REB 14. Biochemistry of the Main Gonadal Hormones

Question 1

What are the gonads?

Answer 1

Gonads: bifunctional organs that produce germ cells and the sex hormones
e.g. ovaries and testes

Question 2

What are the 2 types of gonadal hormones that are present in females?

Answer 2

[1] Oestrogens
[2] Progestogens
- progesterone is the most common progestogen

Question 3

How are the female gonadal hormones released?

Answer 3

• monthly cycle of hormone levels
• all germ cells present at birth (around 1 to 2 mllion)
• no new ovums are produced
• around 400 ova are ovulated in the span of a woman’s life

Question 4

What are the gonadal hormones that are present in males?

Answer 4

Androgens - testosterone + DHT (dihydrotestosterone)

Question 5

What is DHT?

Answer 5

Dihydrotestosterone - a potent metabolite of testosterone

Question 6

How are the male gonadal hormones released?

Answer 6

• constant levels of hormones

- continuous production of sperm

Question 7

What produces ova?

Answer 7

Ovaries

Question 8

What produces spermatozoa?

Answer 8

Testes

Question 9

What hormone contains an aromatic ring?

Answer 9

Estrogens are the only hormones that contain an aromatic ring

Question 10

What is the name of the axis that controls the hormones that controls the female reproductive system?

Answer 10

Hypothalamic-Pituitary-Gonado Axis

Question 11

What are the 4 stages of the menstraul cycle?

Answer 11

[1] Menses (day 1 to day 5)
- shedding of endometrium

[2] Follicular Phase (day 5 to day 13)

• ovum maturation + proliferation endometrium
• estrogen levels gradually increase

[3] Ovulation (day 14)
- surge in LH

[4] Luteal Phase (day 15 to day 28)

• increase in progesterone
• decrease in LH and FSH
• if no implantation, progesterone secretion stops, inducing menses
• if fertilization (implantation), corpus luteum secretes progesterone

Question 12

What does the corpus luteum secrete?

Answer 12

progesterone

Question 13

What is Inhibin? What is its role?

Answer 13

a hormone that is secreted by the granulosa cells (in ovary)

- inhibits secretion of FSH by anterior pituitary gland

Question 14

Where is estrogen synthesized?

Answer 14

[1] ovary
[2] placenta
[3] testes (small amount)

Question 15

What is the primary roles of estrogen?

Answer 15

[1] development + maintenance of secondary sex characteristics
[2] control the reproductive cycle
[3] stimulate the linear bone growth - puberty

Question 16

What are the secondary sex characteristics that are developed and maintained in females?

Answer 16

• enlargement of breasts
• growth of body hair
• greater development of thigh muscles behind femur
• widening of hips
• secretions of oil and sweat glands
• changed distribution in weight and fat

Question 17

What are the 3 main endogenous estrogens?

Answer 17

[1] Estrone (E1)
[2] Estradiol (E2/17beta-estradiol)
[3] Estriol (E3)

Question 18

What is the most common endogenous estrogen? Where is is synthesized and what is it regulated by?

Answer 18

Estradiol (E2) - 80%

• synthesized by ovary (non-pregnant)
• regulated by FSH
• can also be made peripherally (aromatization)!

Question 19

What is aromatization?

Answer 19

It is the creation of estrogen peripherally

Question 20

What 2 processes is the aromatase enzyme responsible for (crucial part of)?

Answer 20

[1] conversion of testosterone to estradiol in the ovary in premenopausal women

[2] conversion of androstenedione to estrone on peripheral adipose tissue in postmenopausal

Question 21

Why are aromatase inhibitors used?

Answer 21

they are frequently used as estrogens may promote some cancers
- e.g. anastrozole + letrozole

Question 22

What hormone controls the timing of the follicular phase?

Answer 22

Estradiol (E2)

Question 23

What are the actions of Estrogen? (on other hormones, metabolic actions, lipids…)

Answer 23

refer to slide 14

Question 24

From what things is progesterone secreted from?

