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L#15 - Dr. Faisal Mohammed - Done by: marah madain The chemical structure of hormones or classes of hormones: Why are chemical structures important? For example, we have lipid-soluble hormones, because they are lipid-soluble they pass through the membrane which means that their receptors are located inside the cell, if these hormones are watersoluble they can’t pass through the membrane completely, so their receptors are located on the membrane and not inside the cell. Lipid-soluble hormones are not dissolved in the blood (because blood is aqueous), so these hormones need carriers to be transported, and these carriers are mainly proteins. -some problems occur due to the absence of a carrier for the hormone carrier, if there is no transporter the hormone will not work effectively (the hormone and the receptor are present but the transporter isn’t) What are the lipid-soluble hormones? Steroids: lipids derived from cholesterol Testosterone, Estradiol, Cortisol, Progesteron Thyroid: thyroxin, classified into either T3 or T4 T3 and T4: thyroid is a derivative of Tyrosine (amino acid), it is iodized, and when iodine binds to tyrosine we call it monoiodotyrosine (containing 1 iodine molecule), so T3 is tyrosine bound to 3 iodine atoms (monoiodotyrosin +diiodotyrosine) and T4 is tyrosine bound to 4 iodine atoms ( di+di) Nitric oxide (NO): a gas, and gases are lipid-soluble, the best example for lipid-soluble gases are O2 and CO2 (used in the respiratory system, they diffuse easily due to their lipophilic nature). Water-soluble hormones: Amines: derived from tyrosine & tryptophan (not all amines are lipid-soluble) Epinephrine and Norepinephrine: they are made up of tyrosine; tyrosine undergoes hydroxylation tyrosine hydroxylase tyrosine decarboxylase, this is for epinephrine, as for norepinephrine a methyl group is added. Polypeptides and proteins: we call a hormone a polypeptide when it is less than 100 amino acids (ADH or vasopressin), if the hormone is more than 100 amino acids we call it a protein( growth hormone, Prolactin) L#15 - Dr. Faisal Mohammed - Done by: marah madain Eicosanoids: special kind of hormones, they are derivatives of arachidonic acid (a fatty acid composed of 20 cardon atoms, 4 double bonds, exists in the membrane by the action of cyclooxygenaseprostaglandin or eicosanoids) Prostaglandin is responsible for pain sensation, as it synthesizes pain fibers in order for us to feel pain. -aspirin is a pain killer because it inhibits cyclooxygenase thus inhibiting the formation of prostaglandin. Glycoproteins: called glycoproteins because they are attached to 1 or more carbohydrate groups. FSH, LH, TSH and hCG Human chorionic gonadotropin (hCG): this hormone is used to diagnose the presence of pregnancy, it’s not found in non-pregnant ladies; because it’s secreted from the placenta. All glycoproteins are made of alpha and beta subunits, alpha is the same for all glycoproteins while beta is different, so when testing for pregnancy we test for beta-hCG. Hormones can also be classified as polar (hydrophilic), nonpolar (lipophilic). Pineal gland secretes melatonin: Has both water-soluble and lipid-soluble hormones. Prohormones and Prehormones: Hormones could be secreted as prohormones then the prohormone is broken down into hormones and other compartments. For example Proinsulin: made up of insulin and c-peptide, when it’s secreted it is broken down into insulin and c-peptide. It is very important to know if there’s a prohormone or not, for example: a patient that takes insulin and you want to test the insulin that is made by the body, you can’t test for insulin, so you test for c-peptide that is released by the breakdown of proinsulin , so when you measure the c-peptide you measure the endogenous insulin. Sometimes the hormone is secreted as a preprohormon, for example preproinsulin breaks down to proinsulin insulin. It is important for the hormone to be secreted as a prehormone sometimes, for example: T3 and T4, the thyroid secretes mainly T4 but the T3 hormone is four to five times more effective than T4, so T4 must be converted to T3 by the target tissue. -If hormones have similar chemical structure we know that they work in the same mechanism(not the same reaction), have similar location of receptors and similar events occurring in the target cell. L#15 - Dr. Faisal Mohammed - Done by: marah madain To respond to the hormones, target cells must have specific receptors: Hormones bind to the receptors according to their affinity (high kmlow affinity, low km high affinity) and saturation. The mechanism of hormone action: Responses depend on both hormone and target cell. -Lipid-soluble hormones bind to receptors inside the target cell. -Water-soluble hormones bind to receptors on the plasma membrane and activate second messenger system which results in amplification of original signal. Responsiveness of target cell depends on the hormone concentration, the abundance of receptors and the influence of other hormones (permissiveness, synergistic and antagonistic effects) -lipid-soluble proteins need carriers, when they reach the target cell they dissociate from the carrier and enter the cell, when they enter the cell they go to their receptor (in the slide they go to the nucleus), the hormone and the receptor are transported to the DNA and they bind to a specific area in the DNA called hormone responsive element (HRE), when they bind to this area they cause transcription of genessynthesis of protein (could be an enzyme or transporter, for example a glucose transporter that increases the entry of glucose to the cell, lowering glucose levels in the plasma), this process is slow, cAMP is a little faster nut binding of the hormone directly which may cause channels to open is a lot faster. Mechanisms of Steroid Hormone Action Cytoplasmic receptor binds to steroid hormone. Translocates to nucleus. DNA-binding domain binds to specific HRE of the DNA. Dimerization occurs. Process of 2 receptor units coming together at the 2 half-sites. Stimulates transcription of particular genes.