We have studied the regulation of somatostatin (SS) and growth hormone-releasing hormone (GHRH) gene expression in the brain of the laboratory rat. We report that hypophysectomy in the adult male reduces SS mRNA in cells of the periventricular nucleus (PeN), while GH reverses this effect. We demonstrate that cellular levels of SS mRNA in the PeN are higher in male compared to female animals. We report that castration reduces cellular levels of GHRH mRNA and SS mRNA in the arcuate nucleus and PeN, respectively, and that testosterone reverses this effect through an androgen receptor-dependent mechanism. Finally, we present a theoretical model to explain the generation of the ultradian rhythm in GH secretion, which implicates the reciprocal interaction between GH feedback and the transcriptional regulation of the SS and GHRH genes and the kinetics of these relationships.