Reproductive Endocrinology

Question 1

Sex steroids are secreted in significant amounts by what three organs?

Answer 1

1. adrenal cortex
2. placenta
3. gonads (testis and ovary)

Question 2

The three major classes of sex steroids differ with respect to the number of carbons they contain. What are they?

Answer 2

pregnanes (21 C)
androgens or androstanes (19 C)
estrogens or estranes (18 C).

Question 3

Which cannot be converted to estrogen, testosterone or dihydrotestosterone?

Answer 3

dihydrotestosterone (DHT)

Question 4

The primary male hormone is testosterone (T) which is an ___. T is more potent than ___ and ___. T is converted to the most potent androgen, ___, by the enzyme ___-___.

Answer 4

androgen; DHEA; androstenedione; DHT; 5α-reductase

Question 5

The primary female hormones are ___ which is a progestin, and ___ which is an estrogen.

Answer 5

progesterone; estradiol

Question 6

___ can serve a precursor for other steroids.

Estradiol is an estrogen produced from ___ by the enzyme ___.

Answer 6

Progesterone; testosterone; aromatase

Question 7

Can steroids be stored?

Answer 7

No, because that they are lipophilic hormones, steroids cannot be stored

Question 8

What controls the synthesis and secretion of sex steroids?

Answer 8

the neuroendocrine system; the reproductive or HPG axis includes the hypothalamus, anterior pituitary gland and the gonads.

Question 9

GnRH secretion from the hypothalamus is ___ due to the activity of pacemaker neurons that spontaneously produce action potentials resulting in secretory bursts of GnRH.

Answer 9

pulsatile

Question 10

T/F. Secretion of the gonadotropic hormones luteinizing hormone (LH) and follicle stimulating hormone (FSH) from the anterior pituitary is pulsatile in response to bursts of GnRH from the hypothalamus. Pulsatile secretion of LH and FSH stimulates pulsatile secretion of gonadal steroids.

Answer 10

True.

Question 11

What does continuous, nonpulsatile GnRH stimulation cause?

Answer 11

Continuous, nonpulsatile GnRH downregulates GnRH receptors in the anterior pituitary and inhibits LH and FSH secretion.

Question 12

Most of the time the gonadal steroids exert negative feedback control of GnRH and LH secretion, what is the exception?

Answer 12

E2 has positive feedback actions on LH secretion prior to ovulation.

Question 13

Activation of steroid receptors regulates gene ___. In the gonads, the genes transcribed are those regulating ___ and ___ hormone synthesis.

Answer 13

transcription; gametogenesis; steroid

Question 14

T/F. Gonadal steroids also regulate protein synthesis in other reproductive organs including male accessory glands, the uterus, breasts, and the brain.

Answer 14

True.

Question 15

What are the three important cells in the testis with important reproductive functions?

Answer 15

1. Spermatic cells (gametes)
2. Leydig or interstitial cells
3. Sertoli cells

Question 16

Spermatic cells (gametes) include ___ active spermatogonia and ___ spermatocytes.

Answer 16

mitotically; meiotic

Question 17

Spermatogenesis proceeds as the spermatic cells move through the wall of the ___ ___ from the ___ ___ towards the ___ surface and ___.

Answer 17

seminiferous tubules; basal lamina; apical; lumen

Question 18

Where do Leydig cells lie?

Answer 18

outside of the seminiferous tubules

Question 19

Which cells synthesize T? What makes them do that?

Answer 19

Leydig cells synthesize T in response to LH

Question 20

In the brain, T regulates ___ ___ (after being aromatized to ___). Elsewhere
in the body T regulates ___ ___ characteristics.

Answer 20

sexual behavior; E2; secondary sex

Question 21

What are the epithelial cells that line the seminiferous tubules?

Answer 21

Sertoli cells or sustentacular cells

Question 22

In response to FSH, ___ cells regulate spermatogenesis and produce the peptide hormone ___, which has negative feedback on ___ secretion.

Answer 22

Sertoli; inhibin; FSH

Question 23

In addition to inhibin, what else does Sertoli cells produce?

Answer 23

Sertoli cells also produce an androgen binding protein that helps sequester T in the testis so spermatogenesis is continuous. The Sertoli cells also secrete tubular fluid to provide nutrient support for spermatozoa.

Question 24

Why is it important that Sertoli cells sequester T?

Answer 24

By sequestering T, Sertoli cells can undergo spermatogenesis continuously. This is key because GnRH is released in a pulsaltile fashion and we want spermatogenesis to continue without interruption.

Question 25

Why is male birth control that inhibits T not used?

Answer 25

It inhibits spermatogenesis AND secondary sex characteristics

Question 26

What happens if birthcontrol released excess inhibin?

Answer 26

this would shut off FSH secretion so spermatogenesis could not be stimulated in Sertoli cells, BUT this is not absolute and some sperm are still produced. Also, it is a peptide hormone that would be digested in the intestines and therefore, cannot be given orally.

Question 27

Both DHT and T bind the same receptor but DHT is more potent. Why?

