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abdi Hrmone.pptx

  2. Objectives •At the end of this chapter the students will able to: –Identify some of the major Adrenal hormone –List and explain the hormones of adrenal hormones along with their abnormalities –Understanding the mechanism action of adrenal steroid hormones
  3. Adrenal glands Adrenal glands: two small, triangular-shaped glands located at the upper portion of each kidney It is composed of an outer cortex and an inner medulla Outer cortex ◦ Outermost zona glomerulosa: Synthesis site of mineralocorticoids ◦ Central zona fasciculata: Synthesis site of glucocorticoids ◦ Inner zona reticularis: Synthesis site of adrenal sex steroid hormones Inner medulla: Synthesis site of catecholamines.
  4. Adrenal cortical steroid synthesis The adrenal cortical steroid hormones are derived from the cholesterol via a branched metabolic pathway
  5. 1.Glucocorticoid (Cortisol) Cortisol is the principal glucocorticoids. Target organ - every cell of the body Effects ◦ Regulation of carbohydrate, protein and lipid metabolism; maintenance of blood pressure and suppression of the immune response General characteristics ◦ Steroids, lipid-soluble, protein bound, slow effects
  6. Regulation of cortisol secretion Hypothalamic regulation: it produces cortico-tropin releasing factor(CRF). Pituitary regulation: it produces ACTH in response to CRF Negative feed-back: cortisol has direct –ve feed back effect on hypothalamus to decrease CRF & on pituitary to decrease secretion of ACTH. Effect of physiological stress on ACTH secretion: Physical & mental stress can lead to increase cortisol secretion within minutes via increase ACTH.
  7. Glucocorticoid transport The lipid-soluble glucocorticoids are transported in circulation bound to carrier proteins ◦ Cortisol is 90-97% protein-bound ◦ Cortisol-binding globulin (CBG) – major transport protein ◦ Albumin ◦ Sex-hormone binding globulin (SHBG) ◦ Conditions that change the level of binding protein affect the level of total hormone, but not of the biologically active free hormone ◦ Causes of increased CBG ◦ Estrogen, hyperthyroidism, etc. ◦ Causes of decreased CBG ◦ Malnutrition, chronic liver disease, etc.
  8. Hypersecretion of cortisol Cushing’s syndrome ◦ Clinical disorder that result from supraphysiological level of cortisol in the circulation (hypercorticortisolism) ◦ The cause can be primary to the adrenal cortex (adrenal adenoma in carcinoma) secondary to overproduction of ACTH (pituitary adenoma) or an ectopic carcinoma that produce ACTH, eg carcinoma of the lung. ◦ The diagnosis is confirmed by dexamethasone suppression test. ◦ Plasma ACTH levels are low in primary adrenal disease and high when there is uncontrolled production of ACTH by a neoplasm.
  9. Hyposecretion of cortisol Adreno cortical insufficiency, evident by a low plasma cortisol concentration The causes may be: ◦ Primary to the adrenal cortex because of destruction of cortical tissue by autoimmundisease or infection (addison’s disease) or ◦ Secondary to ACTH deficiency The diagnosis is confirmed by finding a subnormal cortisol response to the administration of exogenous ACTH (rapid ACTH stimulation test)
  10. Serum cortisol measurement Adrenocortical hormone tests are typically performed on blood plasma or 24-hour urine samples. Reference ranges for blood serum cortisol levels: Adults (8 A.M.): 6-28 μg/dL; adults (4 P.M.): 2-12 μg/dL. Child 1-6 years (8 A.M.): 3-21 μg/dL; child 1-6 years (4 P.M.): 3-10 μg/dL. Reference ranges for urine (free cortisol): Adult: 10-100 micrograms/24 hr. Adolescent: 5-55 μg/24 hr. Child: 2-27 μg/24 hr.
  11. 2.Mineralocorticoids (aldosterone) Aldosterone: the principal mineralocorticoid hormone . Target organs - kidneys, sweat and salivary glands and GI tract. Effects: Aldosterone regulates electrolyte balance and extracellular fluid balance . ◦ It regulates blood volume and blood pressure. ◦ In the kidney, aldosterone causes active sodium reabsorption, potassium and hydrogen excretion and passive water reabsorption.
  12. Aldosterone release Three release stimulators ◦ Renin-angiotensin system (RAS) – primary stimulation ◦ Extracellular potassium and sodium ◦ ACTH Aldosterone Its production is primarily controlled by the renin-angiotensin system. ACTH has a slight stimulatory effect on aldosterone synthesis, but this is usually of no significance.
