Down-regulation of LH/hCG receptor in rat cultured granulosa cells.
Initial experiments established the experimental conditions necessary for the induction of LH receptor mRNA down-regulation in granulosa cells isolated from diethylstilbestrol (DES)-primed immature rats. LH/hCG receptor mRNA was first induced in granulosa cells by incubating them for 24 h with FSH. Exposure of granulosa cells to a second dose of gonadotropin caused a decrease in LH/hCG receptor mRNA and binding levels after 4 h. This effect was transient, by 12 h the mRNA levels had returned to control levels, and by 24 h the mRNA levels were higher than the control. To evaluate the ability of cAMP to down-regulate the receptor, cells were exposed to 8-Br-cAMP. The pattern of sustained decrease in LH/hCG receptor mRNA levels seen with 8-Br-cAMP was similar to that with gonadotropins. The presence of activin with FSH or hCG is more effective than FSH or hCG alone in inducing LH/hCG receptor down-regulation in rat granulosa cells. The LH/hCG receptor mRNA levels decreased in a dose-dependent manner in the presence of increasing concentrations (30-100 ng/ml) of activin with FSH. These observations indicate that an increase in cAMP causes down-regulation of LH/hCG receptor mRNA and contributes to the effect of FSH and hCG, whereas basal cAMP activity is required for LH/hCG receptor mRNA expression.
Kishi
H
H
Department of Obstetrics and Gynecology, Gunma University School of Medicine, Maebashi, Japan.
Minegishi
T
T
Tano
M
M
Abe
Y
Y
Ibuki
Y
Y
Miyamoto
K
K
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D028341:Activins; D000818:Animals; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology; D006107:Granulosa Cells / Q000378:metabolism*; D007265:Inhibins / Q000494:pharmacology; D007700:Kinetics; D015347:RNA Probes; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D011974:Receptors, LH / Q000096:biosynthesis*; D014158:Transcription, Genetic
D006063:Chorionic Gonadotropin; D015347:RNA Probes; D012333:RNA, Messenger; D011974:Receptors, LH; D028341:Activins; D015124:8-Bromo Cyclic Adenosine Monophosphate; D007265:Inhibins; D005640:Follicle Stimulating Hormone; D000242:Cyclic AMP