Normal Male Reproduction (Richter)

Richter

Spermatid to spermatozoa

Spermiogenesis

Blood testis barrier is formed by ____ cells and protects the ____ cells

Sertoli cells

germ cells

The __ chromosome determines sex

Y

XXY, male, low testosterone, reduced fertility/infertility

Klinefelter syndrome

X0, female, results from a missing or incomplete sex chromosome.

Symptoms include short stature, delayed puberty, infertility, heart defects, and certain learning disabilities.

Treatment involves hormone therapy. Fertility treatment may be necessary for women who want to become pregnant.

Turner syndrome

Gonads are indifferent up to __ weeks of gestation. Gene products of the SRY (sex-determining region of the Y chromosome) locus drive the development of male gonads.

5

Sertoli cells begin to secrete ___________ leading to regression of the ______ duct (the precursor of female reproductive structures)

Anti-Mullerian Hormone (AMH)

Mullerian

Testosterone (converted to dihydrotestosterone) promotes growth of _____ ducts into male reproductive structures (epididymis, vas deferens, etc.)

Wolffian

In absence of AMH, Mullerian ducts develop into female reproductive structures (no _______ required)

hormone 

In females Wolffian ducts regress at __ weeks due to lack of testosterone

10

In females, after __ weeks, X chromosome is activated and initiates oogenesis

9

Sexual differentiation slide 

Sertoli cell female counterpart

Granulosa cells

Leydig cell female counterpart

Theca cells

maintains Sertoli cell function required for initiation and maintenance of spermatogenesis.

FSH 

_____ cells produce androgen binding protein (ABP) which binds testosterone and enables high concentrations of testosterone to accumulate in the testis.

Sertoli

Responsible for testosterone synthesis.

Leydig cells

Leydig cells have high expression levels of _________, one of the rate-limiting enzymes in testosterone synthesis.

17-beta-hydroxysteroid dehydrogenase

stimulates testosterone production in Leydig cells

LH

Both testosterone (and dihydrotestosterone or DHT produced in peripheral tissues by 5-alpha-reductase) are necessary for _________ and are responsible for all aspects of male sex characteristics

spermatogenesis

Testosterone production 

Cholesterol side chain cleavage enzyme is in the inner mitochondrial membrane 

Increase cholesterol to inner mitochondrial membrane, increase

steroid synthesis because cholesterol side chain enzyme can access more substate

DHT has a _____ half-life compared to testosterone but is _____ potent

Short

More

Testosterone → DHT 

5 alpha reductases (periphery) 

Androstenedione → testosterone

17 beta - HSD (Leydig cells)

Testosterone binds to _________ synthesized by Sertoli cells, which allows high accumulation of testosterone in testis.

Androgen Binding Protein

Testosterone is transported in blood bound to ______ or _______

SHBG (Sex hormone-binding globulin; similar to ABP) or albumin.

Androgen receptor is a _______ receptor

Nuclear

Testosterone can be converted in target tissues to dihydrotestosterone (DHT; by 5-α reductase) or _______ (by aromatase).

estradiol

Gonadotropic hormones FSH and LH are released from the 

anterior pituitary 

LH couples to G_ receptors

Gs leading to adenylyl cyclase, cAMP, PKA, transcription of enzymes that synthesize tessosterone

LH binds to the Leydig-cell’s LH-receptor, a seven transmembrane receptor, which couples to G_ thereby increasing _______ production to stimulate testosterone synthesis.

Gs

cAMP

cAMP/PKA-signaling induces _______, which promotes transport of cholesterol to the side-chain-cleavage enzyme (SCC) located in the inner mitochondrial membrane, which is a rate-limiting step in testosterone synthesis.

StAR (steroidogenic acute regulatory protein)

promotes transport of cholesterol to the side-chain-cleavage enzyme (SCC) located in the inner mitochondrial membrane

StAR (steroidogenic acute regulatory protein)

FSH stimulates a seven transmembrane receptor coupled to G_ and _____ in the Sertoli cell, to stimulate the expression of aromatase, ABP (androgen binding protein) and growth factors necessary for spermatogenesis and Sertoli cell function.

Gs and cAMP

Testosterone moves through the basal lamina into Sertoli cells where it has two fates: one, to exit into the __________ where it binds to androgen binding protein (ABP) and regulates spermatogenesis, or two, to be converted to estradiol 17-beta by _______.

seminiferous tubules lumen 

aromatase 

the half-life of LH is __ min, while that of FSH is _ h.

30; 2

______ release of GnRH from hypothalamic neurons promotes LH and FSH expression and release in the anterior pituitary.

Pulsatile

GnRH is a peptide acting on GnRH receptors that are coupled to G_/___ signaling.

Gq/PLC

How GnRH stimulates LH and FSH production and release 

In males, FSH stimulates the expression of _______ in Sertoli cells which blocks expression/secretion of FSH in pituitary gonadotrophs

Inhibin B

LH increases testosterone production. Circulating testosterone, blocks _____ release from the hypothalamus as well as LH expression in the pituitary.

GnRH

Inhibin decreases ____, testosterone decreases ____ and ____

FSH 

FSH and LH 

•In utero development of male reproductive tract

•Increases muscle mass at puberty

•Regulates liver lipoprotein profiles

•Promotes male fat distribution

•Thickens vocal chords

Testosterone predominant

•Growth of penis and scrotum

•Growth of facial hair

•Increase prostate growth (prostate hyperplasia)

•Male pattern baldness

DHT predominant

•Growth and development of male genitalia and reproductive structures (vas deferens, epididymis, glands, etc.)

•Sperm production

•Libido

“Survival of the species”

Testosterone and DHT 

Testosterone is also converted to _____ in peripheral tissues, especially adipose tissue, bone or brain

Estrodiol 

______ tissue supplies much of the estrogen found in males.

Adipose

Sperm production

Feedback suppression of gonadotropin secretion

imprint male pattern of gonadotropins, sex drive, behavior

Function of estradiol in males

Function of Testosterone 

DHT

Estradiol 

Age related changes in male gonadal function

Leydig cells are very active in both fetal and neonatal life and ______ is necessary for the differentiation of male reproductive structures.

testosterone

Age ___-____: GnRH secretion is low; testes are quiescent; androgen levels low.

1-10

Age ___-___: pulsatile GnRH secretion begins; LH and FSH are released in higher concentrations.

10-12

Age ____-___: puberty begins; testosterone levels rise and secondary sex characteristics begin to develop.

12-14

Age ___-___: testosterone levels reach maximum.

18-20

Age __ and beyond: Generally, testosterone levels decline approximately 10% per decade.

40

Male _____ may be maintained into the 7th (and 8th) decade of life due to presence of testosterone

fertility

The period of androgen deficiency is called 

Andropause