Analgesic effects of the putative FSH-suppressing gonadal steroid, 3 alpha-hydroxy-4-pregnen-20-one: possible modes of action.
The effects of intracerebroventricular (i.c.v.) administrations of the putative follicle stimulating hormone (FSH) suppressing gonadal steroid, 3 alpha-hydroxy-4-pregnen-20-one (3A4P) on the nociceptive responses of male mice were examined. This allylic steroid elicited significant, dose-dependent (0.001-1.0 micrograms) analgesic responses for 90-150 min after injection. These analgesic effects of 3A4P were stereospecific, the stereoisomer, 3 beta-hydroxy-4-pregnen-20-one (3B4P) failing to affect the nociceptive responses. The analgesic effects of 3A4P were blocked by peripheral administrations of the GABA antagonists, bicuculline and picrotoxin, and reduced by the benzodiazepine antagonist, Ro 15-1788. The exogenous opiate antagonist, naloxone, and the putative endogenous opioid antagonist, Tyr-MIF-1 (Pro-Leu-Gly-amide), also reduced 3A4P-induced analgesia, while i.c.v. administration of 3A4P (0.001 and 0.01 micrograms) itself attenuated the analgesic effects arising from peripheral administrations of opiate receptor agonist, morphine. In addition, the calcium channel antagonists, nifedipine and verapamil, enhanced 3A4P-induced analgesia but had no evident effects on the actions of 3B4P. These results suggest that the central analgesic effects of the FSH-suppressing steroid, 3A4P, arise via benzodiazepine--GABA--opiate mechanisms and calcium channels. These findings also suggest possible central modes of action whereby 3A4P may elicit selective suppression of FSH.
Wiebe
J P
JP
Department of Zoology, University of Western Ontario, London, Canada.
Kavaliers
M
M
D004092:20-alpha-Dihydroprogesterone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000698:Analgesia; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D005442:Flumazenil / Q000494:pharmacology; D005640:Follicle Stimulating Hormone / Q000037:antagonists & inhibitors*; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D009270:Naloxone / Q000494:pharmacology; D011374:Progesterone / Q000031:analogs & derivatives*; D012016:Reference Values
D000700:Analgesics; D002121:Calcium Channel Blockers; D004092:20-alpha-Dihydroprogesterone; C052610:3-hydroxypregn-4-en-20-one; D009270:Naloxone; D005442:Flumazenil; D011374:Progesterone; D005640:Follicle Stimulating Hormone; D001640:Bicuculline