In vivo and in vitro studies on the opioidergic control of the secretion of gonadotrophin-releasing hormone and luteinizing hormone in sexually immature and adult male rats.
In vivo and in vitro methods have been used to compare the effects of opioid receptor blockade on the functional activity of the hypothalamo-pituitary-gonadal axis in adult (200 g) and sexually immature (50 g) male rats. In the adult, a single injection of the mu-receptor antagonist, naloxone (500 micrograms/100 g body weight, s.c.), produced hypersecretions of luteinizing hormone (LH) and testosterone. Maximal serum concentrations of the two hormones were attained within 20 and 60 min respectively. In contrast, neither ICI 174864 (100 micrograms/100 g body weight, s.c.) nor MR2266 (150 micrograms/100 g body weight, s.c.), which block delta- and kappa-receptors respectively, stimulated pituitary-gonadal activity; indeed, like the saline vehicle, both tended to depress the serum LH concentration. The injection procedure was sufficient to activate the hypothalamo-pituitary-adrenal axis and, thus, the vehicle-treated controls exhibited significant increases in the plasma adrenocorticotrophin and serum corticosterone concentrations. These effects were enhanced by naloxone (500 micrograms/100 g body weight, s.c.) and by the kappa-opioid receptor (MR2266, 150 micrograms/100 g body weight, s.c.) but not by the delta-opioid receptor antagonist (ICI 174864, 30-100 micrograms/100 g body weight, s.c.). The increases in serum corticosterone and LH concentration induced by naloxone in adult rats were not apparent in the sexually immature (50 g) animals. To the contrary, in the young rats naloxone (250 and 500 micrograms/100 micrograms body weight, s.c.) attenuated, in a dose-dependent manner, the pronounced hypersecretion of corticosterone induced by the vehicle injection. The higher dose of the antagonist (500 micrograms/100 g body weight, s.c.) also overcame the significant reductions in serum LH evident 20 (p less than 0.05) and 40 (p less than 0.01) min after the saline injection but the lower dose (250 micrograms/100 g body weight, s.c.) was ineffective in this respect. In vitro, hypothalami from both adult and sexually immature rats responded to the addition of naloxone (10(-8)-10(-6) M) to the incubation medium with significant (p less than 0.01) concentration-dependent increases in the release of gonadotrophin-releasing hormone (GnRH). In contrast, ICI 174864 (10(-7)-10(-6) M) and MR2266 (10(-7)-10(-6) M) had little effect on the secretion of the releasing hormone by hypothalami from rats of either group although, at the highest concentration tested, MR2266 (10(-6) M) precipitated a small increase in GnRH release from hypothalami from adult rats.(ABSTRACT TRUNCATED AT 400 WORDS)
Leposavic
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Department of Pharmacology, Charing Cross and Westminster Medical School, London, UK.
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Buckingham
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D000311:Adrenal Glands / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001575:Benzomorphans / Q000494:pharmacology; D003345:Corticosterone / Q000097:blood / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007986:Luteinizing Hormone / Q000378:metabolism*; D008297:Male; D009270:Naloxone / Q000378:metabolism / Q000494:pharmacology; D009292:Narcotic Antagonists; D010902:Pituitary Gland / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000502:physiology*; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D012741:Sexual Maturation / Q000502:physiology*; D013739:Testosterone / Q000378:metabolism
D001575:Benzomorphans; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D007987:Gonadotropin-Releasing Hormone; D009270:Naloxone; D013739:Testosterone; C027247:MR 2266; D007986:Luteinizing Hormone; D003345:Corticosterone