Steroidogenesis of Corticosteroids, Genetic Mutation, and Endocrine Disruption Leading to Adrenal Insufficiency

Abstract

Steroidogenesis, the process by which steroids are synthesized, involves a complex cascade of enzymatic reactions that ultimately produce hormones, such as cortisol and aldosterone. Cortisol is a steroid hormone that plays a critical role in the regulation of various physiological processes, including metabolism, immune response, and stress response. Aldosterone is responsible for blood pressure and water balance. The biosynthesis of cortisol and aldosterone occurs primarily in the adrenal cortex and is processed by a series of enzymatic reactions that convert cholesterol into cortisol and aldosterone. Enzymes include CYP11A1, 3β-hydroxysteroid dehydrogenase 2, CYP11B1, CYP11B2, CYP17A1, and 21-hydroxylase. Mutations or defects in these enzymes can lead to impaired cortisol and aldosterone biosynthesis, thereby resulting in various disorders such as congenital adrenal hyperplasia, adrenal hypoplasia congenita, and familial glucocorticoid deficiency. Endocrine disruptors, such as phthalates, bisphenols, and pesticides, affect adrenal cortex development or steroidogenesis, thereby causing adrenal cortex dysfunction. Understanding the complex process of steroidogenesis involved in cortisol and aldosterone biosynthesis can provide crucial insights into the pathophysiology of adrenal disorders and inform the development of targeted therapies to alleviate the associated symptoms.