Regulation of prolactin synthesis by estrogen

There is an increasing body of evidence implicating estradiol in the regulation of prolactin synthesis. We have recently demonstrated that treatment of rats with estradiol specifically increased the incorporation of precursors into prolactin and led to the accumulation of preprolactin mRNA. These effects of estradiol could be due either to a direct action on the pituitary or to an indirect effect mediated by the hypothalamus. To distinguish between these possibilities, we studied the response of dispersed rat pituitary cells maintained in culture. We found that cultured pituitary cells respond to estradiol by increased incorporation of precursors into prolactin but not into the bulk of other cellular proteins. The rate of increase in prolactin synthesis is dose dependent, reaching maximal levels in the physiological range of estradiol. At a concentration of 10^-9M, estradiol, estriol and diethylstilbestrol are stimulatory whereas androgens, progesterone and cortisone have no significant effect. Exposure of cells to 10^-8M, estradiol results in a 500% stimulation of prolactin synthesis after 7 days of culture. The time course and magnitude of response to estradiol in cultured pituitary cells is comparable to the response seen in vivo. Our findings indicate that estradiol can stimulate prolactin synthesis through a direct action on the pituitary.