In vivo evidence of a positive role for somatostatin to optimize pulsatile growth hormone secretion
Turner, J.P.; Tannenbaum, G.S.
American Journal of Physiology 269(4 Pt 1): E683-E690
1995
ISSN/ISBN: 0002-9513 PMID: 7485482 Document Number: 452566
Despite convincing evidence that somatostatin (SRIF) and growth hormone (GH)-releasing factor (GRF) individually play crucial roles in GH regulation, the nature of the interplay between these two hypothalamic hormones is far from clear. In the present study, we used the long-acting SRIF analogue, octreotide, as a probe in both the normal and mutant dwarf (dw) rat 1) to further elucidate the temporal nature of the SRIF-GRF interaction in vivo and 2) to define possible mechanisms of action of SRIF in generating pulsatile GH secretion. Normal free-moving adult male rats pretreated with octreotide (25 and 50 mu-g iv) and subsequently challenged with GRF (1 mu-g iv) exhibited a markedly blunted GH response to exogenous GRF 1 h after treatment. In contrast, preexposure to octreotide for 3 h produced a two- to threefold augmentation in GH responsiveness to GRF. Compared with normal saline-pretreated controls, 3-h pretreatment with octreotide produced a 14- to 16-fold augmentation in the postinhibitory rebound release of GH after the coadministration of native SRIF-14 and GRF (P lt 0.001). In dw rats, which show a selective reduction in GH synthesis and storage, 3-h preexposure to octreotide failed to significantly alter GRF-induced GH release. These results demonstrate that, in the normal male rat, a 3-h period of exposure to the SRIF analogue octreotide is sufficient to enhance GH responsiveness to GRF. Our findings suggest that this effect is due to a SRIF-mediated buildup of pituitary GH stores in a readily releasable pool. We conclude that SRIF is not only inhibitory to GH but has an important positive role to play in the generation of GH pulses by preparing the somatotroph to respond optimally to the next pulse of hypothalamic GRF.