Progesterone Suppression of Estrogen-Stimulated Prolactin Secretion and Estrogen Receptor Levels in Rat Pituitary Cells*

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Abstract
The effects of progesterone, testosterone, corticosterone,and TRH on estrogen-induced PRL synthesis andcytoplasmic estrogen receptor levels were studied in a clonalstrain of rat pituitary tumor cells (GH3). PRL synthesis wasmeasured as the amount of hormone which accumulated in theculture medium (micrograms per mg cell protein/24 h), andreceptor levels were measured as specific [3H]estradiol bindingin the GH3 cells (picomoles per mg cell protein). 17Β-Estradiol (10-8M) stimulated PRL synthesis 2.1-fold, while progesterone (10-6 M) and corticosterone (10-6 M) bothdecreased PRL synthesis to about 0.9 times control levels. Testosterone(10-6 M) and TRH (3 x 10-7 M) increased PRL synthesis1.2- and 1.8-fold, respectively. The combined treatmentwith 17Β-estradiol plus progesterone increased PRL synthesis1.2-fold, while the simultaneous treatment with either 17Β8-estradiol and corticosterone or 17Β-estradiol and testosterone stimulated PRL synthesis to values not significantly different from those in cultures treated with 17/8-estradiol alone. In contrast, the stimulatory effects of 17Β-estradiol and TRH were additive. The antagonistic effects of progesterone on estrogen-induced PRL synthesis were not due to competition with 17Β-estradiol for binding to the estrogen receptor. Treatment with progesterone, but not with the other hormones, reduced estrogen receptor levels in the GH3 cells, but did not change the binding affinity between [3H]estradiol and its receptor. The inhibitory effect of progesterone was significant (P < 0.03) at 10-10 M and maximal at 10-6 M, decreasing specific [3H]estradiol binding from 0.283 ± 0.007 in control cultures to 0.055 ± 0.006 (mean ± SE) pmol/mg cell protein. The progesterone effect was detectable after 2 days and maximal after 4 days of treatment. These data suggest strongly that progesterone inhibits estrogen- induced PRL synthesis by decreasing the number of available receptor sites.