Biology of Reproduction Summers

text: Human Reproductive Biology2nd Edition - Richard E. Jones & Kristin H. Lopez,: Read pages 97-121 for this lecture acronyms    end

XI. Gonadal Axis regulation 			back to X. Adult Male

	A. GnRH (pulsatile) ® LH (pulsatile) ® T - - - ® E2


		1. GnRH stimulates the release of both LH and FSH

			a. pulsatile GnRH release necessary
				   for gonadotropin secretion


		2. pulsatility maintains [GnRH-R]

		3. autopriming: LH/FSH release 4-6x higher
			   on 2nd dose (pulse) of GnRH


	B. mechanism of pulsatile GnRH release

		1. GnRH neurons have intrinsic oscillatory capacity

		
			a. may be enhanced or paced by extra-ARC transmitters

				i. NE, NPY, GABA pulse synchronously with GnRH

					(1) NPY + GABA are transmitters used 
					   for timing by SCN


		2. GnRH  2nd messengers are Gs ® AC ® cAMP   or
                                    IP3 ® Ca++ ® calmodulin


		3. autocrine  +feedback control

			a. pacemaker ® V gated Ca++ ®+ exocytosis ®+ GnRH 


			b. GnRH ®+ GnRH-R (autoreceptors) ®+ IP3/Ca++


				i. Ca++ ®+ NOS ®+ NO ®+ (more) GnRH

			c. ultrashort  negfeedback inhibits spontaneous pulsatility
				during 2nd phase (habituation of autoreceptor action?)

				
	C. T or E2/P feed back to regulate GnRH and LH levels

		1. carried by binding proteins (SBP) in the blood (for Long-Loop fb)


		2. manner of feedback determines manner of release

			a. + vs -
				   modified by activin, inhibin, leptin, galanin, b-endorphin


	D. Endocrine Positive Feedback
	
		1. in females  E2 is monitored by anterior hypothalamus (APS)
		
		
		2. at E2 & daytime thresholds GnRH surge stimulated
		
			a. circadian rhythm timed by SCN
			
				i. regulated by AVP and VIP
		
		
		3. E2 threshold adds Glu to NE stimulation
		
			a. Glu stimulates VIP in SCN too
		

	E. Inhibin/Activin

		1. small polypeptides

		
		2. made in Sertoli and Granulosa cells
		
			a. also found in Antral fluid


		3. feeds back to regulate FSH levels

			a. selectively inhibits (inhibin)
				   or stimulates (activin) FSH


	F. Leptin

		1. produced by adipose (fat) cells


		2. stimulates GnRH by binding to  ob/obb-R


	G. galanin (Gal)

		1. colocalized in GnRH neurons,
			   and stimulates GnRH release (with NPY) 


		2. released with GnRH,
			   also stimulates LH  (but not FSH)


	H. Androgen Target Cells

		1. Secondary Sex Characteristics
		   (facial hair, rooster comb, phallus development)

				5a-reductase
			a. T --------® 5a-DHT

				i. intracellular conversion at target tissue


			b. DHT binds to cytoplasmic/nuclear receptors (A-R)


		2. muscle has no 5a-reductase

			a. although A-R have a higher affinity for 5a-DHT,
			   T may bind when concentrations are high enough


		3. Brain (and other adipose tissue)

				aromatase
			a. T -------® E2

				i. bind to E-R