Effects of low dose ovine corticotropin-releasing hormone in humans: endocrine relationships and beta-endorphin/beta-lipotropin responses.

The effects of low doses (0.03 and 0.1 microgram/kg) of ovine CRH (oCRH) on plasma beta-endorphin/beta-lipotropin (beta End/beta LPH), ACTH, and corticosteroid levels were studied in normal men. The 0.03 microgram/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 beta End/beta LPH 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 beta End-immunoreactive materials in basal and post-oCRH (0.1 microgram/kg) plasma samples revealed an average basal beta End to beta LPH 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 beta End from the anterior pituitary.