Flashcards in Lecture 4+5 Deck (67):
Male parts that are dually innervated (para/symp):
Nerve that innervates penis:
Pudendal nerve. Somatic afferent and efferent.
Pathways of erectile regulation:
Parasymp: pelvic nerve.
Symp: right/left hypogastric nerves.
Somatic: pudendal nerve.
Parasympathetic component of erection:
Coordinated by corpus cavernosa and corpus spongiosum.
Corpora smooth muscle relaxes and allows increased inflow of blood. Parasymp post-gang release of ACh and NO.
ACh binds to M3 receptors on endothelial cells.
PLC pathway to make NO. NO diffuses to vascular smooth muscle to stimulate vasodilation.
Sympathetic component of erection:
Sympathetic tone decreases to allow relaxation. Don't want to cancel out parasymp.
Somatic component of erection:
Two kinds of striated muscle:
- Ischiocavernous: contracts during final phase of erection to increase cavernosa pressure above systemic arterial pressure.
- Bulbospongiosus: increases spongiosum engorgement by pumping blood from underlying penile bulb.
Coordinated peristalsis of vas deferens, seminal vesicles, prostatic smooth muscle.
Internal sphincter of bladder constricts to stop retrograde ejaculation.
Drugs to treat erectile dysfunction:
Sildenafil (Viagra), vardenafil (Levitral), tadalafil (Cialis).
Oral drugs that promote smooth muscle relaxation by preventing cGMP degradation. Highly selective and high affinity inhibitors of cGMP-specific phosphodiesterase 5.
Side effects of sildenafil:
Blue vision. cGMP is needed to see blue; viagra blocks cGMP breakdown.
Causes of retrograde ejaculation:
Drugs that interfere with sympathetic tone.
Interrupted innervation of vas deferens or bladder neck.
Treatment of retrograde ejaculation:
Sympathomimetic drugs (phentolamine, ephedrine, imipramine). Increase tone of vas deferens and sphincter.
Hilus of female reproductive system:
The place where the ovary cortex doesn't surround the medulla.
Frigging ovarian cycle:
Lecture 4/5, slide 14
Changes in gonadotropins during puberty:
GnRH becomes pulsatile and gonadotropins are harder to inhibit by estrogen. Hyp-pit axis gets resistant to inhibition by sex steroids. Gonadotropins are UNSTOPPABLE during adulthood.
Pulsatile GnRH release:
Once an hour. In early follicular phase, sensitivity is low and gonadotropin surge is small. In late follicular phase, sensitivity rises and gonadotropin surge gets bigger.
Halflife of GnRH:
Pulse generator for GnRH release:
Located in arcuate nucleus of hypothalamus.
Why is GnRH release pulsatile?
Pulsatile favours increased GnRH receptors in gonadotrophs. Continuous administration causes downregulation of GnRH receptors.
Granulosa cell function during luteal phase:
Granulosa cells can do everything that Theca cells can! wow. cool.
GnRH receptor replenishment:
Receptor is internalized and partially degraded in lysosomes. A part of the receptor is then shuttled back to the surface for reuse.
Negative feedback control of ovarian steroids: most of the cycle.
Estrogen from ovaries inhibits hypothalamus and ant pit gonadotrophs at high and low concentrations.
Progestins from ovaries inhibit hypothalamus and ant pit gonadotrophs only at high concentrations.
Positive feedback control of ovarian steroids: end of follicular phase.
At high enough estrogen concentrations, hyp-pit axis reverses sensitivity to estrogen. Estrogen now stimulates GnRH gonadotrophs, leading to LH surge.
What molecules inhibit arcuate nucleus? preoptic area?
Arcuate nucleus: opiates
Preoptic area: GABA
Negative feedback control of ovarian steroids by inhibins:
Inhibit FSH from ant pit gonadotrophs at mRNA level. No effect on LH. Decreases androgen production, which decreases estrogen.
Positive feedback control of ovarian steroids by activins:
Promotes FSH transcription. No effect on LH. Stimulates estrogen.
Therapeutic uses of GnRH:
To increase gonadotropin, treat with pulsatile. To inhibit gonads, treat with continuous administration.
Kallman syndrome: what is it? treatment?
Disordered migration of GnRH during embryonic development. Causes hypogonadotropic hypogonadism and anosmia.
Treat with pulsatile.
Endometriosis: what is it? treatment?
Abnormal presence of endometrial tissue outside of uterine cavity. Tissues respond to estrogen and cause complications.
Treat with continuous GnRH analog to inhibit GnRH receptor replenishment. Endometrial tissue starves to death.
Smooth muscle tumour of uterus.
Treat with continuous administration. Growth is estrogen-dependent - tumour starves to death.
Two-cell two-gonadotropin of estrogen biosynthesis: why?
Superficial theca cells and theca-lutein cells can convert cholesterol into adrenal androgens, but are missing aromatase.
Deeper granulosa cells and granulosa-lutein cells can convert (T) into estrogen, but lack enzymes needed to make adrenal androgens.
How granulosa cells obtain cholesterol: follicular vs luteal phase
Follicular: only the outside is vascularized, so cholesterol is synthesized de novo.
