REGULATION OF RAT MINERALOCORTICOID RECEPTOR EXPRESSION IN NEURONS BYPROGESTERONE

We have studied the effects of progesterone on the transcription of th e mineralocorticoid receptor (MR) gene in neurons in vitro and in vivo . Progesterone treatment caused a 2.5-fold increase in activity of the MR promoter in transiently transfected N2A neuroblastoma cells. Simil arly, MR promoter activity in GH(3) pituitary cells was increased 2-fo ld after treatment with the specific progesterone receptor agonist R50 20, with an even greater induction after priming with 17 beta-estradio l. Progesterone treatment also produced a dose-dependent increase in M R messenger RNA (mRNA) levels in primary hippocampal neuron cultures. In vivo, chronic administration of progesterone to estrogen-primed adr enalectomized/ovariectomized rats significantly increased MR mRNA leve ls in all hippocampal subfields, as determined by semiquantitative in situ hybridization histochemistry. Whereas chronic estradiol treatment decreased MR mRNA levels in the hippocampus, progesterone administrat ion in the absence of estradiol priming was without any effect. These results indicate that 1) progesterone increases MR mRNA levels in vitr o and in vivo; 2) the stimulatory effects of progesterone are at least partially mediated by induction of MR promoter activity; and 3) estro gen priming is essential for the effect of progesterone upon MR mRNA i n vivo. Further, they suggest the possibility of heterologous regulati on of corticosteroid receptors in the brain, whereby the responsivenes s of the limbic-hypothalamo-pituitary-adrenal system to corticosteroid s may be modulated.