Acute and chronic galanin administration decreases hypothalamic galanin synthesis in both male and female adult rats: Evidence for a long-loop galanin autofeedback

Abstract

The secretion of growth hormone (GH) in both male and female rats is controlled by two main neuropeptides, GH-releasing hormone (GHRH), which is stimulatory, and somatostatin, which is inhibitory. Recently, it has been shown that galanin (GAL) also stimulates GH secretion, although the underlying mechanism is still unknown. It was the aim of this study to begin to elucidate if and how GAL regulates its own production at the hypothalamic and pituitary level. Rats underwent the following experimental trials. In experiment 1, adult male and female rats had blood samples collected at -15 minutes, -7.5 minutes, and immediately preceding a subcutaneous (s.c.) injection of GAL at a dose of either 50 or 200 microg/kg. Blood samples were collected at 5, 10, 15, 30, and 60 minutes, and the GH concentration was measured using a radioimmunoassay. The tissues were collected and analyzed for mRNA levels of hypothalamic and pituitary GAL. In experiment 2, adult male and female rats were treated long-term with 200 microg/kg GAL for 7 days s.c., and the pituitary and hypothalamus were analyzed for GAL mRNA. Serum GH concentrations were significantly increased in acutely dosed male and female rats regardless of the dosage level. For the male and female animals acutely dosed with both 50 and 200 microg/kg GAL, hypothalamic GAL mRNA was decreased, whereas pituitary GAL mRNA was affected by 200 microg/kg GAL only in females (increased). For the animals treated long-term with GAL, hypothalamic GAL mRNA was decreased while mRNA for pituitary GAL was increased. We conclude that regardless of the dosage and duration of treatment, administration of GAL negatively regulates hypothalamic GAL mRNA in a non-gender-specific way. Pituitary GAL synthesis appears to be stimulated particularly during chronic SCGAL administration.