Disruption of Androgen Metabolism, Regulation and Effects: Involvement of Steroidogenic Enzymes

The thesis explored the disruption of androgen metabolism and regulation through steroidogenic enzymes. The first study found that anabolic androgenic steroids (ASS), specifically fluoxymesterone, inhibited the enzyme 11beta-HSD2, potentially leading to cardiovascular issues due to cortisol-induced mineralocorticoid receptor activation. The second study examined androgen metabolism in Leydig cells, revealing that BLTK-1 cells use an alternative "back-door" pathway for androstenedione metabolism, unlike MA-10 cells. The third study investigated the transcriptional regulation of the HSD17B3 promoter, identifying TNF-alpha's role in activating this promoter via the p38 MAPK pathway, linking inflammation to increased testosterone and tumor growth. Additionally, it suggested that organotins might activate the HSD17B3 promoter, indicating pro-androgenic effects. These findings highlighted species differences and the complexity of steroidogenesis pathways.