Endogenous Growth Hormone (GH) Secretion in Male Rats Is Synchronized to Pulsatile GH Infusions Given at 3-Hour Intervals*

Abstract

The feedback effects of GH on its own secretion were studied in conscious male rats receiving intermittent iv infusions of human GH. Male Sprague-Dawley rats (150-180 g) were implanted with double bore iv cannula. Infusions of human GH (hGH) or buffer were given for up to 32 h, while frequent microsamples (20 microliters) of blood were withdrawn simultaneously using an automatic blood-sampling system. The endogenous GH pulses became synchronized to pulsatile hGH infusions (2.1 U/kg.infusion) given at 3-h intervals. After two or more hGH infusions episodic GH release was present in most rats, and all endogenous pulses occurred concomitantly with the hGH infusions. After 24 h of hGH treatment the endogenous pulses were still synchronized to the every 3 h hGH infusions. In addition, the pulse amplitude was lower than that in vehicle-treated animals (74 +/- 12 vs. 215 +/- 35 ng/ml; P less than 0.01). At this time a complete (1.5-h) phase shift of the 3-hourly hGH infusions markedly suppressed endogenous GH pulses in all rats. In another experiment where the same daily dose of hGH was given in iv infusions every 1.5 h instead of every 3 h, the endogenous GH pulses were irregular, infrequent, and suppressed. Infusions at 3-h intervals of a lower dose of hGH (0.42 U/kg.infusion) did not affect the timing or amplitude of endogenous GH pulses compared to those in buffer-infused animals. The endogenous GH pulses were not synchronized between animals given 0.42 U/kg hGH or buffer at 3-h intervals. It is concluded that the endogenous GH pulses in male rats became synchronized to intermittent infusions of hGH at 3-h (but not 1.5-h) intervals. The fact that there were no endogenous pulses between the 3-hourly infusions suggests that the feedback effect of a GH pulse lasts for approximately 3 h. This mechanism may be involved in the control of the GH secretory pattern in male rats.