Dissecting autocrine effects on pulsatile release of gonadotropin-releasing hormone in cultured rat hypothalamic tissue.
The control of reproductive function is manifested centrally through the control of hypothalamic release of gonadotropin-releasing hormone (GnRH) in episodic events or pulses. For GnRH release to occur in pulses, GnRH neurons must coordinate release events periodically to elicit a bolus of GnRH. We used a perifusion culture system to examine the release of GnRH from both intact hypothalami and enzymatically dispersed hypothalamic cells after challenge with GnRH analogs to evaluate the role of anatomical neuronal connections on autocrine/paracrine signals by GnRH on GnRH neurons. The potent GnRH agonist des-Gly(10)-D-Ala(6)-GnRH N-ethylamide, potent GnRH antagonists D-Phe(2)-D-Ala(6)-GnRH and D-Phe(2,6)-Pro(3)-GnRH or vehicle were infused, whereas GnRH release from hypothalamic tissue and cells were measured. PULSAR analysis of GnRH release profiles was conducted to evaluate parameters of pulsatile GnRH release. Infusion of the GnRH agonist resulted in a decrease in mean GnRH (P < 0.001), pulse nadir (P < 0.01), and pulse frequency (P < 0.05) but no effect on pulse amplitude. Infusion of GnRH antagonists resulted in an increase in mean GnRH (P < 0.001), pulse nadir (P < 0.05), and pulse frequency (P < 0.05) and in GnRH pulse amplitude only in dispersed cells (P < 0.05). These results are consistent with the hypothesis that GnRH inhibits endogenous GnRH release by an ultrashort-loop feedback mechanism and that treatment of hypothalamic tissue or cells with GnRH agonist inhibits ultrashort-loop feedback, whereas treatment with antagonists disrupts normal feedback to GnRH neurons and elicits an increased GnRH signal.
Woller
Michael J
MJ
Biological Sciences, University of Wisconsin-Whitewater, Whitewater, Wisconsin 53190, USA. wollerm@uww.edu
Meyer
Scott
S
Ada-Nguema
Aude
A
Waechter-Brulla
Daryle
D
D000818:Animals; D019898:Autocrine Communication / Q000187:drug effects / Q000502:physiology*; D001667:Binding, Competitive; D046508:Culture Techniques / Q000379:methods; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007031:Hypothalamus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009415:Nerve Net / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010507:Periodicity; D051381:Rats; D017207:Rats, Sprague-Dawley
D007987:Gonadotropin-Releasing Hormone