Plasma immunoreactive GHRH and serum GH concentrations following pulsatile GHRH 1-40 administration in GH deficient...

We have studied the clearance from plasma of immunoreactive growth hormone releasing hormone 1-40 (IR-GHRH) following intravenous (i.v.) and subcutaneous (s.c.) administration and the relationship between exogenous plasma IR-GHRH concentrations and GH secretion in five GH insufficient children receiving long term nocturnal pulsatile GHRH 1-40. The i.v. studies with GHRH 1-40 1 micrograms/kg demonstrated a distribution half life (t1/2) of 3.9 (SD 0.9) min and an elimination t1/2 of 53.1 (SD 3.2) min. In the s.c. studies the elimination phase was similar to the i.v. results but the transit time to the GHRH peak was slower than the i.v. distribution t1/2 9.9 (SD 3.6) min. These characteristics were maintained during successive pulses of subcutaneous GHRH. The mean IR-GHRH peaks following s.c. GHRH 1-40 administration of 1 microgram/kg and 2 micrograms/kg were 37- and 18-fold lower respectively than the mean IR-GHRH peak observed after the i.v. 1 microgram/kg bolus study. A significant correlation was shown between peak plasma IR-GHRH and serum GH concentrations during the s.c. (r = 0.75) but not the i.v. studies. Pulsatile GHRH administration has been shown to stimulate GH secretion and growth acceleration in GH insufficient children. Knowledge of the relationship between GHRH 1-40 absorption from the subcutaneous site and GH secretion is important for the development of an optimal GHRH treatment regimen in GH insufficient children.