LACK OF VASOACTIVE INTESTINAL PEPTIDE-RELEASING PROPERTY IN PROLACTINCELLS FROM OVARIECTOMIZED RATS - CONTRIBUTION OF POST-TRANSDUCTIONAL IMPAIRMENTS

We have demonstrated recently that in menopausal women and in ovariect omized rats the deficiency of circulating oestrogens impairs vasoactiv e intestinal peptide (VIP) efficacy in stimulating prolactin (PRL) rel ease. The present study was designed to investigate whether the lack o f VIP-induced PRL, release after ovariectomy is a consequence of a def ect at the receptor-transductional or post-transductional level. For t his purpose we evaluated the VIP receptor function, by measuring VIP-s timulated cyclic adenosine monophosphate (AMP) formation, and the effi cacy of the cyclic AMP-dependent PRL release in pituitary cells from c ontrol and ovariectomized animals. We observed that VIP induced a sign ificantly higher stimulation of adenylate cyclase in pituitary homogen ates from ovariectomized rats than in those from control animals. This effect appeared to be linked to an increased efficiency of the G, cou pling protein, because superimposable results were obtained by using t he non-hydrolysable guanosine triphosphate (GTP) analogue, 5-guanylyli midodiphosphate. On the contrary, the cyclic AMP analogue, 8-Br-cAMP, that potently stimulated PRL release from control pituitary cells was completely ineffective in cells from ovariectomized rats. The present data indicate that in PRL-secreting cells from ovariectomized rats a d efect in the post-transductional mechanism that couples the VIP recept or to PRL secretion, rather than a reduction of receptor function, pos sibly accounts for the lack of VIP efficacy.