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The Short-Term Infusion of Ovine Corticotropin-Releasing Hormone Does Not Alter Luteinizing Hormone Concentrations in Young Adult Men¹

Division of Endocrinology and Metabolism, Department of Pediatrics, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908

Address all correspondence and requests for reprints to: Daniel L. Metzger, M.D., Endocrinology and Diabetes Unit, British Columbia’s Children’s Hospital, 4480 Oak Street, Room 1A46, Vancouver, British Columbia, Canada V6H 3V4. E-mail: dmetzger{at}wpog.childhosp.bc.ca

Chronic stress leads to suppression of the hypothalamic-pituitary-gonadal (HPG) axis with decreased plasma LH concentrations. This is believed to be due to the influence of elevated levels of endogenous CRH mediated via the endogenous opiate peptide receptor. Efforts to reproduce this phenomenon with exogenous CRH have produced varied results depending on the dose and route of administration of CRH as well as on the species, gonadal state, and endogenous opiate peptide system tone of the experimental subjects. In humans, conflicting results for CRH-induced suppression of the HPG axis exist for women, and the issue has not been addressed sufficiently in men. We, therefore, studied the effects of a 4-h infusion of ovine CRH (oCRH) on LH secretion in 11 healthy, nonobese young adult men (age range, 20–33 yr). Subjects were admitted to the General Clinical Research Center on 4 occasions in randomized order. They underwent blood sampling for LH at 10-min intervals from 1800–0600 h. From 2200–0200 h, subjects received one of the following iv infusion protocols in blinded fashion: a normal saline (NS) bolus and NS infusion, a naloxone (NAL) bolus (4 mg) and NAL infusion (2 mg/h), a NS bolus and oCRH infusion (1 µg/kg·h; maximum, 75 µg/h), and a NAL bolus and both NAL and oCRH infusions, using the above-mentioned doses. For each time point, serum LH values from the four experimental conditions were compared by one-way ANOVA with repeated measures; the paired t test was applied post-hoc. This experimental model is predicted to have a ß-error of less than 0.10 for identifying a 1.0 U/L change in LH levels. As expected, NAL was associated with a transient, but significant, rise in serum LH concentrations compared to those in the NS control. On the other hand, oCRH administration did not result in any significant alteration in either basal or NAL-stimulated LH levels. We conclude that exogenous oCRH administration does not significantly alter pituitary secretion of LH in healthy men. We speculate that any suppressive effect of CRH on the HPG axis occurs at the level of the hypothalamus.

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