Insulin-like growth factor I disparately regulates prolactin and growth hormone synthesis and secretion: studies...

Although insulin-like growth factor I (IGF-I)'s inhibition of GH release is well documented, little is known of its control of GH synthesis at the posttranscriptional level. The manner by which IGF-I alters PRL synthesis and secretion is also unclear. This study was undertaken to examine the role IGF-I plays in regulating in vitro PRL and GH synthesis and release using the teleost pituitary model system. This model allows for isolation of nearly homogenous populations of distinct pituitary cell types that can be cultured in a completely defined, hormone-free medium. Tissues containing PRL cells and those consisting of GH cells were dissected from pituitaries of hybrid striped bass and exposed to varying concentrations of IGF-I, IGF-II, and insulin for 18-20 h. Exposure to graded doses of IGF-I markedly stimulated fractional, total, and newly synthesized PRL release in a dose-dependent fashion (ED50 for fractional release, 35 ng/ml or 4.6 nM; P < 0.0001). IGF-II and insulin also increased PRL release, but only at 10-fold higher concentrations than the lowest effective IGF-I dose. The total PRL content in the incubations and PRL synthesis, as measured by [35S]methionine incorporation, were not altered by IGF-I. By contrast, IGF-I potently reduced GH release (ED50, 29 ng/ml or 3.8 nM; P < 0.0001) and synthesis. Both 100 and 1000 ng/ml IGF-I decreased newly synthesized GH and total GH content (P < 0.001). Insulin and IGF-II mimicked IGF's action in attenuating GH release, but only at 10- to 11-fold higher concentrations. Taken together, these findings clearly indicate that IGF-I disparately regulates PRL and GH synthesis and secretion. We show that the effects of IGF-I on pituitary hormone release occur in a variety of species, suggesting that its actions are well conserved. The inhibition of GH release and synthesis by IGF-I probably reflects a negative feedback loop for maintaining tight control over GH cell function. These findings further indicate that IGF-I is a potent and specific secretagogue of PRL release in vertebrates.