Female Hormones

Question 1

What are the main functions of the ovaries?

Answer 1

-Oogenesis, or the production of female gametes during the fetal period-Maturation of the oocyte when it is ready for fertilization-ovulation of the mature oocyte-production of the female sex steroid hormones, estrogen and progesterone, and the peptide hormones inhibin and activin

Question 2

Give an overview of the products of oogenesis

Answer 2

Oogenesis begins duringembryonic development asdiploidoogonia (46,2N)that undergo many mitoses so thatfemales are typically born with 2-4 million diploidprimary oocytes (46, 4N)(no new oocytes are procued after birth). These primary oocytes are arrested in prophase of meiosis I (and99.99% of which undergo degeneration) until ovulation occurs and meiosis I completes to produce haploidsecondary oocytes (23, 2N), which again arrest in metaphase. Meiosis II is completed at fertilization (or the 2ndary ooccytes degenerate) to produce an haploidovum (23, N)

Question 3

When does the follicular phase of human oocyte maturation occur?

Answer 3

Days 1-14 of a typical cycle (this part can vary in length but the luteal phase is fixed at 14 days)

Question 4

What are the developmental stages of the follicular phase of human oocyte maturation?

Answer 4

1. Primordial follicle2. Primary follicle3. Preantral/early antral follicles4. Mature follicle (1st Meiosis completes)

Question 5

What is the role of theca cells during oocyte maturation?

Answer 5

providing signal transduction betweengranulosa cellsandoocytesduring development by the establishment of a vascular system, providing nutrients, and providing structure and support to the follicle as it matures.The theca cells are also responsible for the production ofandrostenedione, and indirectly the production of 17βestradiol, also called E2, by supplying the neighboringgranulosa cellswithandrostenedionethat with the help of the enzymearomatasecan be used as a substrate for this type ofestradiol. FSH induces the granulosa cells to make aromatase that converts the androgens made by the theca interna into estradiol.

Question 6

What is the role of granulosa cells during oocyte maturation?

Answer 6

These are the cells directly lining the ovarian follicle and have a primary function of hormone production (estrogen, progesterone, inhibin, and activin)These proliferate with oocyte maturation

Question 7

What happens on Day 14 of the menstrual cycle?

Answer 7

Ovulation- amature secondary oocyte (23,2N) is released from the follicle to the ovarian surface as meiosis I is completed

Question 8

What occurs during days 14-25 of the menstrual cycle?

Answer 8

The luteal phase, which occurs post-ovulation, and is marked by the formation of the corpus luteum (which regresses after 10 days- days 25-28- if no fertilization occurs)

Question 9

What hormones does the corpus luteum secrete?

Answer 9

progesterone!! (the elevation of progesterone is indicative of ovulation), and some estrogen,inhibin, and activin

Question 10

What is the main source of the cholesterol needed to make steroid hormones?

Answer 10

LDL from the liver

Question 11

What are the female sex steroid hormones?

Answer 11

-Estrogens (17B-estradiol (E2), Estrone (E1), and Estriol (E3))-Progesterone

Question 12

What are estrone and estriol?

Answer 12

Estrone is a weak estrogen and a precursor of E2, while Estriol (E3)is even weaker than E1 and is a metabolite of E2.17B-Estradiol is the major estrogen in the body

Question 13

What organs make 17B-Estradiol?

Answer 13

Ovaries (directly produce 17B-estradiol),Adrenal glands, placenta,adipose tissue (contains aromatase to convert testosterone and androstenedione)

Question 14

What cells in the ovaries produce progesterone?

Answer 14

-theca cells-corpus luteum (after ovulation)

Question 15

When do theca cells produce progesterone?

Answer 15

during the follicular phase and up to ovulation

Question 16

When doesthe corpus luteum produce progesterone?

Answer 16

This is the main source of progesterone-post-ovulation

Question 17

How is progesterone produced in the ovary theca cells?

Answer 17

LH from the anterior pituitary stimulates cholesterol desmolase (CYP11A1) stored in the mitcohondria of the theca cells to produce pregnenolone from cholesterol, which is then transformed to progesterone via 3B-HSD.NOTE: LH also inhibits 17a-hydroxylase (inhibits conversion of pregnenolone to 17-hydroxypregnenlone)at high levels to shut down production of testosterone and 17B-estradiol

Question 18

How is 17B-Estradiol made (1 of 2)?

Answer 18

1) Cholesterol is converted to pregnenolone via cholesterol desmolase via LH infuence2) Pregnenolone is converted to 17-Hydroxypregnenolone via 17a-hydroxylase3) 17-Hydroxypregnenolone is converted to DHEA via 17,20-lyase4) DHEA is converted to Androstenedione via 3B-HSDAll in the theca cells

Question 19

What things can happen to androstenedione?

Answer 19

It can be converted to testosterone by diffusing into granulosa cells and via 17B-HSD orit can be converted to estrone in the theca cells via aromatase

Question 20

How istestosterone converted to 17B-estradiol in the ovaries?

