Physiology Block 3 Week 13 Female Reproductive Endocrine Flashcards
(45 cards)
How is genetic sex determined?
Genetic sex is determined at conception
The lack of hormonal signals lead to female phenotype–required to develop male phenotype
What gene is leads to development of male phenotype?
H-Y antigen–encoded by SRY (sex-determining region of Y-chromosome)
In absence of testis, what is not developed?
In absence of testis, ovaries form
There is a lack of androgen production
- no testosterone or its conversion to DHT in target tissues
- no Mullerian inhibiting factor (induces regression of mullerian ducts)
Without these 2 hormones:
Wollfian ducts regress and Mullerian ducts develop into female reproductive tract
Follicle Growth in the ovary
Pre-antral follicle has ovum
Follicle developed inside Granulosa and Theca cells
Once developed ovulates egg and can be fertilized
What’s left after ovulation is the corupus luteum
- -produces primarily progesterone
- -if egg not fertilized and does not implant, corpus luteum dies
Atresia
At 6 months gestation, will have 7 million oognoia (potential ova)
Oogonia start to degenerate which continues until menopause
At birth, about 600,000 oogonia remaining
Pattern of hormones and oogonia from:
- Gestation
- Birth
- Puberty
Middle of gestation (fetus):
A burst of FSH and LH
Human chorionic gonadotropin (hCG) wanes
–important for stimulating oogonia
Birth (2-6 months): Lose hCG Another burst of FSH and LH -Males: stimulates testes to produce androgen -Females: unknown
Before Menarche (puberty):
Pituitary secretion of FSH and LH
–induces ovarian function to produce estrogen
–stimulates growth spurt (Growth Hormone)
Female Steroidogenesis
3 Estrogens:
- Estrone (E1)
- Estradiol (E2): estrogen of non-pregnant women
- Estriol (E3): estrogen of pregnant women
AROMATASE (A) necessary to convert androgen to estrogen
Androstenedione (A)–> E1
- -> E2
- -> E3 (liver)
Androstenedione–>Testosterone (A)–> E2
- -> E1
- -> E3 (liver)
Steroid Distribution in Plasma and Binding Proteins
Most steroids bound to a carrying protein–very little is free
Cortisol Binding Globulin (CBG)–cortisol only, no estrogen, some progesterone (cortisol precursor)
Sex-Hormone Binding Globulin (SHBG)–binds sex hormones (mainly androgens) testosterone and estrogen
Albumin–estrogen will bind albumin more than SHBG
What initiates puberty in females?
Hypothalamic GnRH and Pituitary gonadotropins (FSH and LH) are released in pulsatile manner
Body fat and intake of calories may stimulate puberty in girls
–Gymnasts, anorexic (refusal to eat), and bulemic girls fail to have menstrual cycle (amenorrhea)
Leptin (from adipose tissue) signals hypothalamus to increase GnRH pulses
Kisspeptin
Estrogen has negative feedback on hypothalamus and pituitary
–when high, prevents release of GnRH
Leptin (from adipose tissue) activates neurons that activate kisspeptin, which actives GnRH neurons to pulse
- -leads to increased FSH and LH release
- -leads to ovaries producing more estrogen
Female Puberty
Leptin activates kisspeptin, which activates pulsatile release of GnRH, which activates pituitary to make FSH (and a little later LH)
- FSH wakes up ovary follicles
- follicles increase estrogen production
Simultaneous development of breast/pubic hair and growth spurt
- -peak growth velocity is earlier in girls than boys
- -estrogen induces closure of growth plates in long bones
Last thing to develop is 28 day menstrual cycle
–If not having regular menstrual cycles by 16, need to be checked
Menstrual Cycle: Follicular Phase
- Death of corpus luteum due to:
- -no pregnancy
- -hCG not released by the trophoblast into maternal blood
Results in:
- -decreased progesterone (necessary for secretory phase of uterine cycle)
- -decreased estrogen
- Loss of progesterone and estrogen negative feedback
Results in:
–FSH (primarily) and LH
- FSH induces maturation of next group of follicles
- -a dominant follicle develops (from 6-12) and autonomously releases estrogen
Results in:
- -estrogen increase decreases FSH and LH via negative feedback
- -dominant follicle can survive loss of FSH and LH –atresia of non-dominant follicles
- When estrogen peaks induces hypothalamic-pituitary switch to positive feedback
- -estrogen stimulates a SURGE in LH (and to a lesser degree FSH)
- -LH surge required for ovulation induction
Menstrual Cycle: Luteal Phase
- LH surge stimulates ovulation
- -formation of corpus luteum (what’s left)
- -dominant follicle stops making estrogen, terminating LH surge - Corpus luteum produces progesterone
- -inhibits FSH and LH secretion - Corpus luteum dies if:
- -no pregnancy
- -no release of hCG from trophoblast into maternal blood
Generation of Positive Feedback-Induced LH surge
Early Follicular Phase:
- dominant follicle produces estrogen that acts LOCALLY to stimulate induction of FSH receptors on granulosa cells
- allows survival of FSH decrease
Mid-Follicular Phase:
Non-dominant follices have died due to FSH decrease
Local estrogen positive feedback induces:
-more FSH receptors
-LH receptors
