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Steroid hormone synthesis

Steroid hormone synthesis. Steroidogenesis. Conversion of cholesterol into hormones Chemical modification Ring formation Reduction of ketone to alcohol Structural modification Removal of carbon side-chains. Site of steroidogenesis. Mitochondria Uptake of cholesterol Circulation

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Steroid hormone synthesis

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  1. Steroid hormone synthesis

  2. Steroidogenesis • Conversion of cholesterol into hormones • Chemical modification • Ring formation • Reduction of ketone to alcohol • Structural modification • Removal of carbon side-chains

  3. Site of steroidogenesis • Mitochondria • Uptake of cholesterol • Circulation • Lipoproteins • De Novo synthesis • Side-chain cleavage • Production of pregnenolone (P5) • From 27-C molecule to 21-C molecule

  4. Cytoplasm • Conversion of P5 to progesterone (P4) • C-21 steroids • Conversion of progestigens to androgens • C-21 steroids to C-19 steroids • Conversion of androgens to estrogens • C-19 steroids to C-18 steroids • Armatization of the sterol ring

  5. Steroidogenic cells • Male • Leydig cells • Testosterone production • Sertoli cells • Estradiol production • Females • Theca cells • Androgen production • Granulosa cells • Estradiol production • Progesterone production by both theca and granulosa cells

  6. Two-cell, two-gonadotropin theory • Ovarian steroidogenesis • LH acts on theca cells to produce androgens • FSH acts on granulosa cells to produce estradiol using thecal androgens • FSH • Essential for normal granulosa cell development and function • Expression of LH receptors in large follicle

  7. LH Ovulation + + + FSH Pattern of follicular development and changes in blood hormone concentrations

  8. Role of gonadotropins • Production of cAMP • Activation of protein kinase A pathway • Increased binding of steroidogenic factor-1 (SF-1) to DNA • Transcription factor • Activation of genes involved in steroidogenesis

  9. Role of gonadotropins • Increased cholesterol uptake • Increased number of steroidogenic acute regulate protein (StAR) • Most critical step for androgen synthesis • Increased enzyme activity • Aromatase expression in the granulosa cells

  10. Action of steroid hormones • Development of reproductive organs • Fetal • Pubertal • Determinative • Adult • Regulatory • Regulation of gonadotropin secretion • Long feedback loop

  11. Role of androgens in male • Fetal life • Determinative action • Development of male genitalia • Defeminization and masculinization • Adult life • Essential for normal spermatogenesis • Development and function of accessory sex organs

  12. Gross anatomy of male reproductive organs

  13. Effects of androgens on the prostate gland and seminal vesicle • Production of seminal fluid • Differentiation of the prostate ducts • Blanching of seminal vesicles • Loss of androgen • Involution of gland • Loss of secretion

  14. Role of testosterone on spermatogenesis • Essential for normal spermatogenesis • Proper production of semineferous tubule fluid • Critical for normal sperm development • Nutrients to developing sperm cells • Controlled by testosterone in adults

  15. Intratetsicular concentration of testosterone • Much higher than in peripheral circulation • Critical for maintenance of spermatogenesis • Sertoli cell function

  16. Loss of testosterone • Reduced Sertoli cell function • Reduced semineferous tubule fluid production • Stage-specific effects • Later stages (7 and 8)

  17. Gross anatomy of female reproductive organs

  18. Role of estradiol and progesterone in female • Cyclic changes • Cyclic changes in ovarian structure • Cyclic changes in uterine structure • Follicular phase • High estradiol • Low progesterone • Preparation of reproductive tract for fertilization • Oviduct • Uterus

  19. Uterine endometrium • Mucosal lining of the uterus • Inner-most lining • Well-developed in human compared to other species • Placentation • Menstruation (shedding of endomertial tissue) • Spiral arteries • Hemorrhage (changes in blood flow) • Renewal of endometrium during each reproductive cycle

  20. Functional unit of the endometrium • Functionalis • Proliferation • Secretion • Degeneration • Site of implantation • Basalis • Regenerative unit

  21. Hormone-induced changes in endometrium • Cyclic in nature • Re-epithelialization • Menstrual-postmenstrual transition • Endometrial proliferation • Estradiol • Epithelial secretion • Estradiol and progesterone • Premestrual ischemia • Loss of blood supply to epithelia • Menstruation

  22. Role of estradiol • Proliferation of endometrium • Transcription and translation • Thickening of stroma • Mitosis • Stimulated by growth factors from stroma • Growth and differentiation • Increased metabolic activity • Expression of progesterone receptors

  23. Effects of progesterone • Differentiation of endometrium • Inhibition of estradiol-induced proliferation • Mediated by stroma • Secretion • Proteins • Critical for implantation

  24. Action of progesterone • Increase in cytoplasm of stroma • Psuedodiciduation

  25. Effects on other uterine tissues • Myometrium (smooth muscle) • Excitability and contraction • Depressed by progesterone • Increased by estradiol

  26. Menstruation • Absence of pregnancy • Initiation of endometrium remodeling • Alteration of extracellular matrix • Leukocyte infiltration • Death and removal of tissue • Regeneration of tissue

  27. Menstruation • Withdraw of steroid hormones • Constriction of arterioles and coiled arteries • Ischemia • Precedes bleeding • Bleeding • Relaxation of arteries • Induction of hypoxia-reperfusion injury (formation of hematoma) • Detachment of tissue fragments

  28. Effects of steroid hormones on female reproductive tract • Oviduct • Secretion of oviductal fluid • Nutrients for the oocytes • Sperm survival and capacitation • Early embryonic development • Cervix • Estradiol • Relaxation of muscle • Secretion of watery mucus • Progesterone • Tightening of muscle • Secretion of thick mucus

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