Female Physiology Review

Question 1

• What stimulates oogonia within the ovaries?
• What happens between 2 - 6 months post-natally?
• What is secreted just before the first menstrual cycle begins?

Answer 1

• hCG (human chorionic gonadotropin) from the placenta and fetal FSH and LH dramatically stimulate the production of oogonia within the ovaries
• Between 2 and 6 months of post-natal age:
  
  • FSH and LH peak again
  • exact purpose of this is in females is not well established since the ovaries don’t respond
  • in males, this burst of gonadotropins does stimulate the testes to produce androgens
• Before the first menstrual cycle (menarche):
  
  • pituitary secretes FSH and LH → induces ovarian function

Question 2

• How do the enzymes for DHEA and androstenedione compare to the enzymes used in the adrenal cortex?
• How many estrogens are there?
  
  • What are the differences?

Answer 2

• Pathways to DHEA and androstenedione are catalyzed by the same enzymes as in the adrenal cortex
• There are 3 estrogens:
  
  • produced from androgens by aromatase
  • estradiol and estrone are the primary secretory products of the ovary
  • estradiol and estrone are converted to estriol in the liver
  • estriol is usually only found in significant amounts in the blood in pregnant women
  • All 3 are produced by the placenta

Question 3

Describe what happens during female puberty:

Answer 3

• GnRH pulses commence at about 9 years of age
  
  • leads to an increase in FSH and then LH
• These restart ovarian follicular development and the production of estradiol
• Increase in estrogen leads to:
  
  • growth spurt
  • development of the secondary sex characteristics
    
    • breast development and pubic hair
• Onset of menstrual cycles is usually the last occurrence during puberty
• Estrogen induces the closure of the growth plates in long bones and leads to an end to the growth spurt

Question 4

Explain what is happening here:

Yes, this is a very long card :-/

Answer 4

1. If pregnancy does not ensue and hCG is not released by the trophoblast into maternal blood, the corpus luteum dies and progesterone and estrogen decrease
2. This loss of negative feedback leads to an increase in FSH (and a small increase in LH)
3. The increase in FSH induces maturation of the next group of follicles
4. A dominant follicle forms (at about 4 days) and begins to release estrogen autonomously
5. The increase in estrogen decreases FSH (and LH) via negative feedback
6. The decrease in FSH leads to atresia of the non-dominant follicles
7. As the dominant follicle grows, it produces more and more estrogen
8. When estrogen peaks, it induces a switch in the hypothalamic-pituitary unit (at least in part due to kisspeptin release in the hypothalamus) from negative to positive feedback so that estrogen stimulates a surge in LH (and to a lesser degree FSH)
   
   • ovaries also produce a hormone called inhibin that preferentially inhibits FSH which is partly the reason why the FSH surge is not as large as the LH surge
9. The LH surge stimulates ovulation and the formation of the corpus luteum
10. The corpus luteum produces enormous amounts of progesterone and to a lesser degree estrogen, both of which inhibit LH and FSH secretion
11. Go back to 1

Question 5

Mechanism of the generation of the positive feedback-induced LH surge:

1. Early follicular phase
2. Middle follicular phase
3. Late follicular phase

Answer 5

1. Early follicular phase
   
   • Dominant follicle produces estrogen that acts LOCALLY
     
     • to stimulate the induction of FSH receptors on granulosa cells (local positive feedback)
   • Allows the follicle to survive the decrease in FSH that occurs in this phase
2. Middle follicular phase:
   
   • Local estrogen positive feedback induces:
     
     • more FSH as well as LH receptors on granulosa cells
     • proliferation of granulosa cells
3. Late follicular phase:
   
   • Estrogen peaks
   • Local estrogen positive feedback has induced a large number of granulosa cells
   • Large increase in estrogen in the blood has induced positive feedback stimulation of LH and FSH → LH surge

Question 6

Describe the interaction of follicular theca and granulosa cells for production of estrogens:

Answer 6

• theca cells
  
  • under the control of LH
  • produce androgens that diffuse into the granulosa cells
• In mature follicles,
  
  • FSH acts on granulosa cells to stimulate aromatase activity
  • converts the androgens to estrogens

Question 7

Describe the Myometrial Cycle:

(Proliferative, Secretory and Luteal Phases)

