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Effects of Ovine Corticotropin-Releasing Hormone Injection and Desmopressin Coadministration on Galanin and Adrenocorticotropin Plasma Levels in Normal Women

Chair of Geriatrics (G.C., M.F., G.V.), University of Parma, Parma; and the Department of Internal Medicine (P.P.), University of Torino, Torino, Italy; and Wyeth-Ayerst Research (I.M.), Radnor, Pennsylvania 19087

Address all correspondence and requests for reprints to: Dr. Graziano Ceresini, Chair of Geriatrics, University of Parma, Via don Bosco 2, 43100 Parma, Italy.

The neuropeptide galanin (GAL) has been shown to be located in the pituitary gland and to modulate the secretion of several pituitary hormones. In the human pituitary, GAL is almost exclusively located within corticotrophs. We examined whether GAL is secreted from corticotrophs in response to stimuli that induce ACTH release. Plasma levels of GAL and ACTH were evaluated in six healthy female subjects in the follicular phase of the menstrual cycle after the following treatments: 1) ovine CRH (oCRH) injection during saline (SAL) infusion, 2) oCRH injection during infusion of the arginine vasopressin analog desmopressin (DP), 3) SAL injection during DP infusion, and 4) SAL injection during SAL infusion. DP (4.3 ng/min·kg BW) or SAL was infused from 0–60 min. oCRH (1 µg/kg BW) or SAL was administered by a 2-min injection at 5 min.

The expected ACTH response to oCRH was enhanced by the concomitant DP administration (peak level, 10.39 ± 1.12 vs. 21.37 ± 3.43 pmol/L in SAL infusion plus oCRH injection vs. DP infusion plus oCRH injection, respectively; P < 0.05). The mean integrated ACTH response, expressed as the area under the curve, to SAL infusion plus oCRH injection vs. that to DP infusion plus oCRH injection was 288.23 ± 61.94 vs. 699.70 ± 91.80 pmol/L·60 min, respectively (P < 0.05). A slight, but not significant, increase was observed in ACTH values after DP infusion plus SAL injection compared to that after SAL infusion plus SAL injection challenge. Plasma GAL levels were highly variable. No changes in GAL levels were found concomitant to ACTH values in either experimental group. In fact, GAL levels were not significantly affected by either treatment. These data confirm that DP potentiates the ACTH response to CRH in humans. Furthermore, our results suggest that GAL is probably not cosecreted with ACTH in normal subjects. The possibility exists that GAL produced by corticotrophs exerts its action principally through a locally mediated paracrine or autocrine mechanism without being secreted into the bloodstream.

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