Physiology Block 3 Week 13 Female Reproductive Endocrine Flashcards Preview

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Flashcards in Physiology Block 3 Week 13 Female Reproductive Endocrine Deck (45)
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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



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:


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



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

1. 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

2. Loss of progesterone and estrogen negative feedback

Results in:
--FSH (primarily) and LH

3. 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

4. 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

1. LH surge stimulates ovulation
--formation of corpus luteum (what's left)
--dominant follicle stops making estrogen, terminating LH surge

2. Corpus luteum produces progesterone
--inhibits FSH and LH secretion

3. 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

1. LH binds receptor on theca cell
2. Androgens produced
3. Androgens diffuse into granulosa cell
4. FSH acts on granulosa cell and stimulates aromatase activity
5. Conversion of androgen to estrogen

When follicle becomes more dominant, granulosa cell expresses LH receptor

1. LH binds receptor on granulosa cell
2. Production of progesterone (from cholesterol)
3. Progesterone shuttled into Theca cells
4. In Theca cells, progesterone converted to androgen
5. 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

-Lining: increased cilia formation and activity (want to be ready to transport egg if fertilized)
-Muscular Wall: increased contractility

-Endometrium: increased proliferation (growth)
-Myometrium: increased growth and contractility
-Cervical Glands: watery secretion (allows sperm to get in)

-increased epithelial proliferation
-increased glycogen deposition


Effect of Progesterone on Reproductive Tract

Progesterone predominates during luteal (secretory--slow things down) phase

-Lining: increased secretion (help get to uterus)
-Muscular wall: decreased contractility

-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)

-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



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?

-Fetal Adrenal function
-Fetal Livers function


How do the concentrations change in pregnancy?

hCG peaks in the first trimester

Placenta makes most of the estrogen and progesterone during 2nd and 3rd trimester (unregulated production)
--hCG wanes because corpus luteum no longer necessary

Estrogen and Progesterone increase as placenta gets bigger


Changes of Anterior Pituitary hormones during pregnancy:


GH--no change

LH and FSH--low during pregnancy bc estrogen and progesterone inhibit menstrural cycle

ACTH--no change

TSH--wobbles because maternal TH important in developing fetus (1st trimester):
-TBG increases
-reaches nadir (1st trimester) then plateaus

Prolactin--increases steadily during pregnancy bc mammary glands stimulated so tissue is there to produce milk after parturition


Changes of placental proteins during pregnancy:


hCG--(homology with FSH and LH) increases, then declines

hPL--(homology with GH) increases steadily.
-thought to contribute to insulin-resistant state bc want maternal blood glucose to go up a little to feed baby

CRH--burst at end may contribute to onset of parturition
--stimulates ACTH


Changes of fetoplacental estrogen during pregnancy

All increase!

Estriol (E3) increases most
Estradiol (E2)
Estrone (E1)


Changes of fetoplacental androgens during pregnancy:


Fetus and placenta can make androgens

--most from maternal adrenal glands


Androstenedione--small increase


Changes in thyroid hormones during pregnancy:

-Total T4
-Total T3

Estrogen stimulates production of thyroid binding globulin (TBG)
As estrogen increases, amount of TBG increases

Total T4 and T3 increase because there are more binding sites
--happens SLOWLY
--reaches a new baseline/steady state
Ex. Person who gets packed RBC has same PO2. RBC suck up O2, BUT lungs suck in a little more O2. The moles O2 taken in is small compared to O2 bound to Hb

Free TH never really changes
--conceptually TH goes down, but happens so slowly over months that will never be able to detect it