What are the functions of Leydig cells?
1) Required for spermatogenesis 2) Synthesis of testosterone (95%) 3) Synthesis of Steroidogenic acute regulatory 4) protein (StAR) and sterol-carrier protein (SCP) (Transport cholesterol to mitochondrial side chain cleavage enzyme; Stimulate steroidogenesis) 5) Respond to LH through a G-protein coupled receptor (GPCR)
What are the functions of Sertoli Cells?
1) Form blood testis barrier (tight junctions) 2) Nuture developing sperm 3) Secrete Androgen Binding Protein (APB) 4) Convert Androgens to Estrogen using Aromatase 5) Secrete Inhibin and other growth factors 6) Respond to FSH through a GPCR
What are the three hormones of the Hypothalamic-Pituitary-Testicular axis and what are their targets and results?
GnRH stimulates production of FSH and LH from pituitary LH acts on Leydig cells Increased Testosterone Increased StAR and SCP FSH acts on Sertoli Cells Increased Androgen binding protein (ABP) Increased Aromatase Increased growth factors Increased spermatogenesis Increased inhibin
What are the negative feedback mechanisms in the HPT?
Androgens (Testosterone) inhibit release of GnRH from hypothalamus Androgens (and Estrogen) inhibit LH and FSH release from pituitary Inhibin suppresses FSH production from pituitary gonadotrophs
What are the four primary functions of androgens?
1) Differentiation and development of male internal and external genitalia-T, DHT 2) Initiation and maintenance of Spermatogenesis-T,DHT, E 3) Development and maintenance of 2nd sex characteristics 4) Anabolic functions
What are the secondary sex characteristics in the male?
Growth of external genitalia-T, DHT Male pattern of hair growth-DHT Sebaceous gland secretions-DHT Inhibition of breast growth-T Behavioral responses, Libido-T, E, DHT Negative feedback at hypothalamus, pituitary-E, T Stimulation of Androgen binding protein synthesis-T
What are the results of the anabolic actions of androgens and what receptors and axis do they interact with?
Growth of somatic tissue Linear body growth (long bones) Nitrogen retention, protein synthesis Muscle development Effects mediated by same receptors and molecular mechanisms. Responses are tissue/ organ specific Interactions with Insulin-like growth factor (IGF-1)/ Growth Hormone (GH) axis
How do the GH/IGF-1 and HPT axes interact?
GH/IGF-1 stimulate gonadal functional IGF-1 stimulates GnRH secretion Testosterone and Estrogen stimulate GH secretion and growth
How does testosterone cause bone growth?
T is converted to Estradiol and Stimulates bone growth • Accelerates bone maturation • Promotes epiphyseal closure • Dominant effect is to narrow growth window limiting long-bone growth • Growth ’levels off’ after puberty ( under control of GH/IGF-1 axis) • Prepubertal steroid excess or exogenous sources results in increased growth rate BUT shorter stature
What are some of the consequences of steroid abuse (15 total)?
Infertility-decreased sperm production Gynecomastia- breast development Testicular atrophy Baldness and excessive body hair Short stature Tendon rupture Increase LDL decreased HDL-atherosclerosis High blood pressure Heart attack and stroke Enlargement of left ventricle Liver cancer, pelios hepatis (blood filled cysts) Severe acne, cysts, oily scalp Fluid retention, Kidney failure Psychiatric disturbances-rage, mania, delusions, irritability, insomnia Increased risk of HIV or hepatitis and other infections
Why is failure of sexual maturation associated with increased height?
Sexual maturation leads to the production of higher levels of estradiol (E2) which stimulates bone growth as well as fusing of the epiphyseal plates, which limits total bone length. Lack of maturation inhibits the creation of E2, leading to delayed fusion of the epiphyseal plates.
Why is FSH increased upon castration?
Diminished testosterone production leads to loss of negative feedback to HPT axis
What would be the phenotype of a genetic male (XY) lacking androgen receptors?
What are the overall patterns of gonadotropins, testosterone, testicular size, and phenotypic changes seen during puberty in males?