Intro to Repro system Flashcards
3 major categories of sex steroids
- Progestins
- Androgens
- Estrogens
Extra-gonadal tissues that secrete various sex steroids
- Placenta
- Dermis
- Adrenal glands
- Adipose tissue
Which is a glucocorticoid and which is mineralocorticoid?
Cortisol
Aldosterone
Cortisol: Glucocorticoid
Aldosterone: mineralocorticoid
How many carbons in:
Cholesterol
Cholesterol: 27 C
Gonadal cells (Ie: Leydig cells) cans synthesize cholesterol via which 2 ways?
- De novo from co-enzyme A
2. Derive cholesterol form LDL in circulation
RLS in steroid synthesis involves which enzyme?
20, 22 desmolase (SCC Enzyme) in mitochondria
- this is the first step of converting Cholesterol (27C) to Pregnenolone (21C) in the mitochondria
*pregnenolone is then converted into all other sex steroids
Cholesterol is converted to ______ in the first step of steroid synthesis. ______ is then converted into all other sex steroids.
Pregnenolone (21C)
Pregnenolone (21C)
Progestins
- how many carbons?
- Which hormones?
- Can be precursor for production of what?
(yellow box)
4 progestins - all 21 Cs
(1) Pregnenolone →
(2) 17a-Hydroxypregnenolone OR!!
(3) Progesterone → which can get converted to
(4) 17a-Hydroxyprogesterone
Can be precursor for aldosterone and cortisol by adrenal glands
How many carbons are in aldosterone and cortisol?
21Cs
What are the major circulating progestins in males and females?
Females: progesterone
Males:
17a-Hydroxyprogesterone
Good marker for late-onset congenital adrenal hyperplasia
17-hydroxy progesterone
discussed in other lecture
Progestins affect almost all tissues in the body, most notably which ones?
- the exact same 3 as Estrogens:
- uterus
- ovaries
- breasts
- growth and development of the tissues and organs related to ovulation, menses, pregnancy, and lactation.
How many carbons are in androgens? Where does it come from?
What are the major androgens that are synthesized in the human body?
19C
Derived from cholesterol via pregnenolone
(same as estrogen)
- testosterone
- dehydroepiandrosterone (DHEA)
- DHEA-S
- DHT
- Androstenedione
*note that estrogen is 18C
Where is the majority of testosterone produced in males?
Males:
- 95%: Leydig cells in testes
- 5%: adrenal cortex
Where is the majority of DHEA and DHEA-S produced?
Adrenal cortex
- excellent marker of adrenal androgen activity
What is the precursor for ovarian estradiol production by the GRANULOSA CELLS?
Androstenedione from the theca cells in the ovaries
Enzyme that converts Testosterone to DHT
5 a-Reductase
(mainly in testosterone target cells)
*DHT is 30-50x more active and cannot be converted to estrogens
Do androgens have significant effects on the growth of the reproductive system? What about testosterone?
Androgens No
Testosterone yes
- affects almost all tissues in the body
Difference between androgenic and anabolic effects of testosterone
- Androgenic:
impacts growth and dev of internal and ext genitalia
- dev of 2ndary sex char, spermatogenesis, sexual fantasy and libido
- stuff you know - Anabolic:
Growth promoting effects on somatic tissues (BONE AND MUSCLE)
What are the key feedback inhibitors for:
- Hypothalamic-Pituitary-ovarian axis
- Hypothalamic-Pituitary-testicular axis
- Progesterone and estradiol
2. Testosterone
How many carbons are in Estrogen? What is it derived from?
18C
Cholesterol via pregnenolone
same as androgens
- 2 ex of estrogens: estrone, estradiol
How are estrogens produced from pregnenolone? What enzyme is involved in that final conversion?
Cholesterol → Pregnenolone → Progestins → Androgens → Estrogens (via aromatase)
Estrogens:
E1
E2
E3
Names and which one is most potent
E1: estrone
E2: estradiol
E3: estriol
*one, two, three OH groups
E2 is most potent, E3 is least
Where is estradiol produced in males and females
Males:
Seroli cells of testes
Females:
Granulosa cells of ovary
Where is estrone (E1) and Estriol (E3) produced?