Answer 20

Via aromatase under positive influence of FSH from the anterior pituitary

Question 21

Estrogen production is age-dependent. Give a brief outline of the levels of estrogen in the body at various points in life.

Answer 21

Estrogen production starts at an early embryonic age (8-12 weeks) and is thought to be very important in the development of internal female organs. By birth estrogen levels fall significantly until about 2-3 mo of age when a transient “minipuberty” occurs which is thought to stimulate brain development. Levels then drop again to near zero until puberty, where they remain high until about 45 yers of age, which sees a progressive decreased in estrogen secretion by the ovaries and a small compensation by the adipose tissues

Question 22

Describe the Hypothalamic-Pituitary-Gonadal Axis

Answer 22

The Hypothalamus produces pulsatileGnRH which promotes secretion of LH and FSH from the anterior pituitary to act on the ovaries to produce testosterone, estrogen, progesterone, activin, and inhibin

Question 23

Describe what is happening in this graph

Answer 23

During childhood, levels of FSH and LH are very low until puberty which is met with a 5-10x increase in the gonadotropins. During menopause, the decreased producton of estrogen produces a lack of negative feedback on the production of FSH and LH and their levels surge up to 10x where they remain high into the 60s until slowly decreasing until death

Question 24

How do the LOW levels of estradiol affect production of FSH, LH, and GnRH during the early and middle follicular phase of ovulation?

Answer 24

Low levels of estradiol inhibit production of GnRH and mainly LH from the anterior pituitary, whereas inhibin production during this phase from the ovaries inhibits FSH

Question 25

What occurs immeditealy prior to ovulation?

Answer 25

Estradiol production from the ovaries increases causing a positive feedback on production of GnRH from the hypothalamus and up-regulation of GnRH receptors and increased LH (mainly) and FSH production in the anterior pituitary. LH increases causes the ovulatory surge and induces ovulation of the mature oocyte and formation of the corpus luteum

Question 26

What happens to the levels of GnRH, LH, and FSH during the luteal phase?

Answer 26

Progesterone begins to be produced in higher quantities from the corpus luteum which has a negative feedback on both GnRH and LH and inhibin from the ovaries inhibits the production of FSH

Question 27

How does estrogen circulate in the body?

Answer 27

98% bound

Question 28

What are the main carriers of estrogen in the blood?

Answer 28

high affinity specific binding (45-70%): Beta globulins like sex steroid-binding globulin (SSBG) andlow affinity binding (30-50%): Albumin

Question 29

How does estrogen act in the long-term?

Answer 29

Estrogen is membrane permeable and diffuses into the cytoplasm where it binds to nuclear receptors ERa and ERb which transport it to the nucleus to initiate RNA transcription

Question 30

What are the fast responses of estrogen mediated by?

Answer 30

There are receptors, both membrane-bound and cytosolic, that bind estrogen and mediate secondary messenger cascades

Question 31

How does estrogen affect bone?

Answer 31

Preserves bone density (upregulates osteroprotegerin)

Question 32

How does estrogen affect cholesterol levels?

Answer 32

decreases LDL cholesterol but increases HDL

Question 33

How does estrogen affect the heart?

Answer 33

It is cardioprotective-Estrogen is believed to have a positive effect on the inner layer of arterial intima, helping to keep blood vessels flexible. That means they can relax and expand to accommodate blood flow.

Question 34

How does estrogen affect blood vessels?

Answer 34

It has anti-atherosclerotic effects and reduces plaque formation

Question 35

How does estrogen affect the brain?

Answer 35

Estrogen helps to maintain body temp, may delay memory loss, and helps the brain prepare for sexual development

Question 36

What are the effects of estrogen on the breast, uterus, ovaries, and vagina?

Answer 36

Estrogen stimulates maturation of all of these

Question 37

How does progesterone affect the uterus?

Answer 37

It prepares the uterus for implantation of the fertilized ovum and pregnancy during the luteal phase by stimulating endometrial glandular secretions and spiral artery development-produces thick cervical mucus, which inhibits sperm entry into the uterus-causes uterune smooth muscle relaxation (preventing contractions) and decreases myometrial excitability

Question 38

The best time for fertilization is within 12-24 hrs of ovulation

Question 39

Where are inhibin and activin made?

Answer 39

granulosa cells

Question 40

What are the functions of inhibin?

Answer 40

Negative feedback on FSH secretion to reduce estrogen production

Question 41

What are the functions of activin?

Answer 41

Positive feedback on the anterior pituitary to stimulate FSH secretion resulting in increased estrogen production

Question 42

How does estrogen affect prolactin secretion?

Answer 42

it promotes but blocks its action at the breast

Question 43

What does progesterone do to body temp?

Answer 43

increases it (post-ovulation, body temp is high)

Question 44

How does progesterone affect estrogen receptors?

Answer 44

it down-regulates them