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

Abstract

The effects of recombinant human insulin-like growth factor I (IGF-I) on both vasoactive intestinal peptide (VIP) and PRL production and gene 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 paracrine regulatory system. Exposure of cultured anterior pituitary cells 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 without changes in mRNA was observed. In all these experiments, IGF-I led to a decrease in both GH secretion and expression. Immunoglobulins G purified from VIP antiserum inhibited IGF-I-induced PRL release without affecting intracellular and mRNA levels. The inhibition of both GH secretion and gene expression induced by IGF-I was not blocked by VIP antiserum. In conclusion, these results indicate that IGF-I induces VIP gene expression, and its secretion and also increases PRL secretion. The effect of IGF-I on PRL release is specifically mediated by VIP through a paracrine or autocrine mechanism.

Direct Action of Serotonin on Prolactin, Growth Hormone, Corticotropin and Luteinizing Hormone Release in Cocultures of Anterior and Posterior Pituitary Lobes: Autocrine and/or Paracrine Action of Vasoactive Intestinal Peptide

“…It is well established that VIP stimulates PRL release and, in previous works, we have demonstrated that pituitary VIP mediates the effect of IGF-I, TRH and dopamine withdrawal on PRL release, through an autocrine or paracrine action [30, 31, 32]. In the present study, 5-HT induced a fast VIP release, with a profile similar to only that of PRL.…”

“…As we could not find any measurable amount of these hormones in the PP cultures, we believe that a new peptidergic PRL-releasing factor postulated to be synthesized by non-POMC secreting IL cells [28, 29]could explain the increase of basal PRL and VIP release in the cocultures. In fact, we have previously demonstrated that several PRL modulators, such as IGF-I, TRH, T 3 or dopamine induce similar responses of PRL and pituitary VIP in vitro [30, 31, 32]. On the contrary, the presence of PP cells inhibited GH release in the cocultures.…”

“…Furthermore, as we have previously demonstrated that vasoactive intestinal peptide (VIP) mediates the PRL release induced by insulin-like growth factor I (IGF-I) thyrotropin-releasing hormone and dopamine withdrawal through an autocrine or paracrine action [30, 31, 32], an additional aim of this work was to study whether 5-HT affects pituitary VIP release and, consequently, the possible implication of this neuropeptide as mediator of 5-HT action in vitro.…”

Implication of Pituitary Vasoactive Intestinal Peptide in Dopaminergic Inhibition of Estrogen-Induced Pituitary Hyperplasia and Vascular Endothelial Growth Factor Expression

“…Heparinized blood samples were centrifuged and plasma stored at –20°C for subsequent PRL determination. The VIP contents in pituitary, hypothalamus, and cortex samples were determined as previously described [13], using an antiserum against porcine VIP (generously provided by Dr. L. Cacicedo). Pituitary as well as serum PRL levels were measured by radioimmunoassay using materials generously provided by the National Pituitary Hormone Distribution Program (National Institute of Arthritis, Metabolism, and Digestive Diseases, Bethesda, Md., USA).…”

“…However, it is still not well understood how these mechanisms are coordinated to induce lactotrope hyperplasia and tumorigenesis. On the other hand, both we and others have reported the role of pituitary vasoactive intestinal peptide (VIP) as an autocrine/paracrine modulator of both basal and stimulated prolactin (PRL) release in vitro [11, 12, 13, 14, 15, 16], and, in a previous study [17], we have demonstrated that pituitary VIP mediates, at least partially, the lactotrope hyperplasia as determined on the basis of pituitary weight and pituitary proliferating cell nuclear antigen (PCNA) content and hyperprolactinemia induced by E through an autocrine/paracrine action. This study also showed that TGF-β1, an autocrine/paracrine factor which inhibits the lactotrope response to E, is simultaneously downregulated by pituitary VIP, displaying a multistep sequence of mediation in the E-induced lactotrope proliferation at the pituitary level.…”