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 [125I]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 [125I]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.
Han
S W
SW
Department of Obstetrics and Gynecology, University of Louisville Health Sciences Center, Kentucky 40292, USA.
Lei
Z M
ZM
Rao
C V
CV
D000328:Adult; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D004717:Endometrium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006207:Half-Life; D006801:Humans; D066298:In Vitro Techniques; D007986:Luteinizing Hormone / Q000378:metabolism; D008593:Menopause / Q000378:metabolism; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011974:Receptors, LH / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*
D006063:Chorionic Gonadotropin; D012333:RNA, Messenger; D011974:Receptors, LH; D007986:Luteinizing Hormone