Decreased galanin mRNA levels in growth hormone-releasing hormone neurons after perinatally induced growth retardation

Intrauterine growth retardation (IUGR) is associated with persistent postna tal growth retardation accompanied by dysfunction of the hypothalamic compo nents of the growth hormone (GH) axis. At the adult stage, th-is is reflect ed by increased somatostatin (SS) and decreased neuropeptide Y (NPY) mRNA l evels, whereas the GH-releasing hormone (GHRH) mRNA levels are normal and t he output of GH remains unchanged. To extend our insight into the hypothala mic control of GH secretion in growth retarded rats, we determined galanin (GAL) mRNA levels at the adult stage of perinatally malnourished (i.e. IUGR and early postnatally food restricted) rats. Analyses included comparison of GAL mRNA levels in GHRH neurons in perinatally malnourished adult rats u sing a sen-ii-quantitative double labeling in situ hybridization technique. We report that IUGR is accompanied by a 60% decrease in GAL mRNA levels in all GHRH neurons in the male IUGR group whereas a tendency towards a decre ase was observed in the male early postnatally food restricted (FR) group. These effects became more pronounced when the analysis was restricted to GH PH neurons coexpressing GAL mRNA i.e. decreased GAL mRNA levels were seen i n both male and female IUGR rats and in FR males. These data show that GAL mRNA levels in GHRH neurons are persistently decre ased after perinatal malnutrition. Taking these results together with our p revious data on SS, NPY and GHRH mRNA levels, we can conclude that IUGR lea ds to a reprogramming of the hypothalamic regulation of GH secretion.