Hormone Action

Question 1

The major hormones of the menstrual cycle are the

Answer 1

ovarian steroids estrogen and progesterone, and the pituitary gonadotropins FSH and LH.

Question 2

Each of these hormones has discrete actions upon a variety of

Answer 2

tissues that ultimately lead to the menstrual cycle.

Question 3

It is important to remember that hormones never act alone; the action of most hormones is modulated by other hormones. For instance, both estrogen and progesterone stimulate

Answer 3

the endometrium to produce the hormone prostaglandin F2 alpha.

Question 4

However, stimulation is only attained if the endometrium is exposed to

Answer 4

estrogen and progesterone in a sequential fashion.

Question 5

For years androgens were considered as detrimental to follicle development mostly due to the association of anovulation and poor oocyte quality with elevated androgen levels in polycystic ovary patients. However, various androgens, including testosterone, androstenedione and dihydrotestosterone (DHT the highly active form of testosterone) have been shown to stimulate

Answer 5

growth and development of mammalian ovarian follicles.

Question 6

It is now recognized that follicle development is positively impacted by the effects of

Answer 6

androgens during the early and intermediate stages of follicular maturation.

Question 7

Androgens produced by the thecal cells of developing follicles facilitate

Answer 7

the transcription of genes involved in the control of primordial follicle recruitment and activation and of genes involved in the promotion of subsequent follicle development.

Question 8

The effects of androgens peak at

Answer 8

the pre-antral and antral stages of follicle development.

Question 9

Androgens primarily act on granulosa cells (GC) via the androgen receptor (AR) and enhance

Answer 9

FSH-driven GC differentiation and thus follicle development. AR expression peaks in GC at the pre-antral and antral stages of follicle development that are also particularly FSH-dependent.

Question 10

The drop in AR expression in mature follicles reduces the action of androgens and thus

Answer 10

FSH-stimulated cell proliferation and differentiation and has been postulated as having a role in the processes of follicular selection and atresia.

Question 11

Effective androgen action on follicle development appears to be limited to a therapeutic range outside of which,

Answer 11

like other hormones, their actions become detrimental.

Question 12

17B-estradiol (E2) is secreted by

Answer 12

the GC of developing follicles.

Question 13

There are two other estrogens besides E2:

Answer 13

1. Estrone (E1)
2. Estriol (E3)

Question 14

E1 is produced by

Answer 14

the ovary and adipose tissue.

Question 15

E3 is produced by

Answer 15

the placenta during pregnancy.

Question 16

At puberty E2 stimulates the

Answer 16

final development and the subsequent maintenance of the reproductive tract.

Question 17

In response to the increase in circulating estradiol at puberty,

Answer 17

the oviduct will enlarge and develop ciliated epithelium and the uterus will increase in size threefold, primarily from myometrium growth.

Question 18

E2 also establishes the female secondary sex characteristics. It is responsible for adult female

Answer 18

breast development, widening of the pelvis long bone growth during puberty and then epiphyseal fusion to terminate bone growth.

Question 19

Menarche is the occurrence of

Answer 19

a first menstrual period in the female adolescent.

Question 20

The onset of pulsatile hypothalamic production of GnRH at puberty stimulates

Answer 20

the pituitary to produce FSH and LH that, in turn stimulate an increase in ovarian production of estrogens and support of folliculogenesis.

Question 21

Rising estradiol levels have a negative regulatory effect on

Answer 21

GnRH secretion and release of the gonadotropins from the pituitary.

Question 22

However, rather than acting on GnRH neurons directly, it appears that estradiol acts on neurons containing ER-alpha receptors that regulate

Answer 22

the transcription of kiss1 the gene that encodes the peptide kisspeptin.

Question 23

The kisspeptin releasing neuron influences GnRH secretion by

Answer 23

by acting through KISS-1 receptors present on GnRH neurons.

Question 24

Kisspeptin

Answer 24

stimulates GnRH release.

Question 25

During the menstrual cycle E2 acts as a

Answer 25

mitogen on the uterine endometrium by stimulating the proliferation of epithelial cells glands and stroma cells.

Question 26

E2 stimulates a myriad of cytoplasmic enzymes that prepare the endometrium to

Answer 26

become a secretory tissue in response to progesterone and also increases the excitability of the myometrium.

Question 27

Progesterone

Answer 27

Prepares the uterus for pregnancy and when a woman becomes pregnant.

Question 28

The two major hormonal actions associated with progesterone are

Answer 28

1. stimulation of the oviducts and uterus to become secretory 2. Inhibition of myometrial activity

Question 29

Under the influence of progesterone the size (hypertrophy) and number of endometrial glands markedly

Answer 29

increase.

Question 30

Progesterone also changes the metabolic activity of the endometrium with the production of

Answer 30

nutritive substances, especially glycogen, that will be used by the implanted conceptus.

Question 31

A secondary effect of progesterone, related to pregnancy, is

Answer 31

to promote the growth of alveoli and lobules within the breast preparing for lactation.

Question 32

Progesterone also has a generalized stimulatory effect on systemic metabolism. This stimulation is particularly noticeable just after ovulation when it causes

Answer 32

a subtle increase in basal (resting) body temperature (BBT).