-proliferation (division) of granulosa cells
Late Follicular Phase:
- follicle loaded with granulosa cells (proliferation)
- estrogen peaks in blood (due to increased granulosa cells), inducing positive feedback stimulation of LH and FSH leading to LH surge
- LH surge stimulates follicle to expel egg
All the cells left behind form corpus luteum, which produces progesterone
Interaction of Follicular Theca and Granulosa Cells
Production of estrogens
Theca cell:
- makes LH receptors
- no aromatase
Granulosa Cell:
- makes FSH receptors
- expresses LH receptors mid-cycle
- aromatase present
- LH binds receptor on theca cell
- Androgens produced
- Androgens diffuse into granulosa cell
- FSH acts on granulosa cell and stimulates aromatase activity
- Conversion of androgen to estrogen
When follicle becomes more dominant, granulosa cell expresses LH receptor
- LH binds receptor on granulosa cell
- Production of progesterone (from cholesterol)
- Progesterone shuttled into Theca cells
- In Theca cells, progesterone converted to androgen
- Androgen diffuses into granulosa cell for conversion into estrogen under FSH stimulation
Need both Theca and Granulosa Cells to produce estrogen
Effect of Estrogen on Reproductive Tract
Estrogen predominates during follicular (proliferative growth) phase
Oviduct
- Lining: increased cilia formation and activity (want to be ready to transport egg if fertilized)
- Muscular Wall: increased contractility
Uterus
- Endometrium: increased proliferation (growth)
- Myometrium: increased growth and contractility
- Cervical Glands: watery secretion (allows sperm to get in)
Vagina:
- increased epithelial proliferation
- increased glycogen deposition
Effect of Progesterone on Reproductive Tract
Progesterone predominates during luteal (secretory–slow things down) phase
Oviduct
- Lining: increased secretion (help get to uterus)
- Muscular wall: decreased contractility
Uterus
- Endometrium: increased differentiation and secretion (ready for implantation)
- Myometrium: decreased contractility (want uterus quiet rather than pushed out)
- Cervical Glands: Dense/viscous secretion (to prevent germs getting in or egg leaving)
Vagina
- increased epithelia differentiation
- decreased epithelial proliferation
Myometrial (Uterine) Cycle
Estrogen dominates proliferative (follicular) phase (11 days), so thickness of endometrium grows dramatically
Progesterone from corpus luteum (12 days) dominates secretory (luteal) phase and stimulates secretions so if fertilized egg comes along, endometrium is ready for implantation
If no implantation occurs or hCG present to rescue corpus luteum, it dies (end of luteal phase)
–progesterone and estrogen plummet
Menstrual phase (5 days)
- -uterine spiral artery supplying blood to endometrium vasoconstricts
- -endometrium dies and sloughed into menstrual bleed
Which of the following is an example of positive feedback?
A. Effect of progesterone on LH and FSH in luteal phase
B. Effect of estrogen on LH and FSH in the late follicular phase
C. Effect of estrogen on LH and FSH in early follicular phase
D. Effect of decreasing progesterone in the late luteal phase
B. Effect of estrogen on LH and FSH in the late follicular phase
How is corpus luteum rescued by hCG?
Follicular phase, estrogen predominates
Positive feedback of estrogen results in LH surge
–ovulation in 24 hours
–fertilization in 24 hours
Fertilization usually in oviduct (fallopian tube)
–begins development as works way to uterus
At uterus, now a blastocyts (Day 5)
- -implanted into myometrium (Day 7)
- -makes blood connection to maternal circulation
Placenta/trophoblast begins making hCG
- -looks like LH, FSH, TH due to alpha subunit (beta unit = activity)
- -goes into maternal circulation and rescues corpus luteum
Corpus luteum continues making estrogen and progesterone
–keeping FSH and LH low inhibits next menstrual cycle
hCG
Stimulates estrogen and progesterone release from corpus luteum
–inhibits GnRH (hypothalamus) and Anterior pituitary gonadotropin secretion (FSH and LH), which prevents next menstrual cycle during pregnancy
Stimulates continued growth of endometrium to nurture growing implanted embryo and fetus
Steroidogenesis in Trophoblast
Trophoblast implants into endometrium
- -takes up LDL (for cholesterol)
- -cholesterol converted to pregnenolone (mitochondria)
Pregnenolone converted to progesterone (SER) and secreted into maternal circulation
Also, pregnenolone passed to fetus
–taken up by fetal adrenal to make adrenal steroid end-products
Steroidogenesis in Plancenta
Placenta has lots of aromatase
Maternal adrenal testosterone converted to estradiol (E2) in trophoblast
Maternal adrenal DHEA converted to estrone (E1) in trophoblast
Fetal adrenal synthesizes DHEA (from trophoblastic prognenolone) and sulfates it in fetal zone
- -in fetal liver, DHEAS converted to 16-OH-DHEAS
- -converted to Estriol (E3)
Estriol used as a marker of fetal distress
- Fetal Adrenal function
- Fetal Livers function
Why is estriol used as a marker for fetal distress?
Assesses:
- Fetal Adrenal function
- Fetal Livers function
