INDUCTION OF VASOACTIVE-INTESTINAL-PEPTIDE GENE-EXPRESSION AND PROLACTIN SECRETION BY INSULIN-LIKE GROWTH-FACTOR-I IN RAT PITUITARY-CELLS -EVIDENCE FOR AN AUTOPARACRINE REGULATORY SYSTEM

The effects of recombinant human insulin-like growth factor I (IGF-I) on both vasoactive intestinal peptide (VIP) and PRL production and gen e expression were studied using rat anterior pituitary cell, cultures grown in serum-free defined medium. We also examined whether pituitary VIP could be involved in the PRL response to IGF-I and hence in a par acrine regulatory system. Exposure of cultured anterior pituitary cell s to IGF-I (2.6 nM) for 3 h caused a significant decrease in both VIP content and media PRL. Treatment with IGF-I (from 0.65-5.2 nM) for 48 h increased VIP production and VIP messenger RNA (mRNA) accumulation, whereas only an increase in media and intracellular PRL content withou t changes in mRNA was observed. In all these experiments, IGF-I led to a decrease in both GH secretion and expression. Immunoglobulins G pur ified from VIP antiserum inhibited IGF-I-induced PRL release without a ffecting intracellular and mRNA levels. The inhibition of both GH secr etion and gene expression induced by IGF-I was not blocked by VIP anti serum. In conclusion, these results indicate that IGF-I induces VIP ge ne expression, and its secretion and also increases PRL secretion. The effect of IGF-I on PRL release is specifically mediated by VIP throug h a paracrine or autocrine mechanism.