Effects of cannabinoids on progesterone release in cultures of rat luteal cells.
This study investigated the direct effects of tetrahydrocannabinols (THC) on progesterone release by cultured rat luteal cells, as a function of dose and time. During a 24-h incubation, the level of progesterone in the culture medium was decreased by 35% and 60% in the presence of 1 microM 11-OH-delta 9-THC and 8 beta-OH-delta 9-THC, respectively, when compared with control cultures. Dose-response analysis revealed that 8 beta-OH-delta 9-THC inhibited progesterone levels at 0.1 microM but not at lower concentrations. The action of 8 beta-OH-delta 9-THC was rapid in onset and a significant effect could be observed as early as 2 h following the addition of the cannabinoid. While luteinizing hormone (LH, 1 microgram/ml) significantly enhanced progesterone release in the culture medium over the respective control levels, this action of LH was dramatically suppressed by the concomitant presence of 8 beta-OH-delta 9-THC at 2, 4 and 24 h in separate experiments. Moreover, the increase in the level of progesterone in the culture medium induced by 8-bromo-cyclic AMP was also attenuated by the concomitant presence of 8 beta-OH-delta 9-THC in the cultures. These results further substantiate a direct action of cannabinoids on the steroidogenic function of the corpus luteum, and that it involves at least some step(s) distal to the LH-sensitive adenylate cyclase system.
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D002186:Cannabinoids / Q000494:pharmacology*; D002478:Cells, Cultured; D003338:Corpus Luteum / Q000187:drug effects* / Q000378:metabolism; D013759:Dronabinol / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D007986:Luteinizing Hormone / Q000494:pharmacology; D011374:Progesterone / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D002186:Cannabinoids; D015124:8-Bromo Cyclic Adenosine Monophosphate; C001427:11-hydroxy-delta(9)-tetrahydrocannabinol; C033935:8-hydroxy-delta(9)-tetrahydrocannabinol; D011374:Progesterone; D013759:Dronabinol; D007986:Luteinizing Hormone