Flashcards in Lecture 7: Male Gonadal Physiology Deck (43)
What is the significance of GnRH in males?
Derived from pre-pro-GnRH (protein hormone)
Produced in parvi-cellular hypothalamic neurons
Secreted in hypothalamo-hypophyseal portal system
What is halflife of GnRH? Significance?
Less than 10 minutes
So serum levels are TOO LOW to detect
What is Kallman’s syndrome?
KAL gene mutation
Failure of GnRH neuron precursors to migrate to hypothalamus
What is the structure of GnRH receptor on gonadotrophs/LH and FSH receptors?
What are the characteristics GnRH output in men?
1. There is a circadian (diurnal) rhythm
-24 hour cycle
-controlled by melatonin output by the pineal gland
-greater GnRH action in the early morning
-highest levels of LH and testosterone
2. Also a Pulsatile (ultradian) Rhythm
-pulses every 60-180 minutes
-higher frequency favors LH secretion
-lower frequency favors FSH secretion
-non-physiologic patterns inhibit gonadotropins
-controlled by sex steroid feedback
At a higher frequency GnRH pulse, what is secreted in men?
Same in females
At a lower frequency GnRH pulse, what is secreted in men?
When are the greatest amount of GnRH produced in men?
In the early morning
What is the phenomenon of self-priming?
When GnRH binding sites increase during troughs of GnRH pulses
What is the flare effect?
When excessively frequent of pulsation or continuous GnRH INITIALLY leads to an increase in LH and FSH secretion
After the flare effect, LH and FSH levels become lower
What are the characteristics of LH and FSH?
Consists of alpha and beta-subunitsgranules
Alpha unit is common but Beta unit confers unique characteristic
What are the characteristics of LH in men?
20 minute half=life
-liver enzymes recognize sulfur residues of LH
Acts on LH receptor on the Leydig Cell
Stimulates synthesis of testosterone
Is inhibited by testosterone
What negatively inhibits LH?
What are the characteristics of FSH in men?
2 hour half-life
-sialic acid residues inhibt metabolism
Acts on FSH receptor in Sertoli cell
Inhibited by Inhibin B
What is the purpose of inhibin B in men?
Inhibits FSH production in men
What is the purpose of LH? FSH? IN MEN
To promote testosterone production
To promote spermatogenesis
What does estradiol do in men?
Modifies GnRH response and decreases LH and FSH pulse amplitude
What is the significance of Inhibin B, Activin and Follistatin system in men?
Controls secretion of FSH
Inhibin and follistatin are inhibitory
Activin is stimulatory
What structure in testis is responsible for ENDOcrine function?
What structure in testis is responsible for EXOcrine function?
Dependent on endocrine function
Where do the seminiferous tubules terminate?
At the rete testis which anastomose with seminiferous tubules
Where are spermatozoa stored?
In early pregnancy, what do Leydig cells respond to?
They respond to hCG to produce testosterone
What is the relationship between hCG and Testosterone?
In early pregnancy, hCG, rather than LH, is used to bind to Leydig cells to produce testosterone
What is the rate limiting step of steroid synthesis?
Steroidogenic Acute Regulatory protein
Transports Cholesterol (initial precursor) across inner mitrochondrial membrane 9which is where pregnenolone is made
What are steps of testosterone formation?
1. Steroidogenic Acute Regulatory protein
2. Cytochrome p450 cc
3. 3beta hydroxyl steroid dehydrogenase
4. CYP17 (17 hydroxylase)
5. 17 beta hydroxyl steroid dehydrogenase
What is the mechanism of androgen action?
2 zinc-finger DNA binding domains
1st is involved in DNA binding
2nd is involved in dimerization of androgen receptor
Difference between Testosterone and LH/FSH?
Testosterone = cholesterol/steroid receptor
LH/FSH are peptide hormones so they bind GPCR
Where is testosterone in circulation?
44% bound to SHBG (sex hormone binding globulin)
54% bound to albumin