Progestin modulation of c-fos and prolactin gene expression in the human endometrium.

Objective: To evaluate the influence of the menstrual cycle and the effects of medroxyprogesterone acetate (MPA) on the expression of the protooncogene c-fos and of prolactin (PRL) in the human endometrium in vivo.

Design: Double-blind, placebo-controlled trial.

Setting: Healthy volunteers in an academic research environment.

Patient(s): Regularly cycling women who were not taking hormonal medication.

Intervention(s): Medroxyprogesterone acetate (10 mg/d) or placebo was given for 10 days. Endometrial and blood samples were collected 8–12 hours after the last dose.

Main Outcome Measure(s): Immunohistochemical localization of PRL and c-fos in the endometrium, PRL and c-fos messenger RNA levels in the endometrium, and E₂ and progesterone levels in the serum.

Result(s): Immunoreactive c-fos was concentrated in the nucleus of stromal cells and was observed in a higher proportion of proliferative endometrial specimens compared with secretory specimens from placebo- or MPA-treated patients. The levels of c-fos messenger RNA were greatly reduced in the secretory endometrium regardless of treatment with placebo or MPA, compared with the proliferative endometrium. The c-fos gene expression correlated positively with the serum E₂ levels (r = 0.56) and inversely with the progesterone/E₂ ratio (r = ?0.56). The endometrial PRL gene expression (messenger RNA and protein) was rare in the proliferative samples, increased from the early to the mid and late secretory samples, and was increased markedly after treatment with MPA compared with placebo.

Conclusion(s): The differentiation of secretory endometrium is accompanied by decreased c-fos and increased PRL gene expression. The inhibition of c-fos gene expression may contribute to the antiproliferative effect of progestins on the endometrium.