General Overview of Reproductive Axis I & II Flashcards
Characteristics of reproductive axis
- Age-related component (pre-oubertal vs post etc)
- Boys and girls are different
- 2 pituitary hormones(FSH & LH)
- 3 gonadal hormones that feedback
- Gonads are not the only source in the body for the 3 hormones
Structure of FSH, LH, TSH, bHcG
Same alpha unit, different Beta subunit
There are three major categories of sex steroids:
progestins, androgens, and estrogens
The major classes of steroid hormones are
glucocortocoids, mineralocorticoids, and sex steroids
Principle sources of sex steroids include:
the gonads, the adrenal cortex, and the placenta.
what Peripheral tissues play key roles in the conversion and metabolism of sex steroids?
the skin, liver and adipose tissues
Number of carbons in steroid hormones:
- glucocortocoids such as cortisol (C-21),
- mineralocorticoids such as aldosterone (C-21),
- sex steroids which include
- progestins (C-21),
- androgens (C-19), and
- estrogens (C-18).
of carbons in cholesterol?
27, progressively reduced to form steroid hormones
Summarize conversion of cholesterol to steroid hormone
By a process which includes a reduction in the size of the hydrocarbon side-chain and hydroxylation of the 4-ring steroid nucleus, resulting in a structurethat is a 21-carbon compound known as pregnenolone. Pregnenolone is then converted into all other sex steroids
-Rate limiting step is catalyzed by side chain cleaving enzyme, 20, 22 desmolase, in mitochondrial membrane.
Progestins
- 21 carbons
- Include: pregnenolone, 17-alpha-hydroxy-pregnenolone, progesterone, and 17-alpha- hydroxy-progesterone (17-OH-P)
- precursors for the production of aldosterone and cortisol by the adrenal gland
Key functions of progesterone
growth and development of the tissues and organs related to ovulation, menses, pregnancy, and lactation
Androgens
-19 carbonsvia pregnenolone
-Include e testosterone, dehydroepiandrosterone (DHEA), dehydroepiandrosterone-sulfate (DHEA-S), dihydrotestosterone (DHT), and androstenedione.
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Major source of testosterone
95% gonads, rest is adrenal
5-alpha-reductase
the enzyme which converts testosterone to dihydrotestosterone (DHT) in target cells such as those located in the prostate and skin (30-50 times more active that testosterone)
Effect of testosterone
- androgenic: growth and development of the internal and external genitalia, the development and maintenance of secondary sex characteristics, spermatogenesis, and sexual fantasies and libido. and sebum
- anabolic: growth-promoting effects on somatic tissues such as bone and muscle
Feedback regulation of hypothalamic – pituitary – testicular axis,
testosterone acts as a key feedback inhibitor at the levels of hypothalamus and pituitary
Estrogens
- 18-carbon sex steroids
- Androgens are converted into the estrogens
- The estrogens synthesized in the human body include estrone (E1), estradiol (E2) and estriol (E3) (hydroxyl groups.
- estradiol is the most potent and estriol (from placenta only) is the least.
- Estrogens affect uterus, the ovaries, and the breasts.
Aromatase
Aromatase is present in the gonads and in various peripheral tissues including adipose tissue, liver, ands the CNS. Converts androgens to estrogens.
-Key functions of estradiol include
the growth and development of the tissues and organs related to ovulation, menses, pregnancy, and lactation.
Feedback regulation of the hypothalamic – pituitary – ovarian axis
, estradiol acts as a key feedback inhibitor at the levels of hypothalamus and pituitary.
Plasma proteins that bind sex hormones
albumin, sex hormone binding globulin (SHBG), and corticosteroid binding globulin (CBG).
2 key concepts of hypo-pit-gonad axis
- Feedback regulation
- 2 cell synthesis in gonads
Reason for GnRH secretion pulsatility is
key to the physiologic stimulation of the anterior pituitary as constant administration of GnRH actually suppresses the pituitary response
primary hormone regulators of gonadal function in both sexes.
FSH and LH from ant pit
LH and FSH stimulate the production of
sex steroids and inhibin
The sex steroids exert negative feedback control on the reproductive axis at both the
hypothalamic and pituitary levels.
Inhibin exerts negative feedback control on the reproductive axis exclusively at the level of
the pituitary.
When is +ve feedback exerted?
ovarian estradiol At midcycle in ovulatory women,
, leading to a surge in FSH and LH.
gonadal sex steroid production and gametogenesis in testes
Leydig and Sertoli cells.
gonadal sex steroid production and gametogenesis in ovaries
theca and the granulosa cells
male Leydig and female theca cells common features. These include the
-Interstitial cells
presence of LH receptors,
-ability to make androgens,
-inability to make estrogens due to the absence of aromatase.
male Sertoli and female granulosa cells common features
immediately adjacent to the developing gametes and
- presence of FSH receptors,
- ability to make inhibin,
- ability to convert androgens into estrogens due to the presence of aromatase.
The Leydig cells
- occupy the interstitial layer surrounding the seminiferous tubules. ,
- Leydig cells produce ~95% of the testosterone (from cholesterol) in males In response to LH.
- resulting testosterone acts on the Sertoli cells to support spermatogenesis.
LH stimulates the rate-limiting conversion of cholesterol into pregnenolone in two ways:
by increasing the amount of desmolase and by enhancing the affinity of desmolase for cholesterol.
The Sertoli cells
- support or nurse cells of the developing spermatozoa.
- organized into a tubular epithelium known as the seminiferous tubule (tight gap junctions between adjacent Sertoli cells).
- Maturing spermatogonia are located between adjacent Sertoli Cells.
- primary source of inhibin in males
FSH binding to Sertoli cells effects
increased production of androgen binding protein, enhanced conversion of testosterone from the Leydig cells into estradiol, and the production of inhibin.
theca cells
- are located in the ovarian stroma surrounding the follicles
- theca cells produce progesterone and androgens.
- lack aromatase and therefore the capacity to produce estrogens.
- Androstenedione from the theca cells must therefore diffuse into nearby granulosa cells for estrogen to be produced.
The ovarian granulosa cells
- are in direct contact with the oogonia
- Granulosa cells lack the enzyme which converts progesterone into androgens.
- Progesterone from the granulosa cells must therefore diffuse to the theca cells where it is converted into androstenedione.
