11.29.17 Androgens

Question 1

Follicle-stimulating hormones are required:

• females: stimulate growth & development of ____, promote secretion of ____ by ovaries.
• males: required for ____ production

Answer 1

Follicle-stimulating hormones are required:

• females: stimulate growth & development of ovarian follicles, promote secretion of estrogen by ovaries.
• males: required for sperm production

Question 2

Luteinizing hormones are required:

• females: responsible for ovulation, formation of ____ in the ovary, regulation of ovarian secretion of female sex hormones
• males: stimulates cells in the testes to secrete _____

Answer 2

Luteinizing hormones are required:

• females: responsible for ovulation, formation of corpus luteum in the ovary, regulation of ovarian secretion of female sex hormones
• males: stimulates cells in the testes to secrete testosterone

Question 3

Prevalent forms of androgens are (3):

Answer 3

androstenedione, testosterone, dihydoxytestosterone.

Question 4

Androstenedione is produced by (3):

Answer 4

testes, adrenal cortex, ovaries

Question 5

Testosterone is produced by (2):

Answer 5

testes and ovaries

Question 6

Small amounts of dihydroxytestosterone is produced by:

Answer 6

adrenal cortex

Question 7

Leydig cells produce:
Sertoli cells require _____ for spermatogenesis. Sertoli cells produce ____ that negatively feedback to the anterior pituitary.

Answer 7

Leydig cells produce: testosterone
Sertoli cells require testosterone for spermatogenesis. Sertoli cells produce inhibin that negatively feedback to the anterior pituitary.

Question 8

Testosterone is converted to dihydrotestosterone by the enzyme _______.

Answer 8

Testosterone is converted to dihydrotestosterone by the enzyme 5a-reductase.

Question 9

Describe a few of the physiological effects of androgens (7):

Answer 9

-stimulates development of secondary sex characteristics
-stimulates skeletal growth and epiphyseal closure
-increases lean body mass, reduces fat
-decreases levels of HDL cholesterol
-stimulates secretory proteins in liver and induces enzymes involved in drug
metabolism
-stimulates sebaceous glands (acne) and hair follicles
-psychological and behavioral effects

Question 10

Describe the feedback control in androgen production. *hint: ___–>GnRH–>____–>LH, FSH–>testes–>___ (inhibit)& ___(inhibit/stimulate)

Answer 10

Describe the feedback control in androgen production. *hint: hypothalamus releases GnRH–>anterior pituitary releases LH, FSH–>testes: Sertoli cells release inhibin (inhibit anterior pituitary)& Leydig cells release testosterone (inhibit/stimulate: anterior pituitary, inhibit: hypothalamus)

Question 11

Androgen insensitivity syndrome is characterized by patients having X/Y male ____ but female ____. They had normal to high levels of estrogen and testosterone, are infertile, 1/60,000 frequency. Mutations are in the ____ receptor (__-linked gene) which typically results in partial loss of function.

Answer 11

Androgen insensitivity syndrome is characterized by patients having X/Y male genotype but female phenotype. They had normal to high levels of estrogen and testosterone, are infertile, 1/60,000 frequency. Mutations are in the androgen receptor (X-linked gene) which typically results in partial loss of function.

Question 12

According to classification by the IAAF regulations, androgen insensitivity syndrome falls under which category?

• conditions that give no advantage
• conditions that may give some advantage, but acceptable

Answer 12

According to classification by the IAAF regulations, androgen insensitivity syndrome falls under which category?

• conditions that give no advantage: androgen insensitivity syndrome, gonadal dysgenesis, turner’s syndrome
• conditions that may give some advantage, but acceptable: congenital adrenal hyperplasia, androgen producing tumors, anovulatory androgen excess (polycystic ovary syndrome)

Question 13

Spinal bulbar muscular atrophy (Kennedy’s disease) results in muscle cramps and progressive weakness due to degeneration of motor neurons in the ____ and ____. Age of onset varies from ____ to ____, but most commonly develops in middle age. The biochemical mechanism is related to binding of ____ to testosterone, which causes ____in the nucleus of motor neurons. The length of the expansion determines age of onset (longer=earlier age of onset)

Answer 13

Spinal bulbar muscular atrophy (Kennedy’s disease) results in muscle cramps and progressive weakness due to degeneration of motor neurons in the brain stem and spinal cord. Age of onset varies from adolescence to old age, but most commonly develops in middle age. The biochemical mechanism is related to binding of polyQ AR to testosterone, which causes aggregation in the nucleus of motor neurons. The length of the expansion determines age of onset (longer=earlier age of onset)

Question 14

Therapeutic purposes of the androgens (5):

Answer 14

• HRT: hypogonadism, transmen undergoing gender reassignment, loss of testicular function d/t disease or CA, middle age/older men
• Menopause: bone density, muscle mass loss, depression, libido
• endometriosis: use danazol to inhibit FSH and LH to decrease estrogen and cause atrophy of ectopic endometrial tissue
• chronic wasting: HIV, CA patients
• male contraception

Question 15

Body dysmorphic disorder is often seen in pubescent, teen and early 20’s of both ___ (anorexia, bulimia) and ___ (steroids).

Answer 15

Body dysmorphic disorder is often seen in pubescent, teen and early 20’s of both females (anorexia, bulimia) and males (steroids).

Question 16

Modulating androgen production (3):

Answer 16

• GnRH hormone analogs
• 5 α-reductase inhibitors
• Androgen Receptor antagonists

Question 17

Dutasteride (block both types), Finasteride (block type 2)

5α-reductase inhibitors block production of _____. They are used in treatment of (3):

Answer 17

5α-reductase inhibitors block production of dihydrotestosterone. They are used in treatment of (3):

• prostate CA
• BPH
• androgenetic alopecia (finasteride ONLY)

Question 18

Side effects of 5α-reductase inhibitors (3):

Answer 18

loss of libido, ED, gynecomastia

Question 19

Cyproterone, Spironolactone

Androgen receptor antagonists (steroidal) prevent binding of ____ & ____ to AR. They are used in treatment of (8):

Answer 19

Androgen receptor antagonists (steroidal) prevent binding of testosterone & dihydrotestosterone to AR. They are used in treatment of (8):

• prostate CA
• BPH
• androgenetic alopecia
• female hirsutism
• priaprism
• hypersexuality
• precocious puberty
• male to female transgender

Question 20

Side effects of steroidal androgen receptor antagonists (5):

Answer 20

liver toxicity, adrenal suppression, depressive mood changes, gynecomastia, ED

Question 21

Flutamide, Nilutamide, Bicalutamide

Androgen receptor antagonists (nonsteroidal) prevent binding of ____ & ____ to AR. They are used in treatment of (2):

Answer 21

Androgen receptor antagonists (non steroidal) prevent binding of testosterone & dihydrotestosterone to AR. They are used in treatment of (2):

• prostate CA
• female hirsutism

Question 22

Side effects of nonsteroidal androgen receptor antagonists (3):

Answer 22

Gynecomastia, mild liver damage, GI effects (bicalutamide better than flutamide)