Hydroxysteroid dehydrogenase

Hydroxysteroid dehydrogenases (HSDs) are a group of enzymes involved in the metabolism of steroids. They play a crucial role in the biosynthesis and degradation of steroid hormones by catalyzing the oxidation and reduction of hydroxysteroids. These enzymes are found in a wide variety of tissues, including the liver, adrenal glands, and gonads, reflecting the broad role of steroid hormones in different physiological processes such as metabolism, immune response, and reproduction.

Function

Hydroxysteroid dehydrogenases are responsible for the interconversion of ketones and alcohol groups in steroid hormones. This biochemical reaction is essential for the activation and inactivation of these hormones. For example, in the cortisol metabolism pathway, the enzyme 11β-hydroxysteroid dehydrogenase converts inactive cortisone into active cortisol, and vice versa, regulating its biological activity. Similarly, in sex steroid metabolism, 17β-hydroxysteroid dehydrogenase converts less active forms of estrogen and testosterone into their more active forms, estradiol and dihydrotestosterone, respectively.

Classification

Hydroxysteroid dehydrogenases are classified based on their substrate specificity and reaction direction. The two main classes are:

• 11β-Hydroxysteroid dehydrogenase (11β-HSD): This class includes two isoforms, 11β-HSD1 and 11β-HSD2, which regulate the local concentrations of active glucocorticoids like cortisol.
• 17β-Hydroxysteroid dehydrogenase (17β-HSD): This class consists of several isoforms that are involved in the metabolism of sex steroids, including the conversion of estrone to estradiol and androstenedione to testosterone.

Clinical Significance

Alterations in the activity of hydroxysteroid dehydrogenases can lead to various diseases. For instance, an overexpression of 11β-HSD1 has been linked to obesity, type 2 diabetes, and metabolic syndrome, due to the excessive activation of cortisol. Conversely, a deficiency in 11β-HSD2 can cause hypertension and hypokalemia by allowing excessive cortisol action in the kidney, a condition known as apparent mineralocorticoid excess syndrome.

In the realm of reproductive health, abnormalities in 17β-HSD can affect sex steroid levels, potentially leading to disorders of sex development and infertility. For example, a deficiency in 17β-HSD type 3 is associated with male pseudohermaphroditism due to impaired testosterone synthesis.

Research Directions

Research on hydroxysteroid dehydrogenases continues to explore their role in health and disease. This includes the development of selective inhibitors or activators as potential therapeutic agents for conditions associated with dysregulated steroid hormone action, such as metabolic diseases and certain types of cancer.

See Also

• Steroid hormone
• Metabolism
• Enzyme
• Cortisol
• Testosterone
• Estrogen