male repro endocrinology

Question 1

Define the role of Sertoli cells and Leydig cells during development

Answer 1

Leydig cells produce testosterone (in response to LH) which stimulates growth/differentiation of wolffian ducts. Sertoli cells produc AMH aka MIF which causes apoptosis of mullerian ducts. Development of testis is unilateral (requires T from same side) whereas external genitalia develop from systemic T

Question 2

What is the default pathway for sex development

Answer 2

female- In the absence of testosterone Wolffian ducts involute. Without AMH Mullerian ducts differentiate. Development of Female ducts and external gentalia is independent of gonadal hormones. If no gonads, female format results

Question 3

Functions of Leydig cells

Answer 3

Synthesis of 95% of testosterone. Required for spermatogenesis. Also synthesize StAR and sterol carrier proteins (transport cholesterol and stimulate steroidogenesis). Respond to LH through G protein

Question 4

Where is testosterone converted to estrogen

Answer 4

sertoli cells- androgens from leydig cells go to sertoli cells and are aromatized in response to FSH.

Question 5

What forms the blood sperm barrier

Answer 5

Tight junctions btw sertoli cells. Important to prevent immune attack of spermatozoa.

Question 6

Functions of sertoli cells

Answer 6

Form blood testis barrier (tight junctions), Nuture developing sperm (spermatogenesis), Secrete Androgen Binding Protein (APB- maintains high conc of T locally), Convert Androgens to Estrogen using Aromatase, Secrete Inhibin and other growth factors, Respond to FSH through a GPCR

Question 7

Cross talk btw Leydig and sertoli cells

Answer 7

Leydig produces androgen (LH stimulation). Androgens go to sertoli cells. Sertoli cells convert androgens to estrogens (FSH stimulation). FSH also stimulates release of inhibin and other factors from Sertoli cells which act as growth factors for Leydig cells. T from Leydig cells increases ABP production from Sertoli cells

Question 8

Inhibins

Answer 8

Released from sertoli cells in response to FSH and act locally as growth factors for Leydig cells.

Question 9

describe hypothalamic-pituitary- testes negative feedback

Answer 9

Androgens inhibit release of GnRH. Androgens (and estrogen) inhibit FSH and LH release from pituitary. Inhibin suppresses FSH production

Question 10

How would exogenous androgens affect the H-P-gonads loop in males vs females

Answer 10

Exogenous androgens shut down endogenous production by negative feedback. Males: testicular atrophy. Females: abnormal cycles/amenorrhea, virilization

Question 11

What happens to LH and FSH levels during menopause, aging males

Answer 11

Menopause: Increase due to loss of feedback inhibition by estrogens. Males aging: increase but less so.

Question 12

Sertoli cell only syndrome

Answer 12

Normal LH and T,FSH increased. Decreased spermatogenesis causes decreased production of inhibin and this leads to reciprocal elevation in FSH.

Question 13

List actions of androgens in male

Answer 13

acne, male pattern baldness, enlargement of larynx and thickening/lengthening ov vocal cords, bone growth (also requires estradiol), cardiac risk (fat deposition), erythropoiesis, libido, aggression, sex differentiation of brain in males

Question 14

List actions of androgens in male developmental

Answer 14

Differentiation and development of male internal and external genitalia (T, DHT), Initiation and maintenance of Spermatogenesis (T,DHT, E),
Development and maintenance of 2nd sex characteristics : Growth of external genitalia (T, DHT), Male pattern of hair growth (DHT), Sebaceous gland secretions (DHT), Inhibition of breast growth (T), Libido (T, E, DHT), Stimulation of Androgen binding protein synthesis (T), Muscle growth, strength, Bone growth(T and E)Differentiation and development of male internal and external genitalia (T, DHT), Initiation and maintenance of Spermatogenesis (T,DHT, E),
Development and maintenance of 2nd sex characteristics : Growth of external genitalia (T, DHT), Male pattern of hair growth (DHT), Sebaceous gland secretions (DHT), Inhibition of breast growth (T), Libido (T, E, DHT), Stimulation of Androgen binding protein synthesis (T), Muscle growth, strength, Bone growth(T and E)

Question 15

Pubertal vs prepubertal FSH and LH

Answer 15

Prepubertal: FSH > LH. Pubertal: LH > FSH, this is because GnRH preferentially triggers release of LH in adult male. Possibly due to elevated inhibin release from mature testes

Question 16

Describe pubertal changes in males

Answer 16

adrenarche (8-10 yrs). Gonadotropins begin increasing (8-10yrs). Testicular size increases (8-10yrs). >3ml is onset of puberty. Testosterone starts increasing (around 12 yrs). Pubic hair (12 yrs), penile growth (13 yrs), sperm production and growth spurt (starts around 13 yrs). Growth hormone increases

Question 17

Androgens and growth

Answer 17

Anabolic effects of androgens cause: Growth of somatic tissue, Linear body growth (long bones), Nitrogen retention, protein synthesis, Muscle development.

Question 18

How does GH/ IGF-1 play a role in male puberty

Answer 18

GH/IGF-1 stimulate gonadal functional. IGH-1 stimulates GnRH secretion. Testosterone and estrogen stimulate GH secretion and growth. As T and E decline with age, GH and IGF-1 decline so loss of bone and muscle occurs, plus a gain in fat.

Question 19

define the roles of Growth hormone (GH) and sex steroids in bone growth

Answer 19

Estrogen from T promotes growth and epiphyseal plate closure. Non aromatizable T analogs do not stimulate growth in males. Prenatal growth depends on IGFs and insulin, not GH or estrogen. GH causes balanced growth and ossification of bones. Estrogen causes cartilage growth and ossification.

Question 20

List the actions of estrogen on bone growth

Answer 20

Stimulates bone growth, accelerates bone maturation, promotes epiphyseal closure, limits long-bone growth by narrowing growth window.

Question 21

Prepubertal steroid excess and growth

Answer 21

Prepubertal steroid excess or exogenous sources results in increased growth rate BUT shorter stature

Question 22

nWhat would be the effects of anabolic steroids in a 13 year old?

Answer 22

a

Question 23

nWhy is failure of sexual maturation associated with increased height?

Answer 23

a

Question 24

nCompare the functions of granulosa cells and Sertoli cells: Of Leydig cells and thecal cells.

Answer 24

a

Question 25

nWhy is FSH increased upon castration?

Answer 25

a

Question 26

nWhat would be the phenotype of a genetic male (XY) lacking androgen receptors?

Answer 26

a