This proposal will explore the feedback regulation of the growth hormone (GH) rhythm in a chronobiological context in the unanesthetized, chronically cannulated rat. The primary goal is to determine whether the rhythms of somatostatin (SS) and growth hormone-releasing factor (GRF) are generated by self- sustaining CNS neuronal oscillators or are passively driven. Phase-responses curves will be constructed to ascertain if (a) GH entrains the GH rhythm when circulating SS has been immunoneutralized and when SS perikarya in the periventricular and medial basal amygdaloid nuclei have been ablated, and (b)GRF entrains the GRF oscillator. The ability of periodic hGH injections to entrain the GRF oscillator of the female rat will also be assessed. To further characterize the nature of the SS rhythm, we will determine (a) the CNS loci from which GH-induced SS originates, (b) if SS if rhythmically released when endogenous GRF and GH are suppressed, and (c) if SS feedback inhibits its own release in vivo. Possible interactions between SS and GRF at the level of the CNS will be elucidated by determining if (a) GH stimulates SS release independently of the GRF perikarya in the arcuate nucleus and (b) if GRF stimulates SS release or suppresses GRF release in vivo. The pattern of GRF release will be inferred from the pattern of plasma GH in rats bearing lesions of the periventricular/medial basal amygdaloid nuclei and/or passively immunized with specific antiserums to SS-14 and SS-28. Somatostatin release will be detected by changes in GH responsiveness to exogenous hGRF in rata in which endogenous GRF has been immunoneutralized with a specific antiserum.
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