Reproductive Endocrinology Flashcards
Sex steroids are secreted in significant amounts by what three organs?
- adrenal cortex
- placenta
- gonads (testis and ovary)
The three major classes of sex steroids differ with respect to the number of carbons they contain. What are they?
pregnanes (21 C)
androgens or androstanes (19 C)
estrogens or estranes (18 C).
Which cannot be converted to estrogen, testosterone or dihydrotestosterone?
dihydrotestosterone (DHT)
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 ___-___.
androgen; DHEA; androstenedione; DHT; 5α-reductase
The primary female hormones are ___ which is a progestin, and ___ which is an estrogen.
progesterone; estradiol
___ can serve a precursor for other steroids.
Estradiol is an estrogen produced from ___ by the enzyme ___.
Progesterone; testosterone; aromatase
Can steroids be stored?
No, because that they are lipophilic hormones, steroids cannot be stored
What controls the synthesis and secretion of sex steroids?
the neuroendocrine system; the reproductive or HPG axis includes the hypothalamus, anterior pituitary gland and the gonads.
GnRH secretion from the hypothalamus is ___ due to the activity of pacemaker neurons that spontaneously produce action potentials resulting in secretory bursts of GnRH.
pulsatile
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.
True.
What does continuous, nonpulsatile GnRH stimulation cause?
Continuous, nonpulsatile GnRH downregulates GnRH receptors in the anterior pituitary and inhibits LH and FSH secretion.
Most of the time the gonadal steroids exert negative feedback control of GnRH and LH secretion, what is the exception?
E2 has positive feedback actions on LH secretion prior to ovulation.
Activation of steroid receptors regulates gene ___. In the gonads, the genes transcribed are those regulating ___ and ___ hormone synthesis.
transcription; gametogenesis; steroid
T/F. Gonadal steroids also regulate protein synthesis in other reproductive organs including male accessory glands, the uterus, breasts, and the brain.
True.
What are the three important cells in the testis with important reproductive functions?
- Spermatic cells (gametes)
- Leydig or interstitial cells
- Sertoli cells
Spermatic cells (gametes) include ___ active spermatogonia and ___ spermatocytes.
mitotically; meiotic
Spermatogenesis proceeds as the spermatic cells move through the wall of the ___ ___ from the ___ ___ towards the ___ surface and ___.
seminiferous tubules; basal lamina; apical; lumen
Where do Leydig cells lie?
outside of the seminiferous tubules
Which cells synthesize T? What makes them do that?
Leydig cells synthesize T in response to LH
In the brain, T regulates ___ ___ (after being aromatized to ___). Elsewhere
in the body T regulates ___ ___ characteristics.
sexual behavior; E2; secondary sex
What are the epithelial cells that line the seminiferous tubules?
Sertoli cells or sustentacular cells
In response to FSH, ___ cells regulate spermatogenesis and produce the peptide hormone ___, which has negative feedback on ___ secretion.
Sertoli; inhibin; FSH
In addition to inhibin, what else does Sertoli cells produce?
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.
Why is it important that Sertoli cells sequester T?
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.
Why is male birth control that inhibits T not used?
It inhibits spermatogenesis AND secondary sex characteristics
What happens if birthcontrol released excess inhibin?
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.
Both DHT and T bind the same receptor but DHT is more potent. Why?
DHT binds the receptor with a higher affinity
T is converted to ___ or ___ which later converts to estrone by ___ in the brain and bone.
estradiol; androstenedione; aromatase
What are aromatase inhibitors used to treat?
breast and prostate cancers because many tumors are estrogen sensitive
What is used to treat hair loss?
5α-reductase inhibitors used to treat hair loss because DHT promotes hair loss in male pattern baldness
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?
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)
Desscribe andropause.
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
What are the four ovarian cells that are important for reproduction functions?
- oocytes
- theca cells
- granulosa cells
- luteal cells
What is each oocyte enclosed in? What phase are they arrested in?
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.
What cells surround each follicle and have a location and function similar to that of Leydig cells?
Theca cells
What cells are the epithelial cells of the follicle and analogous to Sertoli cells?
Granulosa cells
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 ___ ___.
one; fluid; cumulus oophorus
___ cells are present after ovulation when the theca and granulosa cells from the ovulatory follicle are transformed into the cells of the ___ ___.
Luteal; corpus luteum
___ cells synthesize ___ in response to LH, which diffuses into ___ cells or into the systemic circulation (blood).
Theca; androstenedione; granulosa
In response to FSH, what two things do granulosa cells do?
