Activation of Hypothalamic Gamma‐Aminobutyric Acid Receptors Resets the Pendulum of the Growth Hormone Clock

Abstract

Abstract Plasma levels of growth hormone in male rats exhibit an ultradian rhythm having a periodicity of 3 to 4 h, bursts of growth hormone being separated by troughs when growth hormone secretion ceases. To determine if neurons in the vicinity of somatostatin neurons in the preoptic/anterior hypothalamic area participate in the generation of the rhythm, we temporarily inhibited this region with injections of the gamma-aminobutyric acid agonist, muscimol, in unanaesthetized rats previously prepared with a venous catheter and stereotaxically implanted intracerebral guide tubes. The injection resulted in an immediate burst of growth hormone release, followed by a trough period and another growth hormone burst, 3.4 +/- 0.1 h later. The induction of a trough and synchronization of growth hormone bursts was not reproduced by a burst of intravenously injected exogenous growth hormone at least as large as the first burst initiated by muscimol. These findings indicate that, in the short term, the ultradian rhythm is independent of growth hormone feedback and provide the first evidence that structures in the anterior hypothalamus receiving a gamma-aminobutyric acid input are an important component of the neural generator of the ultradian rhythm of growth hormone.