Neurohypophyseal Neuregulin 1 Is Derived from the Hypothalamus as a Potential Prolactin Modulator

Although neuregulin 1 (Nrg1) has been identified in the rat hypothalamus, the localisation of Nrg1 in the hypothalamus-hypophyseal structure and its functions remain unclear and require further elucidation. In this study, we identified the existence of Nrg1β types I-III in the rat hypothalamus. We demonstrated that Nrg1 was partially localised in somatostatin-positive cells in the periventricular nucleus. It was also co-localised with arginine vasopressin in the supraoptic nucleus, median eminence and pituitary stalk. Nrg1 was also extensively distributed in the posterior pituitary (PP), including the projected neuronal fibres that surround the vascular structure and Herring bodies. Western blotting confirmed that these signals were primarily produced by soluble Nrg1 derived from a 45-kDa Nrg1 precursor mainly identified in the hypothalamus. Similar to Nrg1α, Nrg1β increased the prolactin (PRL) expression in rat pituitary RC-4B/C cells, which can be inhibited by an Akt inhibitor. In addition, Nrg1β had no apparent effect on growth hormone expression at the mRNA or protein levels. Collectively, we conclude that hypothalamic Nrg1 may be transported to the PP as the β form. We further hypothesise that Nrg1β may function via the regulation of PRL expression through a paracrine mechanism.