioles and results in increase in blood pressure; accordingly the name of these hormones. Because of their very similar structures1-Cyclic 9 amino acid peptide2-Interchane of an amino acid with a little and less hydrophilic amino acid side chain for the 4-glutamine, increase anti diuretic activity2- Interchange of D for L-arginine in the 8-position USES:It is used to treat Diabetic insipidus Septic shock Heamophilia A