Direct effects of corticotrophin-releasing hormone on stimulated growth hormone secretion

OBJECTIVE This study evaluated the effect of corticotrophin-releasing hormone (CRH) on growth hormone releasing hormone (GHRH)-stimulated growth hormone (GH) release in man. DESIGN Six healthy adult volunteers (age 20-35 years) were studied. On different occasions they each received an intravenous bolus of saline, CRH(1-41) (100 mu g), adrenocorticotrophic hormone (ACTH) [Synacthen (500ng/m(2))] or hydrocortisone (50mg), followed 30 minutes rater by an intravenous bolus of either GHRH-(1-29)-NH2 (1.0 mu g/kg) or saline. MEASUREMENT Serum GH concentrations were measured using an immunoradiometric assay, and cortisol concentrations were measured by commercial radioimmunoassay. TSH concentrations were measured using a solid phase immunoradiometric assay kit. RESULTS Pretreatment with CRH(1-41) attenuated the GH response to GHRH [saline/GHRH-(1-29)-NH2 20.2 +/- 6.2 mU/l; CRH(1-41)/GHRH-(1-29)-NH2 10.9 +/- 2.8 mU/l (P = 0.01)]. This effect was not due to the rise in ACTH or cortisol induced by CRH(1-41), since pretreatment with either ACTH or hydrocortisone significantly augmented the GH response to GHRH-(1-29)-NH2 in the same subjects [ACTH/GHRH-(1-29)-NH2 30.3 +/- 8.8 mU/l (P = 0.01); hydrocortisone/GHRH-(1-29)-NH2 36.4 +/- 11.2 mU/l (p = 0.02)]. CONCLUSION Our data suggest that the inhibitory effect of CRH(1-41) on GHRH-(1-29)-NH2-induced GH release is not a result of ACTH or cortisol release but reflects a direct action of CRH on GH secretion, possibly via stimulation of somatostatin release. The acute rise in GH following glucocorticoid administration could be explained in part by a rapid suppression of endogenous CRH.