Calcitonin gene-related peptide-induced suppression of luteinizing hormone pulses in the rat: the role of endogenous opioid peptides

Calcitonin gene-related peptide (CGRP) is involved in a variety of stress responses in the rat. Central administration of CGRP activates the hypothalamoâpituitaryâadrenal axis resulting in increased corticosterone secretion. We have previously shown that central CGRP suppresses the gonadotrophin...

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Bibliographic Details
Published in:	The Journal of physiology 2005-08, Vol.566 (3), p.921-928
Main Authors:	Bowe, J E, Li, X F, Kinsey-Jones, J S, Paterson, S, Brain, S D, Lightman, S L, O'Byrne, K T
Format:	Article
Language:	eng
Subjects:	Animals Calcitonin Gene-Related Peptide - administration & dosage Dose-Response Relationship, Drug Female Hypothalamo-Hypophyseal System - drug effects Hypothalamo-Hypophyseal System - metabolism Integrative Physiology Luteinizing Hormone - metabolism Pituitary-Adrenal System - drug effects Pituitary-Adrenal System - metabolism Rats Rats, Wistar Receptors, Opioid - classification Receptors, Opioid - metabolism
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Summary:	Calcitonin gene-related peptide (CGRP) is involved in a variety of stress responses in the rat. Central administration of CGRP activates the hypothalamoâpituitaryâadrenal axis resulting in increased corticosterone secretion. We have previously shown that central CGRP suppresses the gonadotrophin-releasing hormone (GnRH) pulse generator, specifically LH pulses. Endogenous opioid peptides (EOPs) have been shown to play an important role in stress-induced suppression of the reproductive axis. The aim of the present study was to test the hypothesis that EOPs mediate CGRP-induced suppression of pulsatile LH secretion. Ovariectomized rats were implanted with intracerebroventricular ( i.c.v. ) and i.v. cannulae. Intravenous administration of the opioid antagonist naloxone (250 Î¼g) completely blocked the suppression of LH pulses induced by 1.5 Î¼g i.c.v. CGRP and significantly attenuated the suppression of pulsatile LH secretion induced by 5 Î¼g i.c.v. CGRP. Furthermore, intravenous administration of naloxone was found to immediately restore normal LH pulse frequency in animals treated 90 min earlier with 1.5 Î¼g i.c.v. CGRP. Co-administration ( i.c.v. ) of CGRP (1.5 Î¼g) with the Î¼ and Îº opioid receptor-specific antagonists naloxone (10 Î¼g) and norbinaltorphimine (5 Î¼g), respectively, blocked the CGRP-induced suppression of LH pulses, whilst i.c.v. co-administration of CGRP (1.5 Î¼g) with the Î´ opioid receptor-specific antagonist naltrindole (5 Î¼g) did not. These data provide evidence that EOPs play a pivotal role in mediating the inhibitory effects of CGRP on pulsatile LH secretion in the rat. They also suggest that the Î¼ and Îº, but not the Î´, opioid receptors may be responsible for mediating the effects of CGRP on LH pulses.
ISSN:	0022-3751 1469-7793