Biochemistry of the Main Gonadal Hormones

Question 1

why are the gonads described as bifunctional organs?

Answer 1

• produce germ cells
• produce sex hormones
  *

Question 2

What are the main gonadal hormones in males and females?

Answer 2

Female= oestrogens and progestogens

Males= androgens (testosterone and DHT)

Question 3

Ovaries produce… ?

Answer 3

Ova

Question 4

How many germ cells are present at birth in the female?

Answer 4

All of them -

there are 1-2 million germ cells present at birth in the female and no new ones are produced , you loose a lot of the immature germ cells over time - then 1 is ovulated every month for the entire fertile life cycle

Question 5

Do men fluctuate in hormones - like a cycle?

Answer 5

no - they are rather constant in hormone levels

Question 6

testes produce…?

Answer 6

spermatazoa

Question 7

what are the 5 major classes of steroid hormones?

Answer 7

they are derived from cholesterol and pregnenolone

• progestagens
• glucocorticoids
• mineralocorticoids
• androgens
• estrogens

Question 8

what structure releases gonadotropin releasing hormone in a pulsatile secretion?

Answer 8

Hypothalamus

Question 9

what hormone is responsible for the development of the graafian follicle?

Answer 9

FSH

Question 10

What hormone is responsible for the rupture of the follicle and the release of the egg?

Answer 10

the LH

Question 11

what importance does the corpus luteum ( remnant of the follicle) have in the ovarian cycle?

Answer 11

it can produce estrogen and progesterone - maintains a pregnancy

Question 12

what is the rational for using estrogens and progesterones as birth control?

Answer 12

they have a negative feedback release which block the effects of the gonadotropin releasing hormone

Question 13

when does the menstrual cycle start?

Answer 13

Day 1 of menses - shedding endometrium

Question 14

What is the ‘follicular phase’ ?

Answer 14

phase in which the graafian follicle matures - and proliferation of the endometrium (FSH leads to development of the follicle and the follicle itself releases estrogen)

gradual increase in estrogen leads to the proliferation of the endometrium

Question 15

What occurs on day 14 of the mestrual cycle?

Answer 15

Ovulation - surge in LH- ruptures the follicle and ovulation occurs as a result -

Question 16

What is the ‘luteal phase’ how long does it last?

Answer 16

it lasts from day 15- 28

if no implantation - progesteron secretion stops and induces menses eventuallly

if fertilization- implantation- corpus luteum continues to secrete progesterone until the placenta is formed and functional and able to take over production of progesterone

Question 17

the pulses of GnRH control what?

Answer 17

they control the peak of LH and FSH levels

Question 18

what is the ‘secretory’ phase of the endothelium?

Answer 18

after the proliferative phase, the endometrium begins to prepare itself for implantation -

there is a slight increase in the body temperature during ovulation

Question 19

estrogens are produced where?

Answer 19

ovaries/placenta in women

testis in men

adrenal cortex in both sexes

Question 20

what are the primary roles of estrogens in the body?

Answer 20

Development and maintenance of secondary sex characteristics

–Enlargement of breasts

–Growth of body hair

–Greater development of thigh muscles behind the femur, rather than in front of it

–Widening of hips; lower waist to hip ratio than adult males, on average

–Increased secretions of oil and sweat glands

–Changed distribution in weight and fat; more subcutaneous fat and fat deposits mainly around the buttocks, thighs and hips

•Control the reproductive cycle

–Coordinate the ovarian and uterine cycles

•Stimulate linear bone growth – puberty

Question 21

what are the 3 main endogenous estrogens?

Answer 21

E1 = estrone = 10% - dominant estrogen in menopause

E2 = estradiol= 17beta estradiol = 80% - primary estrogen and the most potent one

E3= estriol = 10% produced by the placenta during pregnancy

* when we refer to estrogen in the medical context most of the time we’re referring to estradiol b/c it’s most potent and highest concentration

Question 22

what regulates the synthesis of estradiol?

Answer 22

regulated mainly by FSH

Question 23

estrogens produced peripherally are controlled by what process?

Answer 23

aromatisation

Question 24

What is Aromatase?

Answer 24

it is the enzyme responsible for the key steps in the biosynthesis of peripheral estrogens (primary source of estrogen in post-menopausal women)

• this is why aromatase inhibitors are very effective in women post-menopause with estrogen receptor positive breast cancer

Question 25

aromatase converts what?

Answer 25

1. converts testosterone to estradiol in the ovary = predominant source of estrogen in premenopausal women 2. conversion of androstenedione to estrone in peripheral adipose tissue - predominant source of estrogen synthesis in postmenopausal women

Question 26

what does estrogen do?

