Progestin receptors in prolactin and growth hormone producing tumours in rats.

Abstract

Progesterone and corticosterone have a similar effect on the production of growth hormone (GH) and prolactin (Prl) by pituitary tumour cells (GH3 cells) in culture. Previously we have shown that progesterone has a high affinity for the glucocorticoid receptors in these cells. Progesterone may therefore exert its effects through binding to the glucocorticoid receptor. The aim of the present study was to investigate if the GH3 tumour cells and an oestrogen induced pituitary tumours, which also produce GH and Prl, possess specific receptors for progesterone. Both the GH3 tumours and the oestrogen induced pituitary tumour were in fact found to possess cytoplasmatic receptor molecules for progesterone by using the potent progestin R5020 as a marker. Isoelectric focusing revealed one binding component (pH 5.9), which was of protein nature. The binding was of high affinity (KD 2 X 10(-9) mol/l). In the oestrogen induced tumour, the maximal binding was 70 fmol/mg cytosol protein. In female rats with GH3 tumours the binding was 55 fmol/mg cytosol protein. Priming of the animals with 1 mg oestradiol-valerate increased the binding to 116 fmol/mg cytosol protein, whereas very little binding was found in GH3 tumours from rats castrated 7 days before sacrifice. The receptors in the oestrogen induced pituitary tumour and the GH3 tumours exhibited high affinity for R5020 and progesterone, whereas corticosterone had no significant affinity for the receptors. Using exchange assay, it was demonstrated that the cytoplasmic progestin receptors could be translocated to the nucleus after administration of progesterone to the animals. Thus, the presence of specific progesterone receptors, different from the glucocorticoid receptors, strongly indicates that athe effects of progesterone on GH and Prl production are mediated through the progesterone receptors.