Effects of cannabinoids on macromolecular synthesis in isolated spermatogenic cells

Effects of delta 9-tetrahydrocannabinol (THC), cannabinol (CBN) and cannabidiol (CBD) (1, 3 or 5 microM for 2 h) on macromolecular synthesis were investigated in homogeneous populations of pachytene spermatocytes and round spermatids obtained from CD-1 mice. Incorporation of 3H-uridine into the acid-insoluble fraction was used as an index of RNA synthesis. Treatment of pachytene spermatocytes with 5 microM THC, CBN and CBD reduced radioactive incorporation by 81%, 62% and 67%, respectively, compared to vehicle (dimethylsulfoxide) controls. Treatment of round spermatids with 5 microM THC, CBN and CBD reduced radioactive incorporation by 54%, 61% and 63%, respectively, compared to controls. In addition to reduction of radioactive incorporation into the acid-insoluble fraction, there was also reduction in the acid-soluble fraction not comparable in magnitude to the reduction in the acid-insoluble fraction. Pachytene spermatocytes and round spermatids isolated from THC-treated mice (10 and 20 mg/kg) showed no reduction in macromolecular synthesis compared to cells isolated from vehicle-treated mice. Suppression of macromolecular synthesis induced by in vitro cannabinoid treatment is discussed in terms of membrane-mediated interference with cell metabolism.