The Sex Hormones & Reproductive Systems (6)

The Sex Hormones & Reproductive Systems (6)

The Male Reproductive System

The male reproductive system Lumen) Sperm Scrotum ~300 lobules Sertoli cell Leydig cell Testosterone Testes : - produce sperm cells (seminiferous tubule) - secret testosterone (Leydig cell) Scrotum : - protect testes and maintain the temp. Epididymis : - storage sperm cells (for 40-60 days) - absorb un-ejaculated sperm

Sertoli cell & spermatogenesis Functions of Sertoli cells Maintenance of the blood-testes barrier Nourishment of developing germ cells Production of seminiferous tubular fluid Removal of damaged germ cells Synthesis of androgen-binding protein (ABP) Synthesis of inhibin

enzymes used to dissolve a path to penetrate the egg gene produce ATP for sperm motility. Fate of sperm cells: - viable for 2 days (egg: 12-24 hr) - only one sperm fertilizes the egg

Hypothalamic-pituitary-testicular axis Leydig cells are primary endocrine cells of testis synthesize and secrete testosterone T-SHBG Peripheral conversion into DHT (genital skin, prostate) E2 (adipose) helps spermatogenesis SHBG: sex hormonebinding globulin Dihydrotestosterone (DHT); non-aromatizable androgen

Effects of testosterone (T) Direct (T) or indirect (DHT) actions of testosterone Sertoli cell function

Effects of exogenous androgen administration Exogenous administration of testosterone (or androgenic analogue) Causes sterility in some cases of steroid abuse in men Possible strategy for developing a male oral contraceptive

Male reproductive tract Contiguous lumen : epididymis (head, body, tail) vas deferens ejaculatory duct prostatic urethra membranous urethra penile urethra Functions of the male reproductive tract Sperm maturation Sperm storage and emission Production & mixing of sperm with seminal contents Erection and ejaculation

Function of male reproductive tract (1) 1. Sperm maturation Sperm maturation in the epididymis (~ 1 month) Secretion of epididymis Decapacitation of spermatozoa prevent acrosome reaction before contact with egg 2. Sperm storage and emission Sperm are stored in epididymis & vas deferens for several months Emission : emptying of vas deferens contents into prostatic urethra : sympathetic stimulation during sexual intercourse peristaltic contraction of vas deferens propel sperm into prostatic urethra (emission) ejaculation

Function of male reproductive tract (2) 3. Production & mixing of sperm with seminal contents Secretion of seminal vesicles 60% of seminal vol. provide fructose secrete semenogelins (induce coagulation of semen after ejaculation) Alkaline secretion of prostate 30% of seminal vol. high in citrate, Zn, spermine, acid phosphatase prostate-specific antigen (PSA; a serine phosphatase) liquefies coagulated semen after a few min. phosphate & HCO 3 - (ph buffer) Secretion of bulbourethral gl. (or Cowper s gl.) before emission & ejaculation in response to sexual excitement high in mucus; lubricates, clean & buffer urethra 4. Erection and ejaculation Reflex arc (penis sensory pudendal n. sympathetic motor n. smooth muscle of reproductive tract)

Erection Erection is a neurovascular event. 3 erectile bodies: 2 corpora cavernosa & 1 corpus spongiosum

Erection Sexual arousal cavernous nerve (nitrergic) & helicine a. endothelium release nitric oxide (NO) vascular smooth muscles of helicine arteries activate guanylate cyclase increase cgmp/decrease [Ca 2+ ]i vasodilation blood flow into cavernous spaces (penile vasocongestion) erection press veins reduce venous drainage keep erection (e.g. Viagra)

The Female Reproductive System

The female reproductive system Two important functions of ovary: 1) Oogenesis 2) Secretion of hormones Female reproductive tract (oviducts, uterus, cervix, vagina, external genitalia) outer cortex within cellular stroma, ovarian follicles reside inner medulla neurovascular elements

Fate of ovarian follicles ( 초경 ) (~37 년간배란수 )

Ovarian cycle Ovarian Cycle During each ovarian cycle, up to 20 primordial follicles are activated to begin the maturation process, but usually only one reaches full maturity, the remainder regress The ovarian cycle can be divided into 3 phases: 1. Follicular phase From many primordial follicles one Graafian follicle develops. 2. Ovulatory phase The Graafian follicle is released. 3. Luteal phase The corpus luteum and corpus albicans are produced.

Oogenesis & ovarian cycle Life history of follicle 1. Resting primordial follicle 2. Growing preantral (primary & secondary) follicle 3. Growing antral (tertiary) follicle 4. Dominant (preovulatory, Graafian) follicle 5. Dominant follicle within the periovulatory period 6. Corpus luteum 7. Degenerating corpus luteum Each cycle, 15~20 Graafian follicles (2~5 mm) form; one grows and others undergo atresia. Ovulation Follicle Corpus luteum progesterone + estrogen Luteal degeneration New cycle

Hormone secretion from ovarian follicles granulosa cells & thecal cells are endocrine cells Basal lamina LH surge 에대한반응성유지토록해줌 Granulosa cell Thecal cell

