The role of endogenous opioids in the luteinizing hormone surge in rats: studies with clocinnamox, a long-lasting opioid receptor antagonist.
Endogenous opioid peptides have been demonstrated to regulate luteinizing hormone (LH) secretion in a variety of species. Studies in rodents suggest a role of opioid peptide systems in controlling the timing of the LH surge, which is entrained to the circadian rhythm. The current studies utilize clocinnamox, a novel long-lasting opioid receptor antagonist that is capable of occupying mu-opioid receptors for periods of one week or more, to examine the role of endogenous opioid systems on the LH surge. Administration of clocinnamox [14b-(p-chlorocinamoylamino)-7,8-dihydro-N-cyclopropylmethyl normophineone mesylate]) on the morning of proestrus advanced the LH surge by several hours. Despite the blockade of opioid receptors and analgesia for more than one week, administration of clocinnamox on the evening of diestrus II had no effect on the timing of the LH surge but significantly increased plasma LH levels throughout the day of proestrus. These data suggest that removal of opioid tone is unlikely to be the critical signal controlling the initiation of the LH surge in rodents, although it does appear to be permissive for the surge. Furthermore, the mu-opioid receptor appears to be the receptor involved in the regulation of the LH surge.
Department of Physiology, The University of Michigan Medical Center, Ann Arbor 48109, USA.
P B
PB
Lieberman
J H
JH
Woods
E A
EA
Young
D000818:Animals; D002934:Cinnamates / Q000494:pharmacology*; D002940:Circadian Rhythm; D004971:Estrus; D005260:Female; D007986:Luteinizing Hormone / Q000378:metabolism / Q000502:physiology*; D009022:Morphine Derivatives / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D018847:Opioid Peptides / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors*
D002934:Cinnamates; D009022:Morphine Derivatives; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D017450:Receptors, Opioid, mu; C076806:clocinnamox; D007986:Luteinizing Hormone