Answer 24

[1] corpus luteum
[2] placenta during pregnancy
[3] small amounts by testes and adrenal cortex (both sexs

Question 25

What are the hormonal effects that progesterone has? [2]

Answer 25

[1] maturation of the endometrium

[2] supports gestation and embryogenesis

Question 26

What are the gonadotrophins?

Answer 26

[1] FSH
[2] LH
[3] bonus: Human Chorionic Gonadotropin (HCG)

Question 27

Where are the gonadotropins produced and secreted?

Answer 27

[1] Anterior Pituitary

[2] Chorion + Placenta

Question 28

Describe the structure of the gonadotrophic hormones (the subunits).

Answer 28

All the gonadotropins have an alpha and beta subunit (they are dimeric)

• alpha subunits are all the same
• beta subunit differs between the 3 (biological activity resides here)

*side note: the HCG and LH beta subunit is very similar (same target tissue + same cellular response)

Question 29

What hormone does the hypothalamus secrete to stimulate the gonadotrophic hormones? In what type of manner?

Answer 29

hypothalamus secreted GnRH in a pulsatile manner

Question 30

What characteristics of GnRH pulses alters the FSH and LH synthesis and secretion?

Answer 30

[1] Size
[2] Frequency
of the GnRH pulses

Question 31

If there are low-frequency GnRH pulses, this leads to…

Answer 31

FSH release

Question 32

If there are high-frequency GnRH pulses, this leads to…

Answer 32

LH release

Question 33

Compare and contrast the GnRH pulse frequency in women, men and children.

Answer 33

WOMEN:

• pulse frequency varies during the menstrual cycle
• large surge before ovulation

MEN:
- GnRH is secreted in pulses at a constant frequency

CHILDREN:

• GnRH activity is very low
• activated at puberty

Question 34

What is ICSH? What is it a “replacement” hormone of?

Answer 34

ICSH = Interstitial Cell Stimulating Hormone

- older version of LH

Question 35

What is Dihydrotestosterone (DHT)?

Answer 35

Testosterone is a precursor to this - DHT

- it is a very potent androgen

Question 36

What specific/special cells produces testosterone, a major testicular androgen?

Answer 36

Interstitial Cells of Leydig

Question 37

Explain the process of how testosterone is converted to Dihydrotestosterone (DHT). (enzymes and other molecules)

Answer 37

converted by the 5alpha-reductase enzyme + in the presence of NADPH

• occurs in certain tissues (prostate gland, seminal vesicles, epididymides, skin, hair follicles, liver + brain)

Question 38

What are the 3 major things testosterone is converted to?

Answer 38

[1] 10% DHT
[2] 0.3% Estradiol (via aromatase)
[3] 90% Inactive Metabolites

Question 39

What is Androstenedione? Where is it produced?

Answer 39

• produced by Adrenal Cortex
• far less potent than testosterone
• major source of androgenic activity in females

Question 40

List the male secondary sex characteristics.

Answer 40

[1] growth of facial + body hair
[2] greater mass of thigh muscles in front of femur (in females it is behind it)
[3] enlargement of larynx (deepening of voice)
[4] increased stature
[5] heavier skull and bone structure
[6] increased muscle mass and bone structure
[7] broadening of shoulders and chest
[8] increased secretion of oils + sweat glands
[9] higher waist to hip ratio

Question 41

Explain what happens when there is an inherited deficiency of 5alpha-reductase?

Answer 41

• important enzyme converting testosterone to DHT
• during embryogenesis, DHT plays an important role in formation of male external genitalia
• the affected boys are born with ambiguous external genitalia
• BUT, testes and internal Wolffian ducts structures are present and fine
• full virilization takes place at puberty!

Question 42

What are the deficiencies that lead to Congenital Adrenal Hyperplasia (CAH)?

Answer 42

[1] 21-alpha-Hydroxylase
[2] 11beta-Hydroxylase
- corticosteroid synthesis is blocked, the progestogens are overproduced and diverted into androgen synthesis
(a) life-threatening electrolyte imbalance (sodium and water balance)
(b) ambiguous external genitalia in girls, precocious puberty in boys
— e.g. enlarged clitoris (may look like penis)