Intracerebroventricular and intravenous administration of growth hormone secretagogue L-692,585, somatostatin, neuropeptide Y and galanin in pig: dose-dependent effects on growth hormone secretion.

Central regulation of growth hormone (GH) secretion by the GH secretagogue, L-692,585 (585), was determined in Yorkshire barrows (40-45kg BW) with intracerebroventricular (icv) stainless steel cannulas placed by stereotaxic coordinates and indwelling external jugular vein (iv) cannulas for injecting 585 or saline during 3h serial blood sampling. Dose-dependent effects of 585 were determined by icv injections of saline vehicle, 3, 10, and 30microg/kg BW by once daily increment. A switchback study of iv and icv 585 treatment determined central and peripheral regulation of GH secretion by the secretagogue at 30microg/kg BW. When administered icv, 585 increased GH concentration in a dose-dependent manner, with a return to baseline by 60min. GH secretion was attenuated by increased numbers of icv 585 injections (p<0.05); however, it was not affected by increased numbers of iv 585 injections. Icv administration of somatostatin (SRIF) decreased (p<0.05) GH secretion compared with saline-treated controls, and decreased (p<0.05) peak GH response when given in combination with 585 as compared with 585 alone. Porcine galanin (pGAL) modestly increased (p<0.05) GH levels compared with saline controls, but when given icv in combination with 585 peak GH response was lower (p<0.05) compared with 585 alone. Porcine neuropeptide Y (pNPY) administered icv was without effect on GH levels compared with saline controls and decreased (p<0.05) peak GH response when given in combination with 585 as compared with 585 alone. The pharmacological actions by icv administration indicate that the GH secretagogue and neuropeptides act at the level of both porcine pituitary and hypothalamus.