Short-term met-hGH infusion inhibits somatotroph response to growth hormone releasing hormone (1–44)

Abstract

To determine whether the short-term administration of growth hormone inhibits pituitary responsiveness to h-GHRH we measured the somatotroph response to h-GHRH-44 (0.3 μg/kg) stimulation in ten normal subjects from the third to the fifth hour of an infusion of met-hGH (2 μg/kg/h) or saline. Insulin, insulin-like growth factors (IGF), somatomedins, free fatty acids (FFA), glycerol, and glucose levels also were assessed during the first 3 hours of infusion. Steady-state GH levels of 5 to 20 ng/mL were achieved during met-hGH infusion. No significant changes in IGF, insulin, or glucose levels measured at the beginning and again after three hours of infusion occurred within or between conditions. Infusion of met-hGH was associated with a significantly greater increase in FFA levels (69 ± 50 μmol/L following saline v 433 ± 57 μmol/L following three hours of met-hGH infusion ( P < .001)). The somatotroph response to h-GHRH-44 was significantly blunted during met-hGH infusion (incremental area under the GH/time curve decreasing from 1,196 ± 183 (ng/mL) × min to 380 ± 139 (ng/mL) × min ( P < .005)). These data demonstrate that this blunting can occur following short-term exogenous GH administration and at serum GH levels comparable to those achieved during naturally occurring bursts of GH secretion. They also suggest that acute mediation of GH release must occur, at least in part, at the pituitary somatotroph level and that IGFs and/or insulin may not be the primary inhibitors. This phenomenon may be directly or indirectly due to GH-dependent metabolic factors such as FFA or glycerol. The lipolytic effect of GH in conjunction with the inhibitory effect of lipolytic products on GH secretion may represent an important feedback loop in the physiologic control of GH release.