  13. (Aldosterone ) Con.. Renin  Protein produced by the juxtaglomerular apparatus of the kidney in response to decreased renal pressure and/or decreased serum sodium levels.  Acts on angiotensinogen to produce angiotensin I which is converted to angiotensin II by angiotensin converting enzyme.  Angiotensin II is a potent vasoconstrictor and also stimulates secretion of aldosterone by adrenal cortex.
  14. Aldosterone control Atrial natriuretic peptide Plasma k+ level Role of ACTH Plasma Na+ level Renin- angiotensin system Aldosterone has negative feedback on the juxtaglomerular apparatus of the kidney.
  15. Hyperaldosteronism Primary hyperaldosteronism (conn’s syndrome) ◦ It is overproduction of aldosterone due to the presence of an aldosterone secreting adrenal adenoma. ◦ These patients usually have elevated serum Na+ concentration, lowered K+ and hypertension. Secondary hyperaldosteronism ◦ It result from abnormalliteis in the renin-angiotensin system ◦ It result from ◦ Excess production of renin→associated with increased plasma renin
  16. Hypoaldosteronism Aldosterone deficiency is most often due to destruction of the adrenal glands. If sodium intake is not adequate, the patient will develop severe water and electrolyte abnormalities and may die from vascular collapse and/or hyperkalemia.
  17. Laboratory diagnosis Determination of aldosterone by RIA and FPIA Determination of sodium and potasium in serum and urine Two blood samples are often drawn for aldosterone evaluation, one in the early morning and one mid-afternoon. Because a 24-hour urine specimen reflects hormone production over an entire day, it will usually provide a more reliable aldosterone measurement. Elevated blood levels should ideally be confirmed with a 24-hour urine test.
  18. Cont… Results will also vary between patients depending upon average sodium intake, time of day, source of specimen, age, sex, and posture. Reference ranges for blood plasma levels: radioimmunoassay ◦ Supine: 3-10 ng/dL. ◦ Upright: Female: 5-30 ng/dL; Male: 6-22 ng/dL ◦ Urine: 2-80 micrograms/24 hr.
  19. 3.Catecholamines Catecholamines – epinephrine, norepinephrine and dopamine. ◦ Epinephrine is the major adrenal catecholamine (80-90%) ◦ Affects metabolism (mobilizes energy stores) and increases heart rate and blood pressure in times of stress ◦ Functions as a neurotransmitter ◦ Norepinephrine (10-20%) and dopamine function solely as neurotransmitters Catecholamine adrenal release is stimulated by stressors such as fear and pain.
  20. Adrenal catecholamine synthesis The adrenal medullary catecholamines are derived from the amino acid tyrosine.
  21. 4.Gonadal hormones(Sex steroids) Predominately produced by the adult male testes and female ovaries Adrenal cortex also produces small amounts of sex steroids Responsible for ◦ manifestation of primary and secondary sex characteristics ◦ Human reproduction Characteristics – steroid, lipid-soluble, slow effects, bound to carrier proteins (SHBG, albumin) Their secretion is under hypothalamus-pituitary-gonadal axis control
  22. Classes of female sex steroids Androgens ◦ Dehydroepiandrosterone (DHEA), DHEAS, testosterone, dihydrotestosterone (DHT), androstenedione ◦ The predominate adrenal androgens are DHEA and DHEAS Estrogens ◦ Estradiol, estrone Progestins ◦ Progesterone
  23. Female sex hormones Two different chemical types of steroid hormones are produced and secreted by the ovary in non pregnant women. ◦ Estrogen and progesterone During pregnancy, the same hormones are produced by the ovary, but in different proportion. The placenta also makes the hormones that are necessary for the maintenance of pregnancy. ◦ Estrogen, progesterone, HCG, lactogen This production is under control of ◦ hypothalamus(GnRH)→Pituitary(FSH,LH)→ovary/placenta (female sex steroids)
  24. Estrogen Originate in the ovarian follicles and in the placenta during pregnancy Function ◦ Participate in the menstrual cycle ◦ development and maintenance of the reproductive organs and secondary sex characteristics. Three clinically important estrogens: C18 steroid ◦ Estradiol(E2): major hormone in non-pregnant ◦ Estrone(E1) ◦ Estriol(E3): major hormone in pregnant
  25. Estradiol The principal and most potent estrogen It exists in a reversible state with estrone (with weaker biologic action), but it must be converted into E1 before it is degraded. ◦ Estradiol (E2) ↔ Estrone (E1) → Estriol(E3) → degradation Plasma E2 levels ◦ Useful for the investigation of women with menstrual difficulties To ascertain wether a problem is of pituitary or ovarian origin. ◦ Measurement of pituitary tropic hormones, FSH and LH
  26. Estriol(E3) It has no hormonal activity Produced in relatively large quantity during the last trimester of pregnancy by the placental conversion of fetal adrenal steroids. Its concentration in urine or plasma of pregnant women provides indication of fetal well being (fetoplacental viability) ◦ Sudden drop in estriol concentration or output is a danger signal of fetoplacental dysfunction.
