Hormones - female and male Flashcards
Describe the major hormones of male reproduction (GnRH, FSH, LH, and feedback)
- GnRH released from hypothalamus causes release of LH, FSH from anterior pituitary
- LH stimulates Leydig cells to cause conversion of cholesterol to testosterone (T) and subsequent release
- FSH stimulates the Sertoli cells and spermatogenesis
- Feedback:
Testosterone from Leydig cells inhibits GnRH and LH release
Inhibin from Sertoli cells inhibits FSH release
Describe the targets and MOA of testosterone in the male.
After being released by the Leydig cells, testosterone (T) is carried by sex-steroid-binding globulin (SSBG) to its targets (98% is protein-bound; can also be carried by albumin but it has lower affinity). Once inside the androgen responsive cells T is converted to DHT (or not), binds to the AR, dimerizes, and has 2 effects:
1. genomic - goes to nucleus to initiate RNA transcription to increase protein synthesis for PSA, growth, survival
2. non-genomic - second messenger cascade of phosphorylation, lipid mediators, IC Ca, etc.
Targets:
- Sertoli cells: stimulates spermatogenesis
- Maintains genital tract; T–>seminal vesicles and DHT–> prostate
- Induces 2ndary sex characteristics, aggression (?), stim. protein anabolism, regulates bone growth, required for sex drive
Estrogen production in male - how, where, why, how much?
- cholesterol converted to T, then to estradiol by the enzyme aromatase
- mostly in liver (80%), also testes, muscle, brain, fat
- estradiol is necessary for male fertility during reproductive age; it also helps to controls spermatogenesis
- 20% of that in females; increased with age/obesity
List the estrogens from strongest to weakest
E1- 17B-estradiol (major estrogen, strongest)
E2- Estrone
E3- Estriol (weakest)
Progesterone production by the ovaries:
List the cellular producers, key enzyme, and regulation.
::Cellular producers:
Theca cells
Granulosa cells (follicular phase)
Corpus luteum (major source post-ovulation)
::Key enzyme: cholesterol desmolase [aka CYP11A1]
(cholesterol —> pregnenolone, precursor for progesterone)
::Regulation: LH
Estrogen production by the ovaries:
List cellular producers, precursors, key enzymes, and regulation.
\::Cellular producers: Granulosa cells (follicular phase) Corpus luteum (luteal phase)
::Precursors: Pregnenolone, progesterone, androgens (androstenedione)
::Key enzymes:
Theca cells: cholesterol desmolase (produces precursor, pregnenolone)
Granulosa cells: 17B-hydroxysteroid dehydrogenase (androstenedione–> testosterone)
Aromatase (testosterone—> estrogen)
Regulation: LH (theca cells) and FSH (granulosa cells)
Describe the functions of granulosa cells.
- Nourish oocyte
- Secrete chemical messengers that influence the oocyte and theca cells
- Secrete antral fluid
- Site of action of estrogen and FSH in the control of follicle development during early and middle follicular phases
- Express aromatase
- Secrete inhibin, inhibiting FSH secretion
- Site of action for LH induction of changes in oocyte and follicle culminating in ovulation and formation of corpus luteum
Which hormones peak during ovulation?
LH, FSH, and…
Estrogen - rises and peaks just before ovulation which stimulates the release of FSH and LH; stays high during ovulation as well
Describe the negative feedback mechanism on the hypothalamo-pituitary-gonadal axis during the early and middle follicular phases.
FSH and LH stimulate estrogen production by follicular cells.
Estrogen, at low concentrations, feeds back on the anterior pituitary to inhibit FSH and LH production.
Describe the positive feedback mechanism on the hypothalamo-pituitary-gonadal axis during the midcycle (immediately before ovulation).
Estrogen, at high concentrations, feeds back
1) on the hypothalamus to secrete more GnRH and
2) on the ant. pit. to upregulate GnRH receptors, and increases secretion of FSH and LH (ovulation surge —> ovulation of mature oocyte)
Describe the negative feedback mechanism on the hypothalamo-pituitary-gonadal axis during the luteal phase.
During the luteal phase, progesterone (the major hormone during this time, since others peaked during ovulation) negatively feeds back on the ant. pit. to inhibit secretion of FSH and LH.
Briefly describe how chemical contraceptives work.
Prevent ovulation by negatively feeding back on the ant. pit. to suppress FSH and LH secretion, thus preventing the ovulation surge.
::low dose of estrogen
::Progesterone
- suppress ovulation, prevent implantation, increase viscosity of cervical mucus
How is estrogen transported in the blood?
Like all steroid hormones, bound mostly to steroid hormone binding globulins. Beta globulin (high affinity) Albumin (low affinity) 98% bound 2% free estrogen
Describe the effects of estrogen on target tissues such as Uterus, ovary, vagina, fallopian tubes, breast, brain/ant. pit.
1) Genomic- (long-lasting effects)
2) Non-genomic (rapid)
Uterus, Ovary, breast: stimulates growth Uterus, vagina: maturation Uterus: maintenance during pregnancy Fallopian tubes: stim. ciliary activity Brain/ant. pit. : feedback on FSH, LH secretion. Stimulates prolactin secretion
Describe the effects of estrogen on target tissues such as Bones, liver, heart, and blood vessels.
Bones: Regulates growth, preserves bone density, prevents osteoporosis.
Liver: Regulates cholesterol production, decreases LDL
Heart: cardioprotective
BVs: Anti-atherosclerotic effects, reduces plaque formation
Note: a recent study showed the following with regards to exogenous estrogen +/- progesterone administration, post-hysterectomy:
1) No effect on the incidence of coronary heart dz
2) Reduced risk of hip fx
3) no increased risk of breast cancer
4) slight increase in stroke risk
