Relationship between estradiol, ergocryptine, and thyroid hormone: Effects on prolactin synthesis and prolactin messenger ribonucleic acid levels

The effects of combinations of estradiol, ergocryptine, and T₃ on PRL synthesis and PRL mRNA levels in monolayer cultures of pituitary cells have been investigated. Incubation of pituitary cells with [³⁵S]methionine, followed by analysis of the newly synthesized proteins on a polyacrylamide gel, suggested that estradiol blocked the ability of ergocryptine to inhibit PRL synthesis, but that estradiol did not affect the ability of T₃ to inhibit PRL synthesis. Quantitative studies utilizing immunoprecipitation of newly synthesized PRL demonstrated that PRL synthesis was reduced to 52% of control in ergocryptine-treated cells and returned to 83% of control in cells treated with ergocryptine plus estradiol. In the same experiment, T₃ treatment reduced PRL synthesis to 50% of control, and PRL synthesis remained at 50% of control values after treatment with T₃ plus estradiol. A concentration of 0.1 nM T₃, which had little effect by itself, augmented the ability of ergocryptine to inhibit PRL synthesis, even in the presence of estradiol. There was a very good correspondence between changes in PRL synthesis and PRL mRNA levels after treatment with combinations of estradiol, ergocryptine, and T₃. Thus, the effects of hormonal interactions on PRL synthesis are probably mediated by changes in the concentration of PRL mRNA. Although, estradiol treatment did not stimulate PRL synthesis in cells treated with 10 nM T₃ cells treated with thyroid hormone contained estradiol receptors. In fact, cells treated with 10 nM T₃ were found to have approximately twice as much nuclear estradiol-binding capacity as control cells. These findings demonstrate that estradiol can block the dopaminergic- but not the thyroid hormone-, induced inhibition of PRL synthesis and suggest that the interaction of all three of these hormones may be important in the physiological regulation of PRL production.