Inhibition of luteinizing hormone-human chorionic gonadotropin binding by retinoids in a Leydig cell line.
Treatment of K9 mouse Leydig cells with 3 x 10(-6) M retinol (R) and retinoic acid (RA) resulted in 75% and 65% reduction of 125I-labeled hCG binding respectively, when assayed at 35 degrees C. This effect was dose-dependent and was first detected 12 h after initiation of treatment: it was maximal at 48 h for RA. R and RA had no significant effect on the rate of internalization and degradation of 125I-hCG as measured by disappearance of acid-releasable (i.e. surface-bound) radioactivity from the cells and by the appearance of trichloracetic acid-soluble label in the medium. When exposed to increasing concentrations of hCG for 24 h, both retinoid-treated and control cells 'down-regulated' their gonadotropin receptors with the same dose-dependent pattern. The kinetics of reappearance of the receptors was similar for retinoid-treated and control cells, but for treated cells the maximal number of receptors reinitiated at 24 h never exceeded 40% of the values observed with control cells. Scatchard plot analysis confirmed a decrease in hCG receptor number from approximately 26,000 to approximately 6400 and approximately 3500 sites per cell after R and RA treatment. Kd values for 125I-hCG binding were 2 x 10(-10) M, 7.3 x 10(-11) M and 6.9 x 10(-11) M for control, R- and RA-treated cells respectively. On the basis of our data it is likely that retinoid-induced reduction in 125I-hCG binding to K9 Leydig cells is due to decreased receptor synthesis.
Lefèvre
A
A
Institut National de la Santé et de la Recherche Médicale, Unité 293, Montrouge, France.
Astraudo
C
C
Finaz
C
C
D000818:Animals; D002455:Cell Division; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000037:antagonists & inhibitors*; D015536:Down-Regulation; D004705:Endocytosis; D007700:Kinetics; D007985:Leydig Cells / Q000166:cytology / Q000378:metabolism*; D007986:Luteinizing Hormone / Q000037:antagonists & inhibitors*; D008297:Male; D051379:Mice; D011485:Protein Binding; D011974:Receptors, LH / Q000037:antagonists & inhibitors; D014212:Tretinoin / Q000494:pharmacology*; D014801:Vitamin A / Q000494:pharmacology*
D006063:Chorionic Gonadotropin; D011974:Receptors, LH; D014801:Vitamin A; D014212:Tretinoin; D007986:Luteinizing Hormone