Androgens

What characterizes male phenotype in livestock is characterized by what?

Chromosomal composition

Functionally and structurally competent testes

Adequate amounts of tonic androgen production

Appropriate external and internal genitalia

Hormones responsible for the male phenotype

GnRH

LH

FS

Testosterone

DHT

Anti-Mullerian hormone (AMH)

Inhibin/Activin

Estradiol

What hormone controls the Sertoli cells and what does it do?

FSH & Testosterone: initiate spermatogenesis

secrete inhibin

FSH: binds G-protein coupled receptor that causes synthesis of inhibin and androgen binding protein (ABP) which delivers androgens to spermatocytes and spermatids in seminiferous tubules

FSH stimulates proliferation and differentiation of Sertoli cells

What hormone controls the Leydig cells and what does it do?

LH: causes synthesis of StAR (steroidogenic acute regulatory protein) which initiates steroidogenesis in mitochondria

Testosterone production

Paracrine interactions with Sertoli support spermatogenesis

Main functions of androgens in males?

Development and maintenance of male reproduction

Anabolic skeletal muscle effects

Where does cleavage of cholesterol to testosterone occur?

Leydig cells

What are the 3 pathways for testosterone to interact at target tissues?

As testosterone: muscle

5α-reductase converts to DHT: skin and prostate (amplification pathway)

Aromatase converts to E2: Bone and brain (diversification pathway)

Where does aromatization of testosterone to estradiol occur?

Adipose

Testis (Sertoli and Leydig)

Brain: feedback to decrease GnRH secretion

Bone: helps close epiphyseal plate

Breast

Liver

Blood Vessels

How much testosterone is in free circulation? What is testosterone bound to?

0.5-3% is free in circulation

Most is bound to albumin but some bound to steroid hormone binding globulin (SHBG) from the liver

How are androgens degraded?

Cytochrome p450 adds a hydroxyl group

Conjugated with glucuronic acid or sulfate and released in urine or bile.

What are the 3 possible levels for negative feedback on GNRH?

Kisspeptin neurons

GnRH neurons

Pituitary gonadotrophs

How does kisspeptin regulation work?

Contain both androgen and estrogen receptors

Binding causes repression which leads to lower GnRH

What are inhibin's? What do they do?

FSH causes Sertoli cells to produce inhibin

Inhibin-B inhibits FSH secretion from pituitary

2 forms with different beta subunits

What are activins? What do they do?

Stimulate secretion of FSH

Inhibin binds to the type II receptor blocking activin (TGFβ strengthens bonding of inhibin)

Important in testes development and spermatogenesis

What is the role of prolactin in males?

Half the level of females

High levels of PRL works to inhibit GnRH secretion, thus LH and FSH, and ultimately testosterone

What does the androgen receptor like?

Widely expressed but sensitivity varies in non-reproductive tissues

ON X CHROMOSOME

Nuclear receptor that influences transcription

What is testosterone responsible for?

Differentiation of male internal genitalia

Differentiation & maintenance of male secondary sex characteristics

Skeletal and muscle growth

Libido

What is DHT responsible for?

Differentiation of male external genitalia

Prostatic growth

What is estrogen responsible for?

Bone mineralization; epiphyseal closure

Sexual differentiation of the brain

Vascular system: protection from atherosclerosis

Provides negative feedback inhibition on GnRH secretion

What on the Y chromosome conveys male development?

The SRY gene is detected at 42 days

SOX9 leads to development of testes

inhibited by WNT4/β-catenin and FOXL2

Activated by FGF9, SRY, and PGDS

What is gonadal sex?

Morphology of the gonads and the hormones they produce

What is phenotypic sex?

Appearance of the external genitalia as well as secondary sex characteristics

What is somatic sex?

Difference in the structures of internal sex organs

What does Anti-mullerian hormone (AMH) do?

It is secreted by the Sertoli cells to bring about regression of the mullerian ducts

Leydig cells secrete testosterone to stabalize Wolffian duct

What marks the onset of puberty?

Increase in pulsatile GnRH

GnRH and Glut. neurons are restrained by gamma-aminobutyric acid (GABA) but KNDy overcome to secrete GnRH

How long does it take sperm to mature?

74 days

How many sperm are produced?

120 million sperm/day

Ejaculate contains 100 million (2.5ml-3.5ml)

What are the 3 phases of spermatogenesis?

Mitotic phase involving proliferation

Meiotic phase yielding

primary spermatocytes-> secondary spermatocytes-> spermatids

Transformation into mature spermatozoa

Maturation of the spermatid

Loss of cytoplasm

Development of acrosomal head

Organization of mitochondria on midpiece

Elaboration of flagellar tail

What do androgens do for prostate?

Cause it to grow