Endogenous hypothalamic somatostatins differentially regulate growth hormone secretion from goldfish pituitary somatotropes in vitro

Using Southern blot analysis of RT-PCR products, mRNA for three different somatostatin (SS) precursors (PSS-I, -II, and -III), which encode for SS(14), goldfish brain (gb)SS(28), and [Pro(2)]SS(14), respectively, were detected in goldfish hypothalamus. PSS-I and -II mRNA, but not PSS-III mRNA, were also detected in cultured pituitary cells. We subsequently examined the effects of the mature peptides, SS(14), gbSS(28), and [Pro(2)]SS(14), on somatotrope signaling and GH secretion. The gbSS(28) was more potent than either SS(14) or [Pro(2)]SS(14) in reducing basal GH release but was the least effective in reducing basal cellular cAMP. The ability of SS(14), [Pro(2)]SS(14), and gbSS(28) to attenuate GH responses to GnRH were comparable. However, gbSS(28) was less effective than SS(14) and [Pro(2)]SS(14) in diminishing dopamine- and pituitary adenylate cyclase-activating polypeptide-stimulated GH release, as well as GH release resulting from the activation of their underlying signaling cascades. In contrast, the actions of a different 28-amino-acid SS, mammalian SS(28), were more similar to those of SS(14) and [Pro(2)]SS(14). We conclude that, in goldfish, SSs differentially couple to the intracellular cascades regulating GH secretion from pituitary somatotropes. This raises the possibility that such differences may allow for the selective regulation of various aspects of somatotrope function by different SS peptides.