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This Article Full Text Full Text (PDF) All Versions of this Article: 566/3/921    most recent jphysiol.2005.085662v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Bowe, J. E Articles by O'Byrne, K. T Search for Related Content PubMed PubMed Citation Articles by Bowe, J. E Articles by O'Byrne, K. T

¹ Division of Reproductive Health, Endocrinology and Development
² Cardiovascular Division
³ Department of Pharmacology and Therapeutics, New Hunt's House, King's College London, Guy's Campus, London SE1 1UL, UK
⁴ Henry Wellcome Laboratory for Integrative Neuroscience and Endocrinology, Dorothy Hodgkin Building, University of Bristol, Bristol BS1 3NY, UK

Calcitonin gene-related peptide (CGRP) is involved in a variety of stress responses in the rat. Central administration of CGRP activates the hypothalamo–pituitary–adrenal 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 µg) completely blocked the suppression of LH pulses induced by 1.5 µg I.C.V. CGRP and significantly attenuated the suppression of pulsatile LH secretion induced by 5 µg 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 µg I.C.V. CGRP. Co-administration (I.C.V.) of CGRP (1.5 µg) with the µ and opioid receptor-specific antagonists naloxone (10 µg) and norbinaltorphimine (5 µg), respectively, blocked the CGRP-induced suppression of LH pulses, whilst I.C.V. co-administration of CGRP (1.5 µg) with the opioid receptor-specific antagonist naltrindole (5 µg) 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 µ and , but not the , opioid receptors may be responsible for mediating the effects of CGRP on LH pulses.

(Received 25 February 2005; accepted after revision 12 May 2005; first published online 19 May 2005)
Corresponding author J. E. Bowe: 2.36 New Hunt's House, Guy's Campus, London SE1 1UL, UK. Email: james.bowe{at}kcl.ac.uk