Luteal: vascularization increases, so cholesterol is taken from blood.
Gonadotropin receptors on theca cells and granulosa cells during luteal phase:
Theca have LH receptors.
Granulosa have LH and FSH receptors.
Two-cell two-gonadotropin model of estrogen biosynthesis: who does what, when?
Follicular phase: follicle synthesizes estrogens.
Luteal phase: corpus luteum synthesizes estrogens.
Two-cell two-gonadotropin model of estrogen biosynthesis: steps (6)
1. LH stimulates theca cell (by AC pathway) to increase synthesis of LDL receptor and SCC enzyme.
2. Theca cell makes androstenedione.
3. Androstenedione diffuses to granulosa cells.
4. FSH stimulates granulosa cell (by AC pathway) to produce aromatase.
5. Aromatase converts androstenedione to estrone, then 17-beta-HSD converts estrone to estrogen OR 17-beta-HSD converts androstenedione to (T), then aromatase converts (T) to estrogen.
6. Estrogen diffuses to bloodstream.
Best environment for estrogen synthesis:
Low concentration of weak androgens from theca cells. If concentration is too high, weak androgens get converted to stronger ones. Strong androgens cannot be converted to estrogen, and they also inhibit LH receptor synthesis.
Function of aromatase:
Convert androgens to estrogens.
Functions of estrogen:
Stimulates cell proliferation and sex organ growth.
60% bound to albumin.
38% bound to SHBG.
SHBG in men vs women:
Estrogen stimulates SHBG synthesis - 2x higher in women than men.
Functions of progestin:
Stimulate glandular secretion in reproductive tissue.
In latter half of cycle, induces final maturation of endometrium for implantation.
When in menstrual cycle do surges occur?
LH, FSH, estrogen, progesterone
LH: before ovulation.
FSH: at ovulation.
Estrogen: before ovulation, in the middle of luteal phase.
Progesterone: in the middle of luteal phase.
Endometrial cycle in bb:
Placental estrogens cause endometrial development.
At 32 weeks, glycogen deposition and matrix edema appear.
After delivery, endometrium regresses. At 4 weeks after birth, glands are atrophic and unvascularized.
Wait for puberty.
Menstrual phase: what happens? (not preg)
Corpus luteum dies.
Pattern of estrogen receptors:
Increase during follicular, decline after ovulation.
Proliferative phase: what happens?
Estrogens induce synthesis of endometrial growth factors and progestin receptors in endometrium.
Zona basalis freaks out because now it's naked, so it starts regenerating the endometrium. Stromal and glandular epithelium divide a lot for 3 days.
Pattern of progestin receptors:
Peaks with estrogen.
Progesterone's antiestrogen effects during proliferative phase:
Converts estrogen to less active estrone. Inhibits epithelial cell proliferation, but promotes proliferation of the endometrial stroma.
Early secretory phase: what happens?
Progesterone stops proliferative phase by antiestrogen effect. Also makes the endometrium baby-welcoming.
Predecidualization (secretory phase):
9-10 days after ovulation, stromal cells around uterine arteries enlarge and get a buncha Golgi and ER. Predecidual cells differentiate into zona compacta and zona spongiosa.
Functional layer of endometrium vs... other:
Functional layer: zona compacta and spongiosa. They hang out with the baby and are shed after pregnancy/when not pregnant.
Other: zona basalis is around all the time. Makes new compacta and spongiosa every month.
Middle secretory phase: what happens?
Predecidualization, growth of endometrium.
Late secretory phase: what happens?
Estrogen and progestins peace out and everything dies. As cells break, broken lysosomes help break down more endometrium.
Why doesn't menstrual blood clot?
Fibrolysins from necrotic endometrial tissues.
Regimens of birth control:
Biological action of birth control pills:
Decrease GnRH at hyp and ant pit gonadotrophs. Suppress LH and FSH.
Oral birth control decreases risk of: (6)
Ovarian cancer, endometrial cancer, ovarian retention cysts, ectopic pregnancy, pelvic inflammatory disease, benign breast disease.
Oral birth control increases risk of: (7)
Benign liver tumours, cholelithiasis, hypertension, heart attack, stroke, deep-vein thrombosis, pulmonary embolus.
Menopause: progressive loss of ovarian follicular units
At 20 weeks of gestation: 6-7 million germ cells.
At birth: 1-2 million.
At puberty: 400 000.
Average menopause age:
Average # of ovulated oocytes:
Biology of menopause:
Ovarian steroids decrease, gonadotropins increase. FSH is no longer inhibited by estrogen or inhibin.
Young women vs older but premenopausal women:
Older have lower estradiol and decreased luteal function.
Menopausal syndromes: (8)
Short-term memory loss
Loss of libido
Menopausal physical changes: (7)
Atrophy of vaginal epithelium
Changes in vaginal pH
Decrease in vaginal secretions
Decrease in circulation to vagina/uterus
Loss of vaginal tone
Cardiovascular disease, osteoporosis, Alzheimers.
Four stages of female sex response:
Libido increases around ovulation because of increased androgens.
Pathway of female sex response:
Parasympathetic fibres from sacral plexus to erectile tissue.
ACh -> vasodilation -> enlargement of clitoris.