Answer 26

_•Fertility control -_ ovum maturation/ development of the ovum/follicular unit. Timing of follicular phase is controlled by Estradiol _•Preparation of uterus for implantation_ –proliferation/vascularisation of endometrial cells –induction of progesterone receptors to allow progesterone response during luteal phase _•Inhibit FSH release,_ negative feedback on AP - basic rational for using estrogen containing contraceptive _•Metabolic action_ –Mineralocorticoid-like - retention of Na+ and water _•Lipids_ –Increase [HDL] in plasma –Decrease [LDL], [cholesterol] _•Increase coagulability of blood_ –Increases production of a number of clotting factors (2,5,7 and 9)- this can lead to DVTs and PEs _•Maintains bone density and elasticity of skin & blood vessels_

Question 27

what is the primary progesteren we see in females?

Answer 27

progesterone

Question 28

what produces progesterone in women ?

Answer 28

secreted by corpus luteum -and placenta during pregnancy - small amounts made by testes and adrenal cortex in both sexes

Question 29

what are the hormonal effects - of progesterone?

Answer 29

* Hormonal effects: * maturation of the endometrium * supports gestation and embryogenesis

Question 30

Why do we give a combined estrogen/progesterone contraceptive?

Answer 30

b/c estrogen has profound endometrium proliferative effects, and progesterone counteracts this by inducing maturation of the endometrium

Question 31

where are gonadotropins produced/secreted?

Answer 31

Produced & secreted by anterior pituitary or chorion & placenta –Follicle stimulating hormone (FSH) –Luteinising hormone (LH) –Human chorionic gonadotropin (HCG)

Question 32

what are the three gonadotrophic hormones? How do they differ?

Answer 32

All 3 hormones are dimeric► a & b subunits * a subunit is common * b subunit differs - biological activity resides * b subunit in HCG and LH very similar [90% homology] * same target tissue (corpus luteum) and cellular response (↑ progesterone)

Question 33

what is GnRH?

Answer 33

GnRH - gonadotrophic releasing hormone = peptide hormone, synthesized and released from neurons within the hypothalamus GnRH secreted in a pulsatile manner from hypothalamus controls secretion of FSH and LH by AP in females

Question 34

What controls FSH and LH synthesis and secretion?

Answer 34

FSH & LH synthesis and secretion are controlled by the size and frequency of GnRH pulses, as well as by feedback from androgens and oestrogens: –low-frequency GnRH pulses lead to FSH release –high-frequency GnRH pulses stimulate LH release

Question 35

how does GnRH pulses change in the female cycle? men? during childhood?

Answer 35

In females, GnRH pulses frequency varies during the menstrual cycle, with large surge just before ovulation * In males, GnRH is secreted in pulses at a constant frequency * During childhood, GnRH activity very low, activated at puberty

Question 36

in men, what two hormones are controlled by GnRH?

Answer 36

GnRH increases production of FSH and interstitial cell stimulating hormone (AKA ICSH or sometines refered to as LH)

Question 37

what is the more potent metabolite of testosterone? what enzyme converts testosterone to this metabolite?

Answer 37

Dihydrotestosterone - testosterone is converted to this by 5 alpha reductase

Question 38

what is the main androgen produced- where is it produced?

Answer 38

testosterone = major testicular androgen produced by interstitial cells of leydig in testis

Question 39

how much Dihydrotestosterone is produced compared to testosterone concentration in men?

Answer 39

DHT is present at 1/10th concentration of testosterone in blood

Question 40

What is the major source of androgeneic activity in females?

Answer 40

androstenedione - produced by adrenal cortex - far less potent than testosterone but major source of androgenic activity in females

Question 41

what are the secondary sex characteristics of men?

Answer 41

* Growth of facial & body hair * Greater mass of thigh muscles in front of the femur, rather than behind it * Enlargement of larynx and deepening of voice * Increased stature; adult males are taller than adult females, on average * Heavier skull and bone structure * Increased muscle mass and strength * Broadening of shoulders and chest; shoulders wider than hips * Increased secretions of oil and sweat glands * Higher waist to hip ratio than females or prepubescent males, on average

Question 42

What occurs in inherited deficiency of 5 alpha reductase?

Answer 42

prevents synthesis of DHT from testosterone - (very rare condition) - during embryogenesis DHT essential role in formation of male external genitalia - affected boys born with ambiguous external genitalia - although testes and internal wolffian ducts are present - full virilizaiton takes place at puberty (aka penis at twelve syndrome) - pretty rare condition

Question 43

what is congenital adrenal hyperplasia?

Answer 43

most common defiicency - ## Footnote Deficiency of e.g. 21-a-hydroxylase or 11b-hydroxylase –Enzymes required for synthesis of corticosteroids but not androgens –Corticosteroid synthesis blocked, **overproduced progestogens are diverted into androgen synthesis** 1. Life threatening electrolyte imbalance 2. Ambiguous external genitalia in girls, precocious puberty in boys (early puberty as early as 9 yr. old)