L. Stephen Frawley

Existence of Somatotrope Subpopulations which are Differentially Responsive to Insulin-Like Growth Factor I and Somatostatin*

It is generally accepted that hypothalamic somatostatin and hepatic insulin-like growth factor I (IGF-I)/somatomedin-C act directly on the pituitary to inhibit GH release, but it is not known whether all somatotropes are responsive to these agents. In the present study, we used a reverse hemolytic plaque assay to compare the acute (8 h) effects of somatostatin and IGF-I on the release of GH from individual cells in 24-h cultures of male rat pituitaries. Treatment with these factors caused comparable dose-dependent decreases in both the rate of plaque formation and the percentage of cells which released GH. In 8-h incubations, maximal (10(-8) M) doses of IGF-I or somatostatin alone decreased the percentage of GH-releasing cells to approximately the same degree (from 34.4% in controls to 29.7% and 28.4%, respectively), yet the effects of these factors were additive when both agents were applied to the same cells (to 24.5%). When we analyzed the sizes of plaques (an index of the amount of hormone released per cell) which resulted from these treatments, we noted that somatostatin was a much greater suppressor (to 11% of control value) of GH release than IGF-I (60% of controls). Coincubation with 10(-8) M GH-releasing factor had no effect on the percentage of GH-releasing cells at 8 h but completely overrode the inhibitory effect of IGF-I on plaque size without affecting the somatostatin-induced decrease in this regard. Taken together, these data suggest that IGF-I and somatostatin act, at least in part, on separate subpopulations of rat somatotropes. Somatostatin is a much more effective inhibitor of total GH release than IGF-I and appears to affect most, if not all, somatotropes. In contrast, IGF-I acutely inhibits GH release (prevents plaque formation) from some somatotropes, but does not seem to affect the remaining GH cells.

Effects of Prolactin on Target Cells

Prolactin is undoubtedly one of the most intensely studied of all hormones. Indeed, its putative biological functions are uniquely diverse, and its cell of origin has been exploited as a model system by legions of cellular and molecular biologists. Yet despite its popularity among investigators with divergent interests, surprisingly little is known about the manner in which the hormone exerts its effects on target cells. During the past few years, there have been several important advances in this area, including characterization of the prolactin receptor and identification of hepatic factors that may serve as extracellular mediators of the actions of this hormone. The purpose of this review is to evaluate these recent observations in light of previous findings and to provide an integrated update on the status of the field based on these considerations. Accordingly, the chapter will begin with the direct actions of prolactin and deal successively with target tissues and their responses, receptor characterization and activation, and putative components of the second messenger system. This will be followed by a discussion of the possibility that prolactin also exerts indirect effects on target cells through the mediation of liver factors.