Ultradian oscillations in somatostatin and growth hormone-releasing hormone mRNAs in the brains of adult male rats

Abstract

In the adult male rat, growth hormone (GH) secretion is characterized by an ultradian rhythm generated by the rhythmic interplay of the stimulatory effects of GH-releasing hormone (GHRH) and the inhibitory effects of somatostatin (Ss). Although considerable evidence indicates that GHRH and Ss are secreted in reciprocal 3- to 4-hr rhythms, the mechanism underlying the rhythmic secretion of these two neuropeptides is unknown. We tested the hypothesis that the rhythmic and reciprocal oscillations in secretion of Ss and GHRH are associated with parallel changes in synthesis and that this would be reflected by coincident oscillations in levels of the respective mRNAs. In the first experiment, Ss mRNA was significantly greater in the periventricular nucleus of animals sacrificed at the time of a presumed peak in the GH rhythm than in animals sacrificed at the time of a presumed trough; this variation was limited to the anterior third of this nucleus. Conversely, GHRH mRNA content throughout the arcuate nucleus was significantly greater at the time of a GH trough. In the second experiment, groups of animals were sacrificed during two consecutive cycles. In this set of animals, Ss mRNA content was 40% greater (P less than 0.005) during peak GH concentrations, whereas GHRH mRNA content was 42% greater (P less than 0.005) during the GH trough. This difference persisted when the two cycles were analyzed separately. The findings that the cellular mRNA content for Ss and GHRH varies in a reciprocal manner with the presumed secretion of these neuropeptides suggest that, like secretion, the synthesis of Ss and GHRH also varies rhythmically. The occurrence of this rhythm suggests a model for a transcriptional oscillator that may subserve the generation of this and possibly other neuroendocrine rhythms.