Mechanisms of somatostatin action in pituitary cells

We have examined the mechanisms by which S-14 inhibits pituitary hormone secretion in a homogeneous cell population: the clonal GH4C1 cell line. The S-14 receptor in GH4C1 cells is coupled to Ni, a guanine nucleotide binding protein which mediates S-14-induced inhibition of VIP-stimulated adenylate cyclase activity, cyclic AMP production and hormone secretion. In addition, a functional Ni is required for S-14 to inhibit basal hormone secretion, an action which appears to be independent of cyclic AMP concentrations. Accumulating evidence indicates that the mechanism of S-14 action in somatotrophs is similar to that in GH4C1 cells. Although S-14 consistently inhibits basal GH secretion, its effects on basal cyclic AMP levels in normal pituitary cells are variable and often not significant (10-14). In contrast, S-14 inhibits prostaglandin and growth hormone releasing factor (GRF) stimulated cyclic AMP accumulation and GH release in parallel. Furthermore, S-14 partially blocks prostaglandin and GRF stimulation of adenylate cyclase activity in rat anterior pituitary membranes. Finally, pretreatment of primary cultures of rat pituitary cells with IAP antagonizes S-14 inhibition of both basal and GRF-stimulated GH release.