Hormonal interaction during follicular phase of ovarian cycle LH GnRH FSH FSH follicular growth (hypertrophy & hyperplasia of granulosa cells) Granulose cell estrogen (E) secretion stimulate further GnRH secretion increase LH & FSH secretion from pituitary Granulosa cell secrete E paracrine action increase number of E-R & FSH-R of granulosa cell enhance growth promoting action of FSH on granulosa cell follicle grows it secrete more E augment action of FSH FSH & E increase number of LH-R of granulosa cell granulosa cell secrete progesterone increase circulating progesterone level

Hormonal control during the ovarian (menstrual) cycle Follicular phase Luteal phase Ovulatory phase

Ovulation

Corpus luteum After ovulation; corpus hemorrhagicum RBC & debris are removed corpus luteum Corpus luteum secrete progesterone & estrogen Corpus luteum of menstruation: live ~14 ± 2 days unless rescued by human chorionic gonadotropin (hcg), which is originated from an implanting embryo luteolysis If rescued, corpus luteum of pregnancy will remain viable during the pregnancy (~9 months) Corpus hemorrhagicum

Hormonal control of ovarian (menstrual) cycle

Hormonal changes during menstrual (ovarian) cycle

FSH granulosa stimulation estrogen synthesis GnRH FSH, LH High estrogen LH surge antral fluid + ovarian wall degeneration ovum release (ovulation) After ovulation, LH stimulates granulosa cells to form corpus luteum (luteinization) early luteal phase progesterone (P4), estrogen (E2), inhibin from luteum LH, FSH (negative feedback) Late luteal phase luteum degenerates progesterone, estrogen from luteum LH, FSH new cycle (new follicles begin to develop)

Follicular phase: estrogen endometrial proliferation and progesterone receptor synthesis Luteal phase: progesterone + estrogen endometrial blood vessels, glycogenholding glands swelling

Oviduct Peristalsis & cilia transport cumulusoocyte complex Fertilization (=oviduct) Main function of the oviduct: Ciliated epithelial cells transport cumulus-oocyte complex Capture & transfer of the cumulus-oocyte complex to ampullaryisthmus juction fertilization take place Sperm storage (viable sperm for 5~7 days) Provide nutrients to preimplantation embryo

Uterus 2/3: lost during menstruation Main function of the uterus: Assist sperm movement Provide a site for attachment & implantation of blastocyst Protect the implanting embryo Provide a maternal side of the mature placental architecture Grow fetus Strong muscular contraction to expel the fetus Uterine endometrium

Menstrual cycle of the uterine endometrium Luteum die withdrawal of progesterone shedding (vol. = 25~35 ml) Proliferation by estrogen Progesterone : inhibits further endometrial growth induce secretion of uterine gland nutrition, blastocyst viability inhibits myometrial contraction

Biology of estrogen Estrogen (estradiol-17b) stimulates sex organ growth, 2º sex characteristics bone: closure of epiphysial plates of long bone, bone anabolic (calciotropic effect), bone formation, bone breakdown (prevention of osteoporosis) improve circulating lipoprotein profiles promote vasodilation (NO production ) healthy & smooth skin neuroprotective decrease adipose tissue

Pregnancy, Parturition & Lactation

Fertilization

Fertilization & implantation Progesterone Estrogen Rescue of CL by hcg

Placental endocrinology

Placental hormones (1) 1. hcg (human chorionic gonadotropin): Produced by syncytiotrophoblast hcg is detectable within maternal serum <24 hr of implantation Maternal serum hcg level increases and peak at ~10 weeks Structurally similar to LH binds with high affinity to LH-R hcg stimulates LH-R of corpus luteum prevents luteolysis maintains lutealderived progesterone during the first 10 weeks continued growth of endometrium Stimulates steroid synthesis in the fetal adrenals Stimulates fetal testes testosterone release internal genitalia growth Suppresses maternal immune system reduce the immunorejection of the fetus Responsible for the nausea of morning sickness ( 입덧 ). Maternal hcg level Pregnancy test

Placental hormones (2) 2. Progesterone : Placenta produces a high amount of progesterone (~ 6 wks) enters into maternal circulation Switch from corpus luteum-derived progesterone to placental-derived progesterone (luteal placental shift) is completed at ~ 8 weeks Thickens endometrium Maintains a quiescent myometrium and a pregnant uterus Induces breast growth and differentiation 3. Estrogen : Produced by syncytiotrophoblasts (hcg stimulation) Synthesis of E requires fetal adrenal gland (fetoplacental unit) Maternal estrogen levels increase throughout pregnancy Increases uteroplacental blood flow & uterus size Increase breast growth, lactotrope size & number Enlargement of external genitalia & relaxation of pelvic ligament facilitate delivery

Placental hormones (3) 4. hpl (human placental lactogen): Pregnancy insulin-resistant state hpl shifts maternal energy metabolism from anabolic to catabolic state Pregnancy aggravates existing DM or can produce gestational DM Human placental lactogen

Parturition post. pituitary (PGF2a & E2) Placental CRH

Lactation (1) Dopamine cell Dopamine

Suckling, baby sound Lactation (2) estrogen Development of the breast is stimulated by estrogen, progesterone, hpl, and prolactin. Up to 1.5 L/day milk is produced Suckling Prolactin Milk synthesis & secretion into alveoli Prolactin lactational amenorrhea Suckling, baby crying sounds hypothalamus oxytocin myoepithelial contraction milk let-down