- convert androstenedione to estrone which is converted to estradiol (E2)
- secrete inhibin that has a negative feedback effect on FSH secretion
Estradiol (E2) stimulates ___ cell function and replication, regulates ___ development, regulates female ___ sex characteristics, important regulator of ___ turnover and ___ function, typically inhibits ___ and ___ secretion.
granulosa; oocyte; secondary; bone; arterial; GnRH; LH
T/F. larger follicles are going to have more LH and FSH receptors, and will produce greater amounts of both E2 and inhibin.
True.
List the steps in order of the ovarian cycle.
- meiosis I completed, ovulation, CL formation
- : increase E2 and inhibin; dominant follicle selection
- FSH decrease, E2 peak, LH surge (positive feedback action of E2 on GnRH and LH)
- gonadotropin rise and follicular development
- increase E2 and P, inhibit gonadotropins
- CL regression, decrease steroids, gonadotropins rise
4, 2, 3, 1, 5, 6
When does the menstrual phase begin?
When the CL regresses and steroid support for uterine endometrium is lost
During which phase, menstrual or proliferative, does follicular E2 stimulate proliferation of the endometrium?
proliferative phase
During the ___ phase, P and E2 stimulate uterine secretory activity; increase glandular production of ___, increase ___, decrease ___.
luteal; glycogen; angiogenesis; contractility
What happens once the corpus luteum regresses?
the menstrual phase starts again
If pregnancy occurs, what produces human chorionic gonadotropin (hCG)? What is the function of hCG?
placenta
hCG is similar to LH and maintains luteal steroidogenesis until the placenta develops fully
What is the cessation of the menstrual cycles that is primarily due to ovarian failure? Why does this occur?
Menopause
There is loss of the ovarian follicle due to atresia
What are the hormonal consequences to menopause?
lose ovarian steroids
gonadotropin secretion very high
increase reliance on adrenal steroids
Differentiation of gonadal sex is determined by the presence of a gene on the Y chromosome that encodes for ___ protein.
SRY
What is the role of the SRY gene?
it directs the indifferent gonad to become a testis
What two hormones are produced by the fetal testis that regulate sexual differentiation of the INTERNAL genitalia?
T and Mullerian inhibiting substance (MIS)
In the undifferentiated state, there are two sets of tubules associated with the developing gonad, what are they called?
the Wolffian ducts and the Müllerian ducts
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.
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.
T/F. In the developing female there is NO significant production of gonadal steroids.
True.
What does the absence of T do in the developing female?
causes regression of the Wolffian duct system
What does the absence of MIS do in the developing female?
It results in proliferation or maintenance of the Müllerian duct system that becomes the tubules of the female reproductive tract.
The early embryo and fetus are undifferentiated up to ~___ weeks of gestation.
9
What is three structures are found in both the male and female external genitalia?
a genital tubercle, urogenital fold, and labioscrotal fold/genital folding.
Androgens from the developing ___ (mostly T converted peripherally to DHT) stimulate differentiation of male external genitalia. What happens in females?
testes
The absence helps females develop their external genitalia
What do the following develop into in the male and female?
genital tubercle
urogenital fold
labioscrotal folds
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
T/F. The brain is also sexually differentiated due to the effects of T aromatized to E2 in the developing male.
True
___ ___ ___ is due to an adrenal enzyme deficiency that results in excess production of adrenal androgens.
Congenital adrenal hyperplasia
For example, what happens if the enzyme 21α hydroxylase is mutated?
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.
If a female fetus (XX) has been exposed to T, what will happen to her phenotype?
phenotype is virilized or more male than female depending on severity
If a female fetus (XX) has been exposed to T, what will happen to her gonads and internal genitalia?
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.
What is another name for 5α-reductase deficiency?
guevodoces
The development of what structures is dependent on DHT?
penis
scrotum
prostate gland
What happens with 5α-reductase deficiency? What is the genotype for individuals with this deficiency?
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
What is the phenotype of 5α-reductase deficiency?
female at birth until early puberty
What is the effects on the gonads and internal genitalia?
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.
What causes Testicular feminization or androgen insensitivity?
lack of lack functional androgen receptor (used by both T and DHT)
T/F. There is no differentiation of genitalia in Testicular feminization or androgen insensitivity because there is no functional receptor.
True.
If the genotype in Testicular feminization or androgen insensitivity is XY, why is the phenotype female?
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
What are the effects of the gonads and internal genitalia in Testicular feminization or androgen insensitivity individuals?
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.
There is a dramatic increase in circulating concentrations of steroid hormones during pregnancy due to ___ production.
placental
If the corpus luteum regresses after ~3 months, what supports luteal steroidogenesis?
hCG
Placental ___ stimulates growth of myometrium and placental ___ reduces uterine contractility and stimulates vasodilation.
E2; P
What considerations should be taken for a pregnant dental patient?
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