Answer 27

DHT binds the receptor with a higher affinity

Question 28

T is converted to ___ or ___ which later converts to estrone by ___ in the brain and bone.

Answer 28

estradiol; androstenedione; aromatase

Question 29

What are aromatase inhibitors used to treat?

Answer 29

breast and prostate cancers because many tumors are estrogen sensitive

Question 30

What is used to treat hair loss?

Answer 30

5α-reductase inhibitors used to treat hair loss because DHT promotes hair loss in male pattern baldness

Question 31

T/F. Within the reproductive system, T is important for sexual differentiation, development and maintenance of secondary sex characteristics, libido, and sexual behavior. What other effects of T are important in females?

Answer 31

True, but the last two (libido and sexual behavior) need to be converted to E. regulate bone growth stimulate muscle growth (b/c T is an anabolic steroid) stimulate erythropoiesis (T is cofactor, therefore men can produce more RBCs)

Question 32

Desscribe andropause.

Answer 32

andropause is characterized by an increase in emotional disorders associated with aging. no obvious decline in reproductive function although testosterone production does decrease with age. most men remain fertile despite decreased sperm counts and motility. not clear if T decline is associated with emotional problems

Question 33

What are the four ovarian cells that are important for reproduction functions?

Answer 33

1. oocytes 2. theca cells 3. granulosa cells 4. luteal cells

Question 34

What is each oocyte enclosed in? What phase are they arrested in?

Answer 34

each oocyte is enclosed within a ball of cells called an ovarian follicle. Note that there are no oogonia. Shortly after birth, all oocytes are arrested in prophase of meiosis I.

Question 35

What cells surround each follicle and have a location and function similar to that of Leydig cells?

Answer 35

Theca cells

Question 36

What cells are the epithelial cells of the follicle and analogous to Sertoli cells?

Answer 36

Granulosa cells

Question 37

In an early follicle, ___ or more layers of cells surround the oocyte. Large, developing follicles become filled with ___, and the granulosa cells continue to surround the oocyte in the ___ ___.

Answer 37

one; fluid; cumulus oophorus

Question 38

___ cells are present after ovulation when the theca and granulosa cells from the ovulatory follicle are transformed into the cells of the ___ ___.

Answer 38

Luteal; corpus luteum

Question 39

___ cells synthesize ___ in response to LH, which diffuses into ___ cells or into the systemic circulation (blood).

Answer 39

Theca; androstenedione; granulosa

Question 40

In response to FSH, what two things do granulosa cells do?

Answer 40

1. convert androstenedione to estrone which is converted to estradiol (E2) 2. secrete inhibin that has a negative feedback effect on FSH secretion

Question 41

Estradiol (E2) stimulates ___ cell function and replication, regulates ___ development, regulates female ___ sex characteristics, important regulator of ___ turnover and ___ function, typically inhibits ___ and ___ secretion.

Answer 41

granulosa; oocyte; secondary; bone; arterial; GnRH; LH

Question 42

T/F. larger follicles are going to have more LH and FSH receptors, and will produce greater amounts of both E2 and inhibin.

Answer 42

True.

Question 43

List the steps in order of the ovarian cycle. 1. meiosis I completed, ovulation, CL formation 2. : increase E2 and inhibin; dominant follicle selection 3. FSH decrease, E2 peak, LH surge (positive feedback action of E2 on GnRH and LH) 4. gonadotropin rise and follicular development 5. increase E2 and P, inhibit gonadotropins 6. CL regression, decrease steroids, gonadotropins rise

Answer 43

4, 2, 3, 1, 5, 6

Question 44

When does the menstrual phase begin?

Answer 44

When the CL regresses and steroid support for uterine endometrium is lost

Question 45

During which phase, menstrual or proliferative, does follicular E2 stimulate proliferation of the endometrium?

Answer 45

proliferative phase

Question 46

During the ___ phase, P and E2 stimulate uterine secretory activity; increase glandular production of ___, increase ___, decrease ___.

Answer 46

luteal; glycogen; angiogenesis; contractility

Question 47

What happens once the corpus luteum regresses?

Answer 47

the menstrual phase starts again

Question 48

If pregnancy occurs, what produces human chorionic gonadotropin (hCG)? What is the function of hCG?

Answer 48

placenta hCG is similar to LH and maintains luteal steroidogenesis until the placenta develops fully

Question 49

What is the cessation of the menstrual cycles that is primarily due to ovarian failure? Why does this occur?

Answer 49

Menopause There is loss of the ovarian follicle due to atresia

Question 50

What are the hormonal consequences to menopause?

Answer 50

lose ovarian steroids gonadotropin secretion very high increase reliance on adrenal steroids

Question 51

Differentiation of gonadal sex is determined by the presence of a gene on the Y chromosome that encodes for ___ protein.

Answer 51

SRY

Question 52

What is the role of the SRY gene?

Answer 52

it directs the indifferent gonad to become a testis

Question 53

What two hormones are produced by the fetal testis that regulate sexual differentiation of the INTERNAL genitalia?

