Reproductive Physiology Flashcards
MIH ( AMH)
Mullerian-inhibniting hormone (MIH)
also called
anti-Mullerian hormone (AMH)
X → DHT
a rxn catalyzed by 5a-reductase
X is T (testosterone)
DHEA
(de. hydro.epi.andro.sterone)
de. hydro.epi.andro.sterone
- Formed as a product of the 2nd rxn of sex steroid synthesis.
Note: It functions as a metabolic intermediate in the biosynthesis of the androgen and estrogen sex steroids both in the gonads and in various other tissues.
SRY
Sex-determining Region of Y chromosome
List male androgens:
Testosterone (T)
- androstenedione (precursor of extraglandular estrogen in men)
- DHEA
- DHT
genital swelling (- )DHT/f
labia majora
which one of the following can not be detected during 6-7 wks gestation period:
A- germ cells
B- seminiferous tubules
C- leydig cells
D- sertoli cells
C- leydig cells appear later- 8-9 weeks
Choice A might have been difficult to eliminate. Indirectly, it’s been given that during 6-7 weeks sertoli cells enclose germ cells.
Normal levels of testosterone (T), Estrogen (E) and estradiol 17B depends on:
age
gender
health status
time of the day
women: phase of menstrual cycle
Other hormones in the same family as LH/FSH
TSH and hCG
•FSH, LH, TSH, hCG are all are glycoproteins with à and ß subunits
- à chains of TSH, hCG. LH and FSH are the same
- ß chain confers specificity
external genitalia-f
clitoris
labia mjora
labia minora
lower vagina
Morris Syndrome
Androgen insensitivity syndrome
Female differentiation at 9 weeks:
Enumerate the events
- Activation: XX activation (both)
- Mitosis: Germ cells → oogonia
- Meiosis: oogonia
- Support: cells surrounded by granulosa cells and stroma
- Theca cell development from stroma
- Meiosis arrest in late prophase
Androgen insensitivity syndrome
Mode of inheretance
Genotype and phenotype
X-Linked recessive due to the absence of androgen receptors on target tissue.male genotype but appears as female phenotype
Genotype: XY
What happens to Wolffian ducts in the absence of Testosterone?
- Wolffian duct regression
- Mullerian duct development ( into fallopian tubes, uterus cervix and upper 1/3 of vagina).
92AA long GnRH
preprohormone
preprohormone → prohormone → decapeptide-GnRH + GAP
precursors of theca and leydig cells
mesenchymal stromal cells
One of 2 cell types that is indifferent in both m and f; and is present in the 1st 5 week in-utero gonals.
Identify compounds A and B (sex steroid synthesis)
A → 17à-hydroxypregnenolone → B
A- pregnenolone
B- DHEA
♦ 2nd and 3rd reactions of the synthesis of sex steroids, which takes place in SER. They are also common for both m and f.
testes develop from —— via action of SRY region of Y chromosome.
primitive gonads
time period at which the external genitalia of both genders begin to differentiate
~9-10 wks
sex steroid metabolism is similar to ……….
similar to corticosteroids and mineral corticoids metabolism
- metabolized mainly in liver
- excreted in urine
- with halg life of ~30-60 min
Sex Steroid circulation (sex steroids and progestrone)
Sex steroids are bound to SSBG or albumin.
Sex steroids: testostrone and estrogen
Progestrone circulate bound to corticosteroid binding globulin (CBG).
MIH (AMH) is produced by
sertoli cells
genital tubercle (-) DHT/f
clitoris
the common tissue of labia majora and scrotum
genital swelling
Total # of Cs for male sex steroids:
19
Specific events of male gonadal differentiation:
- 6-7 weeks
- 8-9 weeks
In males at 6-7 wks
- Semineferous tubules form
- sertoli cells enclose germ cells
8-9 wks
- Leydig cells appear
The time periods at which testes are distinguishable and functional
- Distinguishable in 7 weeks
- Fully functional in 14-15 wks( additional 7-9 weeks).
Testosterone paracrine action on Wolffian ducts
Development of:epididymis, vas deferens, seminal vesicles and ejaculatory ducts.
During female gonadal differentiation (~9wks) some of these cells undergo meiosis:
oogonia
The source function of testostrone during development of male internal genitalia
Testosterone (produced by leydig cells) act in paracrine manner to stimulate development of wolffian ducts into epididymis, vas deferens, seminal vesicles and ejaculatory duct.
The common tissue of clitoris and glans penis:
genital tubercle
Regardless of the genetic make up, prior to 6 weeks gestation, the fetus has indifferent gonads that have formed from —–
the genital ridges
Note: at 6 wks gestation, migratory germ cells invade the genital ridges.
