Autoregulation of the rat prolactin gene in lactotrophs

The autoregulation of prolactin (PRL) secretion in the rat has been demonst rated at both the hypothalamus and the pituitary levels.: Studies on the di rect negative feedback effect of PRL in the lactotrophs have concentrated o n the acute effect on PRL secretion which does not involve change in PRL sy nthesis. In this study, we have developed a cotransfection assay in somatol actotrophs where we examine the effect of PRL on the transcription of its o wn gene. We found that oPRL, at physiological concentrations, exerts a stro ng and specific inhibition of the rPRL gene transcription in PRL-deficient GC cells. This effect:is mediated by both the intermediate and the long for ms of PRL receptor. The inhibition was also reproduced in GH(3) cells, whic h secretes PRL, by adding exogenous oPRL in the presence of anti-rat PRL an tiserum to neutralize endogenous rPRL. Cellular specificity was demonstrate d by testing this regulation in: non-pituitary cell types where no modulati on of the PRL promoter reporter gene could be elicited by PRL, even with Co transfection with the Pit-1 expression vector. Finally, deletions of the, r PRL promoter indicate that the full inhibitory effect of PRL requires the s ame regulatory domains (proximal and distal) that have been described for t he other PRL gene regulators. These results strongly suggest the existence of the extra-short loop regulation of the rat PRL at the transcriptional le vel. (C) 1999 Published by Elsevier Science Ireland Ltd. All rights reserve d.