ALPHA-MSH POTENTIATES THE RESPONSIVENESS OF MAMMOTROPES BY INCREASINGCA2+ ENTRY

It is well known that the suckling stimulus renders mammotropes consid erably more responsive to prolactin (PRL)-releasing stimuli, and the n eurointermediate lobe peptide cr-melanocyte-stimulating hormone (alpha -MSH) has been proposed to play a pivotal role in this priming. The ob jectives of the present study were to determine whether alpha-MSH coul d act directly on pituitary cells to potentiate PRL release in respons e to two physiologically relevant PRL secretagogues, thyrotropin-relea sing hormone (TRH) and ATP, and, if so, to identify the mechanism by w hich this priming phenomenon is manifested. To this end, we cultured a nterior pituitary cells from lactating rats overnight and then subject ed them to a reverse hemolytic plaque assay for PRL to evaluate their responses to various test agents. We found that alpha-MSH, which had n o effect on PRL export when tested alone, augmented by more than three fold the secretory responses to TRH and ATP. Next, we utilized digital -imaging fluorescence microscopy of fura 2 to evaluate the role of int racellular Ca2+ in this process. We found that PRL export induced by p harmacological activation of L-type voltage-operated calcium channels was also potentiated by alpha-MSH, as was Ca2+ entry induced by TRH. O ur results indicate that alpha-MSH acts as a mammotrope-priming agent on a subset of mammotropes by increasing Ca2+ entry induced by PRL sec retagogues.