E1: adipose tissue
E3: important placental product
Why is pulsatile secretion of GnRH the key to physiologic stimulation of the anterior pituitary?
Constant administration of GnRH actually suppresses the pituitary response
When do FSH and LH reach their peaks?
Shortly before ovulation
LH and FSH stimulate the production of which hormones?
Where do they work?
Sex steroids
- negative feedback control on hypothalamus and pituitary
Inhibit
- neg feedback control on pituitary
*at midcycle, estradiol also exerts pos feedback mech on pit gland → FSH + LH surge
Two imp cells in testis + ovary
Testis:
- Leydig
- Sertoli
Ovary:
- Theca
- Granulosa
- Male Leydig and female Theca are interstitial cells and are similar
- Sertoli + granulosa cells are similar
Things that Male Leydig and female Theca are interstitial cells and share
- Able to make androgens + progesterone in presence of LH secretion/rcptrs
- Unable to make estrogens due to absence/lack of aromatase
(fxn of sertoli and granulosa cells)
Things that Male Sertoli and female Granulosa cells have in common
Able to make inhibin in presence of FSH receptors
Able to convert androgens into estrogens due to presence of aromatase
How does LH stimulate the rate limiting conversion of cholesterol into pregnenolone?
- Increasing the amt of desmolase
2. Enhancing the affinity of desmolase for cholesterol
Spermatogenesis requires which hormones
LH FSH Leydig cells Sertoli cells Testosterone
Sertoli cells are organized into tubular epithelium known as ________. It is supported by the presence of _____ between sertoli cells.
Seminiferous tubules
Tight gap jxns
*seminiferous tubules are responsible for maturation of gametes
Effects of FSH binding to Sertoli cells
- Increased production of androgen binding protein
- Enhanced conversion of testosterone (from Leydig cells) into estradiol
- Production of Inhibin
*sertoli cells are the primary source of inhibin in males
The gametes and their surrounding granulosa cells are called ________. The _______ follicle matures each month.
Primordial follicles
Dominant follicle
Oogenesis and ovulation require which hormones and cells?
- LH
- FSH
- Testosterone
- Estradiol
- Granulosa cells
- Theca cells
Granulosa cells lack the enzyme which converts progesterone into androgens, well then how the hell do androgens get produced in females?
Progesterone from the granulosa cells diffused to the theca cells →
converted to androstenedione
→
theca cells lack aromatase →
androstenedione diffuses back to granulosa cells →
conversion to estradiol
LH binds to which cells and FSH binds to which cells?
LH binds to Leydig Cells
- L → L
FSH binds to Sertoli cells
- S → S
The biological activity of LH and ____ are very similar. So much so, that it is often substituted for LH because it is much more readily available.
hCG
*hCG can be used therapeutically to initiate spermatogenesis in azoospermic or oligospermic men
FSH leads to the synthesis of _______, which is secreted into the luminal space of the seminiferous tubule, near the developing sperm cells. ________ Helps to keep local testosterone levels high.
Androgen Binding protein (ABP)
Androgen Binding protein (ABP)
How is FSH involved in converting Testosterone into estradiol in men?
It causes the synthesis of Aromatase.
Testosterone diffuses from Leydig cells → Sertoli cells
- In Sertoli cells, aromatase converts T into Estradiol
4 things that FSH stimulates Sertoli cells to synthesize
- Androgen binding proteins (ABP)
- Aromatase
- Growth factors
- Inhibins
*FSH may also increase the fertility potential of sperm!
Which one inhibits LH, which one inhibits FSH:
Testosterone vs Inhibin
Testosterone inhibits pulsatile release of LH
- by inhibiting pulsatile release of GnRH
Inhibin inhibits FSH secretion
(FSH stimulates Sertoli cells to make inhibin, and inhibin “inhibits” FSH secretion)
Two immediate precursors for Testosterone and two hormones that can come from Testosterone
Androstenedione or
Androstenediol
→
Testosterone
Testosterone →
Estradiol or DHT
All of the DHEA in male plasma originates from where?
Adrenal glands
- Can test adrenal fxn using DHEA
