Localization of prepro-growth hormone releasing factor mRNA in rat brain and regulation of its content by food deprivation and experimental diabetes

Growth hormone releasing factor (GRF) is the principal stimulatory hypothalamic neuropeptide controlling growth hormone (GH) secretion from pituitary somatotrophs. In this study we examined the hypothalamic and extrahypothalamic sites of preproGRF mRNA expression using both in situ hybridization and nuclease protection techniques. Each of these techniques confirmed that the principal site of GRF expression in CNS is within the hypothalamic arcuate nucleus with an additional population of neurons lying in the periventromedial region of the hypothalamus. PreproGRF mRNA was also detected at low levels in paraventricular and supraoptic nuclei, in piriform and neocortex, hippocampus, olfactory bulb, striatum, and brain stem, but not in anterior pituitary. However, the levels of preproGRF mRNA in these latter brain regions were approximately 20- to 50-fold lower than levels in whole hypothalamus. To extend previous observations, we then determined which brain loci modulate preproGRF mRNA levels in response to food deprivation or experimental diabetes mellitus. PreproGRF mRNA levels in both arcuate and periventromedial hypothalamic neurons declined 3- to 5-fold following food deprivation or streptozotocin-induced diabetes mellitus while the number of preproGRF expressing neurons was relatively unchanged in each experimental protocol; however, hybridization signal in piriform cortex and hippocampus was not affected by either experimental protocol. These data implicate two hypothalamic neuronal populations in modulating GH secretion and suggest specific modulation of hypothalamic preproGRF mRNA levels by food deprivation and diabetes.