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Journal of Clinical Endocrinology & Metabolism Vol. 66, No. 1 10-15
doi:10.1210/jcem-66-1-10
Copyright © 1988 by the Endocrine Society.
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Effects of Low Dose Ovine Corticotropin-Releasing Hormone in Humans: Endocrine Relationships and β: Endorphin/β-Lipotropin Responses*

STANLEY J. WATSON, JUAN F. LOPEZ, ELIZABETH A. YOUNG, JR., WYLIE VALE, JEAN RIVIER and HUDA AKIL

Mental Health Research Institute, University of Michigan Ann Arbor, Michigan 48109-0720
The Clayton Foundation, Laboratories for Peptide Biology, The Salk Institute La Jolla, California 92037

Address requests for reprints to: Dr. Stanley J. Watson, Mental Health Research Institute, University of Michigan, 205 Washtenaw Place, Ann Arbor, Michigan 48109.

The effects of low doses (0.03 and 0.1 µg/kg) of ovine CRH (oCRH) on plasma β-endorphinβ-lipotropin (βEnd/ βLPH), ACTH, and corticosteroid levels were studied in normal men. The 0.03 µg/kg oCRH dose produced a reproducible response, with a rapid increase in plasma oCRH to peak levels between 45 and 95 fmol/mL and an appropriate doubling of plasma peptide and corticosteroid concentrations. The relationship between the corticosteroid rise and the rapid βEnd/βLPH and ACTH declines suggested negative feedback by corticosteroids on the release of these pituitary products. Plasma oCRH levels were proportionate to those reported in studies using much higher oCRH doses, and produced plasma oCRH levels in the reported range for the hypophyseal portal circulation. Molecular sieving of the βEnd-immunoreactive materials in basal and postoCRH (0.1 µg/kg) plasma samples revealed an average basal /3End to /3LPH ratio of 1:1.5; 15 min after oCRH stimulation the average ratio was 4:1. We conclude that a low (threshold) dose of oCRH can reliably stimulate POMC peptide secretion and may preferentially release βEnd from the anterior pituitary

* This work was supported in part by NIMH Grant MH-36168 (to S.J.W. and H.A.) NIMH Research Scientist Development Award MH-00427 (to E.Y.), NIMH Training Grant MH-15794 (to J.L.), and NIH Grant AM-26741 (to J.R.).

Received February 2, 1987.




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