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Comprehensive Overview of Steroid Hormone Synthesis and Function

Explore the intricate process of steroidogenesis, from cholesterol conversion to hormone production, in various cells and its vital roles in male and female reproductive systems. Understand the actions of androgens and estrogen, and the impact of these hormones on reproductive organs.

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Comprehensive Overview of Steroid Hormone Synthesis and Function

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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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