Galaninergic Mechanisms Are Involved in the Regulation of Corticotropin and Thyrotropin Secretion in the Rat*

Abstract

Galanin (GAL), a 29-amino acid peptide, affects the secretion of several anterior pituitary hormones, including PRL and GH. Since GAL coexists with vasopressin and CRH in the hypothalamic paraventricular nucleus (PVN), we have studied the pharmacological and physiological actions of GAL on ACTH and TSH secretion in freely moving male rats. Cannulae were surgically implanted in the right atria and brain, intraventricular or adjacent to the PVN, of adult Sprague-Dawley rats. Seven days later, GAL (500 or 1000 ng) or saline was infused into the PVN, and serial blood samples were obtained 5, 10, 20, and 40 min after the infusion. Some animals were also stressed by the inhalation of ether vapors for 2 min after the PVN infusion. Basal ACTH concentrations were increased 2-fold in saline-treated rats; however, plasma ACTH levels were unchanged after GAL infusion. The exposure of rats to ether vapors for 2 min after the infusion of saline into the PVN increased plasma ACTH concentrations from 22.8 +/- 6.0 to 596.6 +/- 59.9 pg/ml 10 min later. However, the infusion of GAL into the PVN attenuated stress-induced ACTH secretion. After GAL infusion, peak ACTH levels (332.7 +/- 84.0 pg/ml) were attained 5 min after ether exposure, followed by a rapid decline at 10 min (P less than 0.001) and 20 min (P less than 0.05). Plasma TSH concentrations were unchanged by GAL or saline infusion and were not affected by ether vapor inhalation. To determine the physiological significance of GAL in the control of ACTH and TSH secretion, endogenous GAL was immunoneutralized by the infusion of 3 microliters GAL antiserum (GAL-AS) into the third cerebral ventricle 25 and 1 h before withdrawing blood samples every 15 min for 6 h. Animals treated with normal rabbit serum (NRS) served as controls. Plasma ACTH concentrations were unchanged by NRS during the 6-h period. However, infusion of GAL-AS raised plasma ACTH concentrations to over 400 pg/ml 75 min after infusion in some animals. In general, plasma ACTH concentrations were increased 4 h of the 6-h sampling period compared to levels in NRS-treated controls. In contrast, GAL-AS reduced TSH concentrations by 50% compared to control values. In contrast to these marked actions of centrally administered GAL, ACTH secretion from dispersed anterior pituitary cells in vitro was unaffected by GAL in concentrations up to 10(-6) M. Furthermore, GAL did not alter CRH (1 nM)-induced ACTH secretion.(ABSTRACT TRUNCATED AT 400 WORDS)