  27. Progesterone It is a C21 compound and chemically more closely related to the adrenal steroids. It is an intermediate in the production of adrenal steroids. Formed in the corpus luteum, the body that develops from the ruptured ovarian follicle. Function ◦ Stimulates the uterus to undergo changes that prepare it for implantation of the fertilized ovum, ◦ Suppresses ovulation and secretion of pituitary LH. ◦ If pregnancy occurs, the secretion of progesterone by the corpus luteum and by the placenta suppresses menstruation for the duration of the pregnancy.
  28. Placental hormones Function of placenta: providing nutrients to the developing embryo and removing its waste products Additionally in the pregnant women it serves as an endocrine organ ◦ Produce ◦ Estrogen ◦ Progesteron ◦ chorionic gonadotropin (hCG) ◦ lactogen.
  29. Human chorionic gonadotropin (hCG) It is a glycoprotein composed of 2 chains, alpha and beta. Alpha polypeptide chain is identical to the alpha chain on many other hormones including TSH, LH and FSH. The beta chain is unique in hCG so is the speciificity for immunoassay techniques. The action of hCG is similar to that of LH ◦ It stimulate the corpus luteum to produce progesterone. ◦ Progesterone helps to maintain the pregnancy by preventing menstruation.
  30. Clinical significance of hCG For diagnosis of pregnancy ◦ The detection of hCG in urine or serum is the basis of current tests for pregnacy. ◦ The most sensetive can detect pregnacy with in 5 to 7 days after conception. ◦ The antibody used for quantitation of serum hCG should be specific to β-hCG in order to avoid cross reactions,
  31. Human placental lactogen It is a protein hormone that is structurally, immunologically and functionally very similar to growth hormone and prolactin HPL appears to act in concert with HCG to stimulate estrogen and progesterone synthesis by the corpus luteum. It stimulates development of the mammary gland (similar to prolcatin) Has somatotropin actions similar to those of growth hormone. ◦ it increases maternal plasma glucose levels and mobilization of free fatty acids and promotes positive nitrogen balance.
  32. Male sex hormones The male gonads are the testes. They have a double function: ◦ To produce and secrete the male hormone, testosterone ◦ To produce the spermatozoa ◦ Essential for fertilization of the ovum in the reproductive process. The testes are part of a hypothalamic-pituitary-gonadal axis. ◦ FSH stimulate spermatogenesis, ◦ LH stimulate the production of testestrone by interstitial (Leydig’s) cells. ◦ Both LH and FSH suppressed by high levels of testosterone
  33. Testosterone The most potent naturally occurring androgen. Function ◦ Promote growth of secondary sex organs ◦ It causes growth and development of the male reproductive system, prostate, and external genitalia. ◦ Promotes muscular and skeletal growth and is protein anabolic. Transport • 80% by plasma globulin • 17% by albumin • < 3% unbound, active hormone.
  34. Testosterone cont’d All of the testosterone in males is derived from the testes; the contribution of the adrenal cortex is negligible. Plasma testosterone levels are much lower in women, usually only 5% of those found in men. ◦ Testosterone in women arise from the tissue conversion of androgens. Plasma testosterone concentration is a good way of studying hypogonadism and hypergonadism. The role of the pituitary has to be assessed to determine whether an abnormality is primary to testes or secondary to an LH deficiency or excess.
  35. Testosterone cont’d Increased concentration of testosterone ◦ Testicular carcinomas ◦ Abnormalities of pituitary gonadotropin of males ◦ In female ◦ Virilism: development of male physical characteristics(depening of voice, breast atrophy, increased hair growth) ◦ Hirsutism: growth of body hair in male like pattern Decreased plasma testosterone can be due to: ◦ Defects associated with testis ◦ Defects associated in pituitary ◦ Chromosomal abnormalities of sex hormones.
  36. Methods of Sex Steroid Analysis Estrogens and testosterol ◦ RIA ◦ Reference Ranges vary with method and timing of female cycle More useful if tested along with FSH and LH
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