Answer 53

T and Mullerian inhibiting substance (MIS)

Question 54

In the undifferentiated state, there are two sets of tubules associated with the developing gonad, what are they called?

Answer 54

the Wolffian ducts and the Müllerian ducts

Question 55

T/F. In a developing male, MIS stimulates proliferation of the Wolffian duct system that will become the tubules associated with the male reproductive tract. T causes the Müllerian duct system to regress.

Answer 55

False, In a developing male, T stimulates proliferation of the Wolffian duct system that will become the tubules associated with the male reproductive tract. MIS causes the Müllerian duct system to regress.

Question 56

T/F. In the developing female there is NO significant production of gonadal steroids.

Answer 56

True.

Question 57

What does the absence of T do in the developing female?

Answer 57

causes regression of the Wolffian duct system

Question 58

What does the absence of MIS do in the developing female?

Answer 58

It results in proliferation or maintenance of the Müllerian duct system that becomes the tubules of the female reproductive tract.

Question 59

The early embryo and fetus are undifferentiated up to ~___ weeks of gestation.

Answer 59

9

Question 60

What is three structures are found in both the male and female external genitalia?

Answer 60

a genital tubercle, urogenital fold, and labioscrotal fold/genital folding.

Question 61

Androgens from the developing ___ (mostly T converted peripherally to DHT) stimulate differentiation of male external genitalia. What happens in females?

Answer 61

testes The absence helps females develop their external genitalia

Question 62

What do the following develop into in the male and female? genital tubercle urogenital fold labioscrotal folds

Answer 62

In Male: genital tubercle = glans of penis urogenital fold = urethra and surrounding penis labioscrotal folds = scrotum and skin of penis In Female: genital tubercle = glans of clitoris urogenital fold = labia minor and urethral opening labioscrotal fold = labia majora

Question 63

T/F. The brain is also sexually differentiated due to the effects of T aromatized to E2 in the developing male.

Answer 63

True

Question 64

___ ___ ___ is due to an adrenal enzyme deficiency that results in excess production of adrenal androgens.

Answer 64

Congenital adrenal hyperplasia

Question 65

For example, what happens if the enzyme 21α hydroxylase is mutated?

Answer 65

This will prevent the synthesis of cortisol. The decreased negative feedback of cortisol on ACTH secretion leads to an increase stimulation of adrenal cortex. Therefore, there is an increased production of adrenal androgens.

Question 66

If a female fetus (XX) has been exposed to T, what will happen to her phenotype?

Answer 66

phenotype is virilized or more male than female depending on severity

Question 67

If a female fetus (XX) has been exposed to T, what will happen to her gonads and internal genitalia?

Answer 67

She will have ovaries because the Mullerian duct persist since there is no MIS (because no testis present). She will also retain the Wolffian duct due to the presence of T.

Question 68

What is another name for 5α-reductase deficiency?

Answer 68

guevodoces

Question 69

The development of what structures is dependent on DHT?

Answer 69

penis scrotum prostate gland

Question 70

What happens with 5α-reductase deficiency? What is the genotype for individuals with this deficiency?

Answer 70

The enzyme deficiency results in failure of differentiation of the external genitalia early in life, but increased T secretion with the onset of puberty completes differentiation. Genotype XY

Question 71

What is the phenotype of 5α-reductase deficiency?

Answer 71

female at birth until early puberty

Question 72

What is the effects on the gonads and internal genitalia?

Answer 72

Gonads are testes that produce T, therefore the Wolffian duct is present (it is not DHT dependent). The Mullerian duct regresses because T is present so they can make MIS which causes the regression.

Question 73

What causes Testicular feminization or androgen insensitivity?

Answer 73

lack of lack functional androgen receptor (used by both T and DHT)

Question 74

T/F. There is no differentiation of genitalia in Testicular feminization or androgen insensitivity because there is no functional receptor.

Answer 74

True.

Question 75

If the genotype in Testicular feminization or androgen insensitivity is XY, why is the phenotype female?

Answer 75

Because T has no receptors it is converted into E, which increases breast tissue. This condition is often diagnosed at puberty when there is no menstration

Question 76

What are the effects of the gonads and internal genitalia in Testicular feminization or androgen insensitivity individuals?

Answer 76

The gonads are testis (XY). Although they make T, there is no functional receptor so the Wolffian duct is not present. However, they are still able to make MIS, so the Mullerian duct regresses.

Question 77

There is a dramatic increase in circulating concentrations of steroid hormones during pregnancy due to ___ production.

Answer 77

placental

Question 78

If the corpus luteum regresses after ~3 months, what supports luteal steroidogenesis?

Answer 78

hCG

Question 79

Placental ___ stimulates growth of myometrium and placental ___ reduces uterine contractility and stimulates vasodilation.

Answer 79

E2; P

Question 80

What considerations should be taken for a pregnant dental patient?

Answer 80

They are more susceptible to gingivitis and periodontitis due to elevated steroid hormones medications and x-rays could affect fetus comfort during exam or procedure