Administration of a nonpeptidyl growth hormone secretagogue, L-163,255, changes somatostatin pattern, but has no effect on patterns of growth hormone-releasing factor in the hypophyseal-portal circulation of the conscious pig

The activity of the growth hormone secretagog, L-163,255, on growth hormone (GH), growth hormone-releasing factor (GRF), and somatostatin (SRIF) level s was evaluated in a porcine model of hypophyseal portal blood (HPB) collec tion. Young, castrated pigs had HPB and jugular blood collected for approxi mate to 300 min, The blood collection was divided into discrete periods: ba seline (BL) approximate to 180 min; GH response period (RSP) approximate to 90 min; and positive control period following a GRF bolus, 30 min. RSP was divided into a dominant response period (DOM) and a tail (TL), The spontan eous relationship between HPB GRF and SRIF and peripheral GH during BL has been reported (Proc Soc Exp Biol Med 217:188-196, 1998), The apex of the GH pulse resulting from L-163,255 administration was nonrandomly associated ( P < 0.05) with descending periods of SRIF troughs. Frequency and amplitude of GRF and SRIF pulses, and frequency and depth of SRIF troughs were not di fferent between BL and the beginning of DOM (the 20-30 min of GH increase). GH AUC was significantly greater (P < 0.05) for DOM compared to BL and TL, and for TL compared to BL, GRF AUC tended to be greater (P < 0.1) for RSP compared to BL, but the majority of the increase was in the TL period. Ther e were no significant differences in the SRIF AUCs between the sampling per iods. Furthermore, in a separate experiment, fos activity (a marker of neur onal activation) in the hypothalamus of pigs was examined after either L-16 3,255 (1x or 4x), isotonic saline (control), or hypertonic saline (positive control) administration. There were no differences in fos activity in the GRF, SRIF, or CRH immunopositive neurons between L-163,255 treatment and co ntrol. The pituitaries of the L-163,255-treated pigs showed marked fos acti vation compared to the controls. In conclusion, L-163,255 in pigs has its p rimary effect at the level of the anterior pituitary,