Duration of a full cycle of spermatogenesis; “spermatogenic wave”:
64 days
Inhibin inhibits?
anterior pituitary
FSH and LH
Testosterone inhibits:
Hypothalamus AND Anterior pituitary
FSH/LH and GnRH
LH acts on _______ cells.
Leydig
FSH acts on _______ cells.
Sertoli
Inhibin comes from _________ cells.
Sertoli
Numerical relationship between sperm production and Sertoli cell number:
linear
Numerical relationship between sperm production and Leydig cell number:
Why?
Linear
Testosterone helps stimulate Sertoli cells
What would decreased testosterone levels do to GrRH?
increase
**less negative feedback
Physical musculoskeletal effects of low testosterone:
increased abdominal fat
decreased muscle mass
Finasteride
5-a-reductase inhibitor
Tx for: baldness, prostate CA
What does 5-a-reductase do?
converts testosterone to DHT (more potent form)
Testosterone targets:
Muscle
Seminal Vesicle
Epidydimis
Bone
8 mg of daily testosterone in males produced in which two places?
Leydig cells (Testes) — 95%
adrenals — 5%
Androgen receptor location and site of action:
cytoplasm — binding of androgens
nuclear transcription factors
Anabolic effects of androgens (3):
- muscle building
- bone growth – closure of epiphysis
- Na/H2O retention
Read slide….
20
Testosterone analog
hormone replacement
hepatotoxic
Methyl testosterone
DHT derivative
anabolic steroid
Oxandrolone
What happens to gonads with exogenous testosterone use:
shrink
**inhibits hypothalamic pituitary axis –> no stimulation of androgen receptors
Read slide…
28
Non-steroidal
Pure steroid receptor antagonists
Flutamide
Bicalutamide
Difference between “pulsatile” and “continuous” exposure to GnRH analogs:
“pulsatile” is stimulatory
“continuous” is inhibitory
GnRH analog (recombinant human form)
pulsatile for 3-6 mo for male infertility
Gonadorelin
GnRH analog (synthetic)
continuous for chemical castration in prostate CA
Leuprolide
**initial surge in Testosterone due to hypersecretion of LH and FSH
followed by suppression (~10 days after) due to desensitization of GnRH receptors
GnRH recepto blocker
prostate CA
BPH
Degarelix
GnRH receptor blocker
blocks premature LH surge in females
Ganirelix
Cetrorelix
Major difference between GnRH agonists and antagonists
antagonists don’t have initial hypersecretory phase
5-a-reductase inhibitor
BPH
prostate CA
baldness
Finasteride
NT for parasympathetic nerve responsible for erection
NO
NO second messenger?
Guanalyl cyclase –> increases intracellular cGMP
cGMP promotes arteriole dilation
What degrades cGMP in vascular SM to end an erection?
Phosphodiesterase 5
Phosphodiesterase 5 inhibitor to facilitate erection:
Sildenafil — Viagra
Tadalafil — cialis — longer duration
What not to use with PDE-5 blockers?
alpha-blocker!!!
double whammy on vasodilation –> hypotension