Lecture 19: Reproduction 3 (Hormonal Control)

Question 1

What is GnRH?

Answer 1

-Decapeptides (10 AA) present in all vertebrates
-3 major types of GnRH (1 in mammals)
-Released in a pulsatile manner in the median eminence
-Travel via the portal blood system to the anterior pituitary
-In the hypothalamus, GnRH neurons receive info about internal and external status

Question 2

What are GnRH receptors?

Answer 2

-GnRH receptors= G-protien coupled receptors
-Most species posses at least 2 types of receptors
-Upon binding, can stimulate both Gaq and Gas (talked about in endocrine)
-In the pituitary, leads to the synthesis and relate of gonadotropin (LH and FSH)
-GnRHR’s are also present in other tissues such as ovary, prostate and placenta

Question 3

What is the role of LH and FSH?

Answer 3

-Glycoprotein hormones composed of 2 subunits:
Common a SU + Specific B SU (LHB and FSHB)
-In most mammals: produced by the same pituitary cells (gonadotropes)
-Differential regulation based on GnRH pulse frequency
-B SU is the limiting factor (unique for each hormone)
-Control at the gene transcription level
-Secreted = stored in vesicles until signal (GnRH) is received

Question 4

What are LH and FSH receptors?

Answer 4

LH receptors:
-G-protein couple receptor
-Activates Gas= increase in cAMP
-Binds both LH and hCG (placental source of gonadatropin to be converted in lecture on implantation)

FSH receptor:
-Also a G-protein coupled receptors signalling via Gas

Question 5

What is the difference between inhibin and activin?

Answer 5

-Glycoproteins composed of 2 subunits
-Inhibin produced by Sertoli cells in males and granulosa cells in females
-Inhibin inhibits FSH
-Activin stimulates FSH
-Present in follicular fluid
-Produced by pituitary gonadotropes (possible autocrine paracrine effect)
-Mainly act in conjunction with GnRH

Question 6

What are gonadal (sex) steroids?

Answer 6

-Derived from stepwise conversion of cholesterol (lipophilic with nuclear/ intracellular receptor)
-Type of steroid depends on the presence of specific enzyme substrate in the cell

Order Key enzymes
-Pregnenolone. -Cytochrome p450
-Progesterone. -17a hyroxylase SCC
-Testosterone -5a reductase
-Estradiol-17B -5a-Dihydrotestosterone (DHT)

Question 7

What is so important about Estradiol-17B?

Answer 7

-A potent steroid
-A ring critical to estradiol, differs from testosterone which is weaker than estradiol
-Note that phenolic ‘A’ ring distinguishes a very potent estrogen from a moderate androgen (testosterone)

Question 8

What are sex steroid receptors?

Answer 8

-Receptors= NHR = effect on gene transcription
-Recently: non-genomic rapid effects discovered
-Since steroids diffuse in virtually any cell of the body and receptors are widely distributed: multiple target organs
-Testosterone uses the androgen receptor
-Estrogens have 2 receptor types ERa and ERB (tends to have opposite effects)
-Receptors require coactivators/regulatory molecules to mediate their actions on target gene promoters

Question 9

What are the differences between ERa and ERB?

Answer 9

-location/presence (cell type)
-ERa stimulates transcription while ERB inhibits it
-Effects of drugs will depend on ability to bind and activate ERa or ERB

Question 10

What is kisspeptin and why is it the key link?

Answer 10

-Controlling GnRH
-Its receptor GPR54 has been localized in the hypothalamus on GnRH neurons

-GnRH neurons don’t express ER’s but kisspeptine neurons do= missing link