Opioidergic modulation of N-methyl-D,L-aspartic-acid-stimulated LH release in young adult but not older male mice.
Among the neuromodulators of the GnRH neuronal system are the endogenous opioid peptides and the excitatory amino acids. Although the opioid antagonist naloxone (NAL) induces LH secretion in many species, there are no reports of an effect of NAL on LH release in mice. Our previous studies demonstrated that the excitatory amino acid analog N-methyl-D,L-aspartic acid (NMA) stimulates LH release in mice and suggested that NMA-induced LH release is mediated via afferents to GnRH neurons. In the current study, the role of the endogenous opioid system in the regulation of LH release in adult male mice was assessed by testing whether this system is a component of the NMA-stimulated LH response. NAL, its quaternary derivative NAL methiodide (which remains outside of the blood-brain barrier) and saline (SAL) were administered alone and in combination with NMA via intravenous catheters. Although neither opioid antagonist stimulated LH release when administered alone, each significantly potentiated the LH response to NMA in young adult (10- to 14-week-old) male mice (p < 0.01) but not in older (10- to 16-month-old) male mice. The equivalent action of the two ipioid blockers suggested an action outside of the blood-brain barrier. To determine whether opioid blockade altered pituitary sensitivity to GnRH, a dose response for exogenously administered GnRH was first determined, and low and high doses of GnRH were tested in combination with NAL or SAL. Neither treatment was effective in altering the LH response to GnRH, indicating that the action of the opioid antagonists was at a suprapituitary location. (ABSTRACT TRUNCATED AT 250 WORDS)
Miller
G M
GM
Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029.
Gibson
M J
MJ
D000375:Aging / Q000378:metabolism*; D000818:Animals; D006328:Cardiac Catheterization; D004305:Dose-Response Relationship, Drug; D004723:Endorphins / Q000502:physiology*; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology; D007986:Luteinizing Hormone / Q000378:metabolism*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D016202:N-Methylaspartate / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D011863:Radioimmunoassay
D004723:Endorphins; D007987:Gonadotropin-Releasing Hormone; D009270:Naloxone; D016202:N-Methylaspartate; D007986:Luteinizing Hormone