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) levels was evaluated in a porcine model of hypophyseal portal blood (HPB) collection. Young, castrated pigs had HPB and jugular blood collected for approximately 300 min. The blood collection was divided into discrete periods: baseline (BL) approximately 180 min; GH response period (RSP) approximately 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 spontaneous 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 different 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. There were no significant differences in the SRIF AUCs between the sampling periods. Furthermore, in a separate experiment, fos activity (a marker of neuronal activation) in the hypothalamus of pigs was examined after either L-163,255 (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 control. The pituitaries of the L-163,255-treated pigs showed marked fos activation compared to the controls. In conclusion, L-163,255 in pigs has its primary effect at the level of the anterior pituitary.
Drisko
J E
JE
Department of Basic Animal Science Research, Merck Research Laboratories, Rahway, New Jersey 07065, USA. jennifer_drisko@merck.com
Faidley
T D
TD
Zhang
D
D
McDonald
T J
TJ
Nicolich
S
S
Hora
D F
DF
Cunningham
P
P
Li
C
C
Rickes
E
E
McNamara
L
L
Chang
C
C
Smith
R G
RG
Hickey
G J
GJ
D000818:Animals; D013006:Growth Hormone / Q000378:metabolism; D013007:Growth Hormone-Releasing Hormone / Q000378:metabolism*; D007150:Immunohistochemistry; D010880:Piperidines / Q000494:pharmacology*; D010902:Pituitary Gland / Q000378:metabolism*; D011168:Portal System / Q000378:metabolism*; D013004:Somatostatin / Q000378:metabolism*; D013141:Spiro Compounds / Q000494:pharmacology*; D013552:Swine
D010880:Piperidines; D013141:Spiro Compounds; C102119:L 163255; D013004:Somatostatin; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone