Effect of naloxone on the growth hormone response to clonidine in normal women during the mid-luteal phase.
We studied the effect of the opiate antagonist naloxone on the peripheral GH response to the alpha 2-receptor agonist clonidine in eight normally cycling women during the mid-luteal phase. In a randomized, double-blind, cross-over design, each subject received clonidine and naloxone on one occasion and clonidine and placebo on the other. In seven of eight subjects, an attenuation of the GH response was associated with naloxone administration. The maximal GH increment above baseline (delta GHMAX) of 7.8 +/- 2.0 micrograms/L (mean +/- SEM) with placebo was higher than the delta GHMAX of 4.2 +/- 0.9 micrograms/L with naloxone (p = 0.05). Likewise, the area above baseline under the GH level-time curve following clonidine (delta GHAREA) was higher with placebo compared to naloxone (477 +/- 175 micrograms/L x min vs. 228 +/- 62 micrograms/L x min), although this difference was not quite statistically significant (p = 0.09). As expected, with placebo the increase in GH following clonidine was statistically significant by repeated measures analysis of variance (p = 0.001). The smaller increase in GH levels when naloxone was given was not significant. Both delta GHMAX and delta GHAREA values were significantly positively correlated with estradiol levels when placebo was given, but not when naloxone was given. GHRH was not detectable following clonidine administration under either the placebo or the naloxone conditions. Our data support the hypothesis that estrogen enhances the response of GH to provocative stimuli in women, at least in part by increasing endogenous opioid tone in the hypothalamus.
Phipps
W R
WR
Department of Obstetrics and Gynecology, University of Minnesota Medical School, Minneapolis 55455.
Campbell
B F
BF
Pescovitz
O H
OH
D000328:Adult; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects; D003000:Clonidine; D004958:Estradiol / Q000097:blood; D005260:Female; D013006:Growth Hormone / Q000097:blood*; D006801:Humans; D007031:Hypothalamus / Q000187:drug effects; D008183:Luteal Phase / Q000187:drug effects*; D009270:Naloxone / Q000494:pharmacology*; D011374:Progesterone / Q000097:blood; D011957:Receptors, Opioid / Q000187:drug effects
D011957:Receptors, Opioid; D009270:Naloxone; D011374:Progesterone; D004958:Estradiol; D013006:Growth Hormone; D003000:Clonidine