From —- cell, theca cells develop.
Hint- 9wks, female gonadal differentiation
stroma
GnRH binds the plasma membrane of ——- in pituitary and stimulates the release of both FSH and LH.
gonadotroph
5-alpha-reductase converts testosterone to this compound
DHT
The common target tissues of DHT in both m/f:
Genital tubercle
Genital swelling
Urethral fold
Urogenital sinus
Precursor of extraglandular estrogens in men
Andro.sten.edione (made from DHEA)
Note 1 : both ovaries and testies produce estrogen and androgen. Androgens produced from adrenal cortex in both sexes gets convrted to estrogen in adipose and other extragonadal external adrenal tissues.
Note 2: Androstenediol, or 5-androstenediol (abbreviated as A5 or Δ5-diol), also known as androst-5-ene-3β,17β-diol
The time frame whithin which the androgenic hormones take effect in women
After menopause androgenic hormones are produced by adrenals
The period by which the leydig cells appear during m. gonadal differentiation
By 8-9 week
A period of gonadal differentiation, in which (both m/f) in-utero gonals are indifferentiated
1st 5 week- indifferent gonals
genital tubercle (+) DHT (m)
glans penis
T is produced by
leydig cells of testes
precursor of sertoli cells (cell type found in the first 5 week)
coelomic epithelial
True hermaphrodites
true hermaphrodites are individual with both male and female gonads.
urogenital sinus + DHT (m)
prostate gland
69AA GnRH
prohormone
preprohormone (92aa) → prohormone (69aa) →
decapeptide-GnRH (10aa) + GAP (GnRH associated peptide)
genetic state: XY, normal
- Gonads
- Mullerian ducts
- Wolffian ducts
- Ext. Genitalia
- testes
- regressed MD
- developed WD
- Male
Meta female
Dysgenic ovary
MD-developed
WD- regressed
external genitalia: female
The common linage for the genitalia differentiation is based on the presence of ——— .
dihydrotestosterone DHT
The common tissue of lower vagina and prostate gland
urogenital sinus
DHT
dihydrotestosterone
The common linage for the genetical differentiation is based on the absence of DHT.
T → DHT (enzyme: 5a reductase)
male determinant chromosome
Y
estrogens are produced in
ovaries and testes
ovaries: large amt (small amt of T)
Testies: Small amt ( L. amt T)
Hormones required for libido in women
androgens
CBG
corticosteroid binding globulin
The two internal ducts ithat are present in an early embryo, (regardless of the sex) are:
Wolffian duct
Mullerian duct
mullerian duct future
female internal re[productive tract
Locations/sub-location of GnRH production
arcuate nucleusandpreoptic are of hypothalamus
Location of sex steroid production
Testes and ovaries (functioning as endocrine glands , in addition to gamete production)
precursor of extraglandular estrogens in men
androstenedione
GnRH (decapeptide) & GAP
- Synthesis
- Processing
1- synthesis: as preprohormone (92 AA) in arcuate nucleus and preoptic area of hypothalamus.
2- Processing: 2 cleavages
- 1st cleavage: pro-hormone (69 AA)
- 2nd cleavage: a 56 AA, GAP- GnRH Associated Protein.
3- GnRH as a decapeptide with 10 AA.
Note: both GAP and GnRH are secreted into portal circulation.
At 6 week gestation the genital ridges are invaded by
migratory germ cells
- Prior to 6 wks, the fetus has indifferent gonads with genital ridges.
location for the following conversions:
Androstenediol to andsosterone
T to DHT
SER
genetic state: XO, Turners
- Gonads
- Mullerian ducts
- Wolffian ducts
- Ext. Genitalia
- Streak
- MD- developed
- WD- regressed
- Female
The structures that are formed from mullerian duct in the absence of testosterone:
fallopian tubes
uterus
cervix
upper 1/3 of vagina
(in the absence of T, female is the “default” pattern)
Two distinct roles of reproductive system
1- endocrine ( reg’ by HPG axis) and 2- reproductive
SSBG
steroid binding globulin (circulate sex steroids)
Reactions catalyzed by 17β-hydroxysteroid dehydrogenases
Androstenedione is converted to testosterone, DHEA is converted to androstenediol, and estrone is converted to estradiol by the 17β-hydroxysteroid dehydrogenases
DHT
Dihydrotestosterone
coelomic epithelial
during the first 5 week- precursors of granulosa and sertoli cells
genetic state: XY, No Androgen receptor
- Gonads
- Mullerian ducts
- Wolffian ducts
- Ext. Genitalia
- Testes
- MD- regressed
- WD- regressed
- Female
development of male internal genitalia depends on these two hormones produced by fetal testes:
- testosterone
- MIH- Mullerian- inhibiting hormone
genetic state: XY, Reduced Testosterone
- Gonads
- Mullerian ducts
- Wolffian ducts
- Ext. Genitalia
- Testes
- MD- regressed
- WD- Regressed/Variable
- M/F
urethral folds ( - )DHT (f)
labia minora
FSH/LH structure
•FSH, LH, TSH, hCG are all are glycoproteins with à and ß subunits
à chains of TSH, hCG. LH and FSH are the same
ß chain confers specificity
Reproductive (exocrine) function of reproductive system
- Gametogenesis
- male: continuous
- female: cyclical
- Maintnance of:
- reproductive tract
- secondary sex characteristic
GAP
GnRH associated peptide (hormone).