Question 33

The elevation of progesterone during the early luteal phase will raise the BBT by

Answer 33

0.3-0.5°C (0.5-1.0°F) and can be used clinically as an indicator of ovulation.

Question 34

Progesterone levels are low during the first part of the follicular phase of the menstrual cycle and start to rise

Answer 34

approximately 48 hours prior to the initiation of the LH surge.

Question 35

Granulosa cells undergoing luteinization

Answer 35

secrete large amounts of progesterone leading to an increase in measurable systemic progesterone levels.

Question 36

These differentiating GC express the progesterone receptor suggesting a role for progesterone in

Answer 36

ovulation and luteinization.

Question 37

A premature increase in progesterone levels can induce changes to follicular and endometrial cell function potentially impacting

Answer 37

oocyte quality and/or endometrial receptivity.

Question 38

FSH is responsible for stimulation of

Answer 38

granulosa cells.

Question 39

Pituitary FSH binds to FSH membrane receptors (FSHR) on the GC of the follicle and stimulates

Answer 39

pre-ovulatory follicle growth and estradiol production by triggering cytodifferentiation and proliferation of the GC.

Question 40

FSH also stimulates several steroidogenic enzymes including

Answer 40

aromatase and 38-HSD.

Question 41

FSHR expression on target cells is essential for

Answer 41

modulation of ovarian function by FSH and is required in mature follicles to avoid death by atresia.

Question 42

FSH levels begin to rise during the last few days of the preceding menstrual cycle due to

Answer 42

declining steroid production by the CL and a dramatic fall in inhibin A levels.

Question 43

Low sex steroid levels release the negative feedback on GnRH pulsatile secretion that leads to

Answer 43

an elevation of FSH secretion.

Question 44

Elevated FSH levels recruit and support (cyclic recruitment) the development of

Answer 44

a cohort of follicles in each ovary, one of which is destined to ovulate during the upcoming menstrual cycle.

Question 45

Once menses ensues, FSH levels begin to decline due to the negative feedback of rising

Answer 45

estrogen levels and the negative effects of inhibin B produced by the GC of the developing follicle.

Question 46

FSH levels surge mid-cycle, like LH levels, but

Answer 46

the increase is tempered by the negative regulatory effect of inhibin B.

Question 47

FSH levels early in the menstrual cycle have been used for many years as a biomarker

Answer 47

of ovarian reserve.

Question 48

The blood test assessed both FSH and estradiol levels and is preferably performed on cycle

Answer 48

day 3 when estradiol levels, that affect FSH levels via negative feedback control, are generally low.

Question 49

Pituitary LH binds to LH membrane receptors (LHR) on

Answer 49

the thecal cells and stimulates androgen production.

Question 50

These androgens produced by the theca cells are metabolized by

Answer 50

the GC to produce estradiol (two cell theory)

Question 51

LH levels increase slowly throughout the follicular phase of the menstrual cycle. Mid-cycle a surge of LH secretion is triggered by

Answer 51

a dramatic rise of estradiol produced by the preovulatory follicle.

Question 52

The dominant follicle is almost always more than 15 mm in diameter to

Answer 52

produce the critical concentration of estradiol needed to initiate the positive neuroendocrine feedback on the anterior pituitary.

Question 53

FSH and LH bind to their G-protein coupled receptors FSHR and LHCGR (LHR) respectively bringing about

Answer 53

the activation of adenyl cyclase, inactivation of intracellular cAMP, and a decline in protein kinase A (PKA) levels.

Question 54

This in turn releases the block on

Answer 54

meiotic progression.

Question 55

It is also recognized that signaling events controlled by the gonadotropins in ovarian GCs also involve many additional signaling molecules, including

Answer 55

SRC tyrosine kinase, RAS, protein kinase B (PKB/AKT), and mitogen-activated protein kinases (MAPKS) .

Question 56

However, thed LHR is expressed predominantly by thecal and mural granulosa cells and thus paracrine signaling and intercellular communications must be essential for

Answer 56

cumulus-oocyte complex response to the LH surge.

Question 57

The LH surge initiates final maturational changes in the oocyte, ovulation and

Answer 57

stimulates luteinization of the follicle.

Question 58

After the formation of the CL,

Answer 58

LH stimulates luteal progesterone production.

Question 59

GnRH produced by the hypothalamus controls the secretion of the gonadotropins

Answer 59

LH and FSH.

Question 60

The cell bodies of the GnRH neurons are located in

Answer 60

the preoptic nucleus of the brain.

Question 61

These neurons fire in an episodic fashion that, in turn,

Answer 61

elicits a pulsatile pattern of gonadotropin release.

Question 62

The responsiveness of the pituitary to GnRH is dependent upon the

Answer 62

frequency and duration of the GnRH pulses.

Question 63

Slow GnRH plasticity favors

Answer 63

FSH secretion.

Question 64

Fast pulse frequencies support

Answer 64

LH secretion.

Question 65

The release of GnRH in a pulsatile manner is essential for stimulation of

Answer 65

the gonadotropin secreting cells in the anterior pituitary. Failure of this mechanism renders the pituitary unresponsive.