Answer 7

• Proliferative phase occurs during the follicular phase
  
  • growth of the myometrium stimulated primarily by estrogens
• Secretory phase occurs during the luteal phase due to progesterone (primarily) from the corpus luteum
• Uterine spiral artery vasoconstriction is signaled by the decline of progesterone (and estrogen) at the end of the luteal phase
  
  • leads to sloughing of the myometrium and the menstrual bleed

Question 8

Describe how the corpeus luteum is “rescued”:

Answer 8

• LH peak is arbitrarily set at day 0
• After ovulation, fertilization occurs (usually in the fallopian tube) if sperm are present and functional
• As soon as fertilization occurs, development occurs as the fertilized egg moves down the fallopian tube
• Blastocyst enters the uterine cavity occurs at about 5 days after the LH peak
  
  • about 4 days after fertilization
• Implantation usually occurs at about 7 days
• Once a connection is made between the trophoblasts from the conceptus and the maternal blood, hCG from the trophoblasts is secreting into maternal blood and “rescues” the corpus luteum (which would otherwise regress)

Question 9

Describe how the corpeus luteum is “rescued” by hCG:

Answer 9

hCG stimulates estrogen and progesterone release from the corpus luteum of pregnancy which:

• inhibits gonatropin secretion preventing menstrual cycles during pregnancy
• stimulates continued growth of the endometrium to nurture the growing implanted embryo and fetus

Question 10

What are the steps of trophoblastic steroidogenesis?

Answer 10

1. LDL (low-density lipoprotein) – a source of cholesterol - is taken up
2. Cholesterol is converted to pregnenolone in the mitochondria
3. Pregnenolone passes into the fetus where it can be taken up by the fetal adrenal and processed to adrenal steroid end-products
4. Pregnenolone is converted to progesterone in the SER and progesterone is secreted into the maternal circulation

Question 11

Describe placental steroidogenesis:

Answer 11

Placenta has a lot of aromatase

1. Maternal adrenal testosterone is converted to estradiol in the trophoblast
2. Fetal adrenal (using progesterone from the trophoblast) synthesizes DHEA and then sulfates it (sulfatase enzyme)
3. DHEA from the maternal adrenal and DHEAS from the fetal adrenal cortex is converted to estrone in the placenta
4. Fetal DHEAS is converted to 16OH-DHEAS in the fetal liver.
   
   • 16OH-DHEAS is converted to estriol in the placenta.
   • THEREFORE, measurement of estriol in maternal blood can be used as an index of fetal distress as it assesses fetal adrenal and hepatic function (as well as placental health)

Question 12

• ___ peaks in the first trimester of pregnancy.
• The _______ is responsible for most of the estrogen and progesterone in the 2nd and 3rd trimesters
  
  • What is the consequence of this?
• Describe how placental steroidogenesis is regulated by hCG:

Answer 12

• hCG peaks in the first trimester of pregnancy.
• The placenta is responsible for most of the estrogen and progesterone in the 2nd and 3rd trimesters
  
  • corpus luteum is no longer necessary and hCG wanes
• Placental steroidogenesis uses maternal and fetal androgens as substrate so it is not regulated by hCG

Question 13

Anterior Pituitary during pregnancy:

• GH and ACTH levels
• LH and FSH levels
• PRL levels
• TSH levels

Answer 13

• GH and ACTH secretion are unchanged
• LH and FSH levels are low because of negative feedback of estrogen and progesterone
  
  • corpus luteum in the 1st trimester
  • placenta in the 2nd and 3rd trimesters
• PRL increases steadily throughout gestation preparing the mammary glands for lactogenesis and lactation
• The early increase in TSH stimulates the maternal thyroid:
  
  • thyroid hormone crosses the placenta and is involved in early fetal development
  • TSH is essentially the same as before pregnancy despite the fact that total T4 is increased due to increased TBG

Question 14

Placental Proteins during pregnancy:

• hPL
• CRH burst

Answer 14

• hPL has homology to GH, it is thought to contribute to the insulin-resistant state that occurs in pregnancy
• burst in CRH at the end of pregnancy is hypothesized to contribute to the onset of parturition (not firmly established)

Question 15

Androgens and Estrogens during pregnancy:

Answer 15

huge increase in maternal testosterone

Question 16

Thyroid hormones during pregnancy:

Answer 16

• Total hormone increases because binding proteins increase
• However, free T4 and free T3 do NOT change because they are regulated by negative feedback on the pituitary thyrotrophs.
• In the steady state,
  
  • plasma TSH, Free T4, and Free T3 are the same as before pregnancy.
• Of course, this is only in euthyroid women
  
  • Hyperthyroidism and hypothyroidism can occur during pregnancy

Question 17

Changes During Pregnancy:

• Cardiovascular
• Pulmonary

Answer 17

• Cardiovascular
  
  • CO increase to perfuse the growing placenta.
    