Estrogens (3 different types):
Estradiol 17B, estrone, estriol.
Regulation of endocrine function of reproductive system
Hypothalamic pituitary- gonadal axis (HPG axis) In males: HPT (testicular ) axis
After X chromose activation, germ cells undergo mitosis and form
oogonia
cell(s) responsible for estrogen production (f):
granulosa and thecal
When does f. gonadal differentiation begin?
~ 9 weeks
Source of androgenic hormones in women
Adrenal Cortex
locations of progesterone production
Initially: corpus luteum
later: placenta
location and function of SRY gene
located on the short arm of Y chromosome
•Testes develop from primitive gonads via action of SRY region of Y chromosome
Klinefelters
XXY with dysgenic testes
MD regressed
WD developed
external genialia: male
Total # of carbon of estrogens
18
cell types of indifferent m/f gonads during the first 5-week of pregnancy
- coelomic epithelial
- mesenchymal stromal cells
The genes that encode androgen receptors are located on this chromosome
X
The common tissue of labia minora and penile shaft:
urethral folds
External genitalia - m
glans penis
scrotum
penile shaft
prostate gland
During development of male internal genitalia ,testostrone is produced by
Leydig cells
major organ for sex steroid metabolism
mainly liver
Hormones that affect the differential secretion of LH and FSH (in addition to GnRH)
- testosterone
- estrogen
- activin
- ihibin
manifestation of Morris syndrome(46XY)
genetic male- phenotype female (ext. genitalia)no internal tract
blind-ending vagina
greater than average height
infertile
absent or very slight pubic/axial hair.
hCG
Human chorionic gonadotropin
wolffian ducts future
male internal reproductive tract
An X-linked recessive defect that leads to the absence of androgen receptors on target tissues.
Androgen insensitivity syndrome.
male genotype- female phenotype
Reactions catalyzed by 5a-reductase (male specific pathways)
Location
Reactions:
androstenediol —> androsterone (C19)
Testosterone —> DHT
5a-reductase mainly in testostrone target cells
Dihydrotestosterone, or 5α-dihydrotestosterone, also known as androstanolone or stanolone, is an endogenous androgen sex steroid and hormone.
Androsterone, or 5α-androstan-3α-ol-17-one, is an endogenous steroid hormone, neurosteroid, and putative pheromone. It is a weak androgen with a potency that is approximately 1/7 that of testosterone. Androsterone is a metabolite of testosterone and dihydrotestosterone.
urogenital sinus (-) DHT/f
lower vagina
individuals with the gonads of one sex but the external genitalia of the opposite sex or both sexes
Pseudohermaphrodites
Estrone (E1) and Estradiol (E2) are converted to —— in the liver.
estriol (E3)
Note: estradiol 17B, Estrone and Estriol are produced by granulosa and thecal cells of ovary.
Rhythmic secretion of this hormone influences rate of expression for genes encoding the à, ßLH and ßFSH subunits.
Rhythm of GnRH secretion influences rate of expression for genes encoding the à, ßLH and ßFSH subunits.
genetic state: XY, Red. 5-a-reductase
- Gonad
- Mullerian ducts
- Wolffian ducts
- Ext. Genitalia
- Testes
- MD- regressed
- WD- developed
- M/F
GAP secretion and function
secreted simultaneously from hypothalmic neurons with GnRH into portal circulation.
Possible Role: inhibition of prolactin secretion
Progesterone circulation
Bound to CBG
unlike estrogen and testostrone that circulate bound to SSBG or albumin.
active stimulation and transformation of wolffian duct into male reproductive tract is required for:
development of testes
genetic state: XX, normal
- Gonads
- Mullerian ducts,
- Wolffian ducts
- Ext. Genitalia
- ovary
- MD- developed
- WD- regressed
- Female
The stage (meiosis) at which female cells are arrested at:
late prophase
Primary oocytes arrested in prophase I before birth.