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Sex-related naloxone influence on growth hormone-releasing hormone-induced growth hormone secretion in normal subjects
Authors:A Barbarino  L De Marinis  A Mancini  C D'Amico  M Passeri  P Zuppi  P Sambo  A Tofani
Affiliation:1. Department of Global Regulatory Affairs – CMC, Amgen, Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, USA;2. University of Southern California, School of Pharmacy, 1985 Zonal Ave, Los Angeles, CA 90089, USA;3. Cognition Corporation, 24 Hartwell Ave, Lexington, MA 02421, USA;4. Biotherapeutic Development & Supply, Janssen Pharmaceuticals, 1000 Route 202 South, Raritan, NJ 08807, USA;5. Department of Global Regulatory Affairs – CMC; Amgen Ltd, 1 Uxbridge Business Park, Sanderson Road, Uxbridge UB8 1DH, United Kingdom;6. Product Quality Management, Janssen Pharmaceuticals, 1000 Route 202 South, Raritan, NJ 08807, USA;7. Biotherapeutic Development & Supply, Janssen Pharmaceuticals, Barnahely, Ringaskiddy, Co.Cork, Ireland;8. Department of Global Regulatory Affairs – CMC, Amgen Inc., 40 Technology Way West Greenwich, RI 02817, USA;9. Biotherapeutic Development & Supply, Janssen Pharmaceuticals, 200 Great Valley Pkwy, Malvern, PA 10355, USA
Abstract:The effect of opiate-receptor antagonist naloxone on growth hormone (GH) release after growth hormone-releasing hormone (GHRH) 1-44 administration was investigated in ten normal men and 18 normal women during different phases of their menstrual cycle. Naloxone was infused at a rate of 1.6 mg/h in women and 1.6- and 3.2 mg/h in men, starting one hour before GHRH administration (50 micrograms iv as a bolus). On different day sessions, naloxone, GHRH, or saline were administered as controls. Naloxone infusion reduced the GHRH-induced GH release in normal women. The mean % inhibition of peak GH response was 83% during follicular phase, 46.5% during periovulatory phase, and 77.6% during luteal phase. On the contrary, in normal men, both doses of naloxone infusion were ineffective in blunting the GH response to GHRH. Our studies indicate that naloxone infusion was capable of inhibiting GH release induced by direct stimulation with GHRH in normal women, suggesting an opiate-antagonist action at the anterior pituitary level. The absence of such an effect in normal men strongly indicates a sex dependence of naloxone effects and suggests a role of the sexual steroid environment in opioid modulation of pituitary hormone secretion.
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