Gonadotropin α Inhibitors

Chemical inhibitors of Gonadotropin α act by disrupting the synthesis of steroid hormones, which are the end products that Gonadotropin α stimulates. Trilostane, operating as an inhibitor of 3β-hydroxysteroid dehydrogenase, hinders the conversion of precursors into active steroids, thus indirectly diminishing Gonadotropin α's role in promoting steroidogenesis. Aminoglutethimide exerts its inhibitory effects by blocking the enzyme P450scc, which catalyzes the initial step of converting cholesterol into pregnenolone, a precursor for all steroid hormones. Consequently, this action attenuates the stimulatory effect of Gonadotropin α on steroid hormone production. Ketoconazole, although primarily known as an antifungal, also disrupts steroid synthesis by inhibiting CYP17A1, an enzyme critical for the production of androgens and estrogens, thereby counteracting the biological activity of Gonadotropin α.

Further down the steroidogenic pathway, metyrapone selectively targets 11β-hydroxylase, crucial for cortisol synthesis, while etomidate and osilodrostat also inhibit this enzyme, leading to altered adrenal hormone profiles and indirectly suppressing the functional activity of Gonadotropin α. Mitotane, with its multifaceted effects on steroidogenesis, can lead to a broad reduction in adrenal steroid output, which falls under the regulatory domain of Gonadotropin α. Aromatase inhibitors such as exemestane, letrozole, and anastrozole reduce estrogen levels by preventing the conversion of androgens into estrogens, a key process that Gonadotropin α is known to stimulate. Consequently, these inhibitors can suppress the functional aspects of Gonadotropin α related to estrogen production. Lastly, finasteride disrupts the conversion of testosterone to dihydrotestosterone by inhibiting 5α-reductase, thus altering the androgen milieu that is tightly regulated by Gonadotropin α, leading to a downregulation of the protein's functional activity.