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 –Lipoproteins De Novo synthesis –Side-chain cleavage Production of pregnenolone (P 5 ) –From 27-C molecule to 21-C molecule

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

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

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

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

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

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

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

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

Gross anatomy of male reproductive organs

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

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

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

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

Gross anatomy of female reproductive organs

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

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

Functional unit of the endometrium –Functionalis Proliferation Secretion Degeneration Site of implantation –Basalis Regenerative unit

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

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

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

Action of progesterone –Increase in cytoplasm of stroma Psuedodiciduation

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

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

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

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