The suppressive effect of delta-1-tetrahydrocannabinol on the steroidogenic activity of rat granulosa cells in culture.
In previous study the major psychoactive ingredient of marihuana (delta 1-THC) has been shown to inhibit ovarian prostaglandin synthesis when administered to normally cycling rats in the early afternoon of proestrus. These results suggested a direct suppressive effect of the drug on the ovary. The purpose of this study was to evaluate the effect of delta 1-THC on steroidogenesis in granulosa cells (GC) in vitro. Incubation of GC with delta 1-THC (10-50 microM) effectively inhibited LH-stimulatable progestin production. This suppressive effect was not abolished by washing the cells after 24 h of culture in the presence of delta 1-THC, indicating the irreversible nature of the blocking effect of delta 1-THC. By contrast, estradiol production following incubation of GC with testosterone (1 microgram/ml) was not inhibited by similar concentrations of delta 1-THC, thus suggesting that delta 1-THC does not inhibit aromatase activity in GC. In addition, delta 1-THC was shown to inhibit cAMP production as well as 125I-hCG binding capacity to GC. Administration of 8-Br-cAMP did not abolish the delta 1-THC-induced block, suggesting that the drug probably acts distal to the cAMP site of action.
D004092:20-alpha-Dihydroprogesterone / Q000096:biosynthesis; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000378:metabolism; D000242:Cyclic AMP / Q000494:pharmacology; D013759:Dronabinol / Q000494:pharmacology*; D004958:Estradiol / Q000096:biosynthesis; D005260:Female; D006107:Granulosa Cells / Q000187:drug effects* / Q000378:metabolism; D011372:Progestins / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains
D006063:Chorionic Gonadotropin; D011372:Progestins; D004092:20-alpha-Dihydroprogesterone; D015124:8-Bromo Cyclic Adenosine Monophosphate; D004958:Estradiol; D013759:Dronabinol; D000242:Cyclic AMP