Homologous down-regulation of luteinizing hormone chorionic gonadotropin receptors by increasing the degradation of receptor transcripts in human uterine endometrial stromal cells

We investigated the possible homologous down-regulation of LH/hCG receptors in human uterine endometrial stromal cells. The cells contained a major 4.3-kilobase (kb) and minor 3.6-kb, 2.4-kb, 1.8-kb, and 1.0-kb transcripts of receptors and an 80-kDa receptor protein that can bind [I-125]hCG. Culturing these cells with increasing concentrations of highly purified hCG resulted in a dose-dependent significant decrease in steady-state levels of all the receptor transcripts, the 80-kDa receptor protein, and [I-125]hCG binding as compared to the control values. The hCG effect was hormone specific and required the conformation of native hormone. The decrease in steady-state receptor transcript levels by hCG was not due to a decrease in the transcription rate of the LH/hCG receptor gene. It was rather due to a significant decrease in the half-life of receptor transcripts from 40.1 +/- 12.4 h in the control to 13.3 +/- 3.6 h after treatment. The homologous down-regulation observed in the present study may potentially explain low endometrial receptor levels in the postmenopausal human endometrium.