The Sensitizing Effect of Estrogens and Catechol Estrogen on Cultured Pituitary Cells to Luteinizing Hormone-Releasing Hormone: Its Antagonism by Progestins*

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Abstract
The direct effect of steroid hormones upon LHRH-induced LH release was tested in cultured pituitary gonadotrophs. Anterior pituitary cells from adult ovariectomized rats were cultured for 2 days in the presence and absence of estrone (E1), 17β-estradiol (E2), estriol (E3), 2-hydroxyestrone (2-OHE1), 2-hydroxyestradiol (2-OHE2), progesterone (P), and 20α-dihydroprogesterone (20α-OHP). The cells were then washed and incubated for 3 h with graded doses of LHRH (10-12-10-6 M) and the LH released into the media was measured by RIA. A dose-related increase in LH secretion was observed with increasing concentrations of LHRH and, in control cultures, the half-maximal effective dose (ED50) of LHRH was 1.9 ± 0.6 × 10-9 M. Pretreatment with Ei or E2 (10-10-10-8 M) sensitized gonadotrophs to LHRH and caused a 10-fold decrease in the ED50. 2-OHE2 also exhibited a sensitizing effect, but it was less effective than E2 (2-OHE2: 10-10 M, no effect; 10-8 M, ED50, 2.5 ± 0.5 × 10-10 M). NO sensitizing effect was observed with E3 (10 8 M) and 2-OHE1 (10-8 M). P alone (10-8 and 10-8 M) did not affect the ED50 of LHRH in LH release; however, when pituitary cells were incubated with a combination of P and E2 (10-9 M), the sensitizing effect of E2 was antagonized. 20α-OHP (10-6 M) did not change the ED50 of LHRH, but decreased maximal LH production and antagonized the E2-induced sensitization to LHRH. Measurement of the intracellular content of LH together with the amount of LH released indicates that total LH synthesis was not affected by estradiol or P treatment. This study demonstrates the relative potency of estrogens and catechol estrogens (E2 = E1 > 2-0HE1; E3 and 2-OHE1, no effect) in sensitizing gonadotrophs to LHRH and shows that the sensitization effect of E2 is antagonized by P and 20α-OHP.