    • HR and SV both increase
  • Placenta is a parallel circulation. Adding it decreases TPR
    
    • remember 1/R = 1/R1 + 1/R2 + 1/Rn for parallel resistances
• Pulmonary
  
  • Increase in minute ventilation to enable increased O₂ consumption
    and CO₂ production by the fetus.
  • In fact, not only do pregnant women display hyperpnea, they occasionally hyperventilate
  • high progesterone is thought to stimulate alveolar ventilation more than the increase in oxygen demand and CO₂ production

Question 18

Changes During Pregnancy:

• Blood
• GI

Answer 18

• Blood volume increases to support the large increase in CO
  
  • In a healthy pregnancy, most plasma electrolytes do not change significantly.
  • Hematocrit decreases slightly because the increase in plasma volume is larger than the increase in red cell mass (erythropoiesis)
• GI: Ask Dr. Franco

Question 19

Changes in Pregnancy:

• Kidney
• Weight

Answer 19

• Kidney:
  
  • Large increase in renal blood flow makes sense to process the increased plasma flow and increased metabolites from increase in metabolic rate
  • GFR is maintained
• Weight:
  
  • Uterus obviously grows very large to accommodate the growing fetus
  • Ideal increase in body weight is not exact, but most feel that a 10-15 kg increase is appropriate
  • Women with hyperemesis gravidarum can lose weight which can be quite dangerous, particularly if it is persistent

Question 20

Vaginal delivery is under ________ feedback control

Answer 20

Vaginal delivery is under positive feedback control

Question 21

Describe the positive feedback of oxytocin:

Answer 21

• As the fetus’ head presses on the cervix,
  
  • afferent nerves carry impulses to the magnocellular nerves in the hypothalamus
  • oxytocin is released the posterior pituitary
• Oxytocin stimulates uterine contractions that increase cervical stretch
• After delivery of the placenta,
  
  • estrogen decreases dramatically which releases the mammary glands to respond to oxytocin
    
    • hypertrophied due to prolactin that has increased through pregnancy
• Suckling stimulates nerve endings in the nipples that follow similar pathways to increase oxytocin release;
  
  • stimulates the myoepithelial cells in the mammary glands to let down milk

Question 22

What happens to the rates of secretion of estrogens, progesterone, and prolactin?

• 8 weeks before parturition
• 36 weeks thereafter

Answer 22

• decrease of prolactin secretion back to basal levels within a few weeks after parturition,
  
  • intermittent periods of marked prolactin secretion (for about 1 hour at a time) during
  • after periods of nursing
• menstrual cycles can resume while nursing continues,
  
  • although the bursts of prolactin do inhibit gonadotropin release

Question 23

• How long is estrogen produced in the body?
• Why is there a decrease in estrogen at menopause?

Answer 23

• Estrogen secretion throughout the life of the female human being
• Decrease in estrogen at menopause is because of the inability of the ovaries to produce mature follicles

Question 24

Describe what happens to gonadotropic hormones during menopause:

Answer 24

• abrupt increase in gonadotropic hormones at menopause in the female
• loss of ovarian steroids releases the hypothalamic-pituitary unit from negative feedback
  
  • ​leading to a large increase in gonadotropin secretion in post-menopausal women

Question 25

What events/disorders lead to decreased estrogen/testosterone and ultimately osteoporosis?

Answer 25

• Females
  
  1. Premenopausal Oophorectomy
  2. Gonadal Dysgenesis (Turner’s)
  3. Premature Ovarian Failure
  4. Hyperprolactinemia
  5. Exercise-Associated Amenorrhea
  6. Menopause
• Males
  
  1. Hypogonadism
  2. Advanced Age