Growth hormone (GH) rebound rise following somatostatin infusion withdrawal: studies in dogs with the use of GH-releasing hormone and a GH-releasing peptide

Objective: Evidence has been presented that in both animals and humans the rebound secretion of growth hormone (GH) following withdrawal of an infusio n of somatostatin (SS) is due to the functional activation of the hypothala mic GH-releasing hormone (GH-RH) neurons of the recipient organism. Based o n this premise, this study has sought to assess the existence of functional interactions between endogenous GHRH released by a SS infusion withdrawal (SSIW) and growth hormone-releasing peptides (GHRPs), a class of compounds allegedly acting via GHRH. Methods: Five young dogs (3 to 4 years old, 2 male and 3 female) were admin istered, on different occasions, three consecutive intravenous boli of phys iological saline (0.1 ml/kg), or GHRH (2 mug/kg), or EP92632 (125 mug/kg), a GHRP compound, or GHRH plus EP92632 at the end of three cycles of 1-h SS infusions (8 mug/(kgxh)) or during a 6-h infusion of saline. Results: Under saline infusion (SALI), plasma GH levels were unaltered, whe reas each SSIW cycle was followed by similar GH secretory episodes. Adminis tration of the first GHRH bolus under SALI induced a rise in plasma GH conc entrations slightly higher than that induced by the first cycle of SSIW, bu t the GH response to the second and third GHRH boli was similar to that aft er SSIW. Following SSIW, the response to the first bolus of GHRH was higher than that during SALI, but the second and third cycles of SSIW induced GH responses similar to those evoked by the GHRH bolus. During SALI administra tion of the first bolus of EP92632 induced a rise in plasma GH which was hi gher than that induced by the first GHRH bolus, the second bolus elicited a GH peak of lesser amplitude and there was a partial restoration of the GH response to the third peptide bolus. SSIW strikingly enhanced the GH releas e to the first EP92632 bolus, a pattern also present, although to a lesser extent, with the second and third cycles of SSIW. Under SALI combined admin istration of GHR-H and EP92632 had a synergistic effect on GH release, but a progressive reduction was present in the GH response to the second and th ird GHRH plus EP92632 boli. SSIW increased only weakly the GH response to t he first co-administration of the peptides over that present after administ ration of EP92632 alone, and did not induce a GH response higher than that present during SALI when the second bolus of the peptides was administered; after the third SSIW a GH rise higher than that present during SALI was el icited by the combined administration of the peptides. Conclusions: (i) the uniformity of the GH rebound responses to multiple cyc les of SSIW may indicate that the latter activate a physiological mechanism which mimics that normally controlling GH pulse generation; (ii) EP92632 e licits, under our experimental conditions, a plasma GH rise higher than tha t induced by GHRH; (iii) SSIW enhances the GH response to EP92639 alone, to an extent reminiscent of that following combined administration of GHRH an d EP92632. This pattern reinforces the view that SSIW elicits release of en dogenous GHRH, and infers that the GHRP challenge after SSIW may be exploit ed in humans to distinguish between healthy and GH-deficient adults.