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

Abstract

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 microgram/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.

Usefulness of the desmopressin test in the postoperative evaluation of patients with Cushing's disease

“…Compared with our previous results (8), the data obtained in a larger group of normal individuals con®rm the consistent lack of signi®cant ACTH/cortisol responses to this peptide in this population (6,15,21) ± a feature that might be a consequence of an insuf®cient expression of V3 receptors in normal corticotrophs. This consideration prompted us to evaluate whether the desmopressin challenge might be of value in the postoperative follow-up of patients with Cushing's disease after successful surgery.…”

Recurrence of Cushing's Disease Preceded by the Reappearance of ACTH and Cortisol Responses to Desmopressin Test

“…It has been reported that desmopressin test is able to differentiate patients with Cushing's disease from the majority of normal subjects and patients with obesity, depression or pseudo-Cushing states [14,16,17,[22][23][24]. It has been reported that desmopressin test is able to differentiate patients with Cushing's disease from the majority of normal subjects and patients with obesity, depression or pseudo-Cushing states [14,16,17,[22][23][24].…”

ACTH and cortisol release following intravenous desmopressin: a dose–response study

“…The conclusion from previous studies of DDAVP‐induced ACTH release is that DDAVP is not a stimulant of the pituitary‐adrenal system in health (Malerbi et al ., 1996; Ceresini et al ., 1997). This has been used as a basic premize in subsequent studies (Newell‐Price et al ., 1997).…”

“…DDAVP induced ACTH and cortisol release has been shown in recent studies to reliably distinguish between Cushing's disease patients and subjects with depression (Malerbi et al ., 1996) and also to have potential application in the postoperative follow‐up of Cushing's patients (Colombo et al ., 1997). DDAVP can augment the pituitary‐adrenal response to CRH in healthy subjects (Ceresini et al ., 1997). It has proved to be a safe and well tolerated substance.…”