The effects of delta-9 tetrahydrocannabinol (THC) on granulosa cell viability, apoptosis, and gene expression

This thesis investigates the effects of the psychoactive component of cannabis, delta-9 tetrahydrocannabinol (THC) on bovine in vitro granulosa cell viability, apoptosis, and stress response pathway. 11βHSD1-2 convert cortisol into active and inactive forms. Upon cortisol activation, the glucocorticoid receptor (GR) translocates to the nucleus to regulate transcription. MAPK8-9 enhance GR nuclear export and terminate GR-mediated transcription. Heat shock protein 70 and 90 (HSP70, HSP90) are involved in both THC and cortisol pathways. This study hypothesized that THC counteracts cortisol’s effects by modulating 11βHSDs, increasing GR nuclear export and oversaturating HSPs. Cell viability and apoptosis was assessed in response to THC at clinically relevant doses. Gene expression was analyzed in response to THC and cortisol treatments during culture. The experimental data revealed a potential ability for THC to reduce cortisol signalling in GCs. No effect of THC on cell viability and apoptosis was revealed.