3ò-Hydroxysteroid dehydrogenase/ÃÂ<sup>5-4</sup> isomerase (3ò-HSD) () is an enzyme that catalyzes the biosynthesis of the steroid progesterone from pregnenolone, 17ñ-hydroxyprogesterone from 17ñ-hydroxypregnenolone, and androstenedione from dehydroepiandrosterone (DHEA) in the adrenal gland. It is the only enzyme in the adrenal pathway of corticosteroid synthesis that is not a member of the cytochrome P450 family. It is also present in other steroid-producing tissues, including the ovary, testis and placenta. In humans, there are two 3ò-HSD isozymes encoded by the HSD3B1 and HSD3B2 genes.
3ò-HSD is also known as delta ÃÂ<sup>5-4</sup>-isomerase, which catalyzes the oxidative conversion of ÃÂ<sup>5</sup>-3ò-hydroxysteroids to the ÃÂ<sup>4</sup>-3-keto configuration and is, therefore, essential for the biosynthesis of all classes of hormonal steroids, namely progesterone, glucocorticoids, mineralocorticoids, androgens, and estrogens.
The 3ò-HSD complex is responsible for the conversion of:
3ò-HSD belongs to the family of oxidoreductases, to be specific, those acting on the CH-OH group with NAD<sup>+</sup> or NADP<sup>+</sup> as acceptor. This enzyme participates in C21-steroid hormone metabolism and androgen and estrogen metabolism.
3ò-HSD catalysis|catalyzes the chemical reaction:
The two substrates of this enzyme are 3ò-hydroxy-ÃÂ<sup>5</sup>-steroid and NAD<sup>+</sup>. Its products are 3-oxo-ÃÂ<sup>5</sup>-steroid, NADH, and H<sup>+</sup>.
An example with oxidation and simultaneous double bond isomerism is the conversion of pregnenolone to progesterone:
Humans express two 3ò-HSD isozymes, HSD3B1 (type I) and HSD3B2 (type II). The type I isoenzyme is expressed in placenta and peripheral tissues, whereas the type II 3ò-HSD isoenzyme is expressed in the adrenal gland, ovary, and testis.
The systematic name of this enzyme class is 3ò-hydroxy-ÃÂ<sup>5</sup>-steroid:NAD<sup>+</sup> 3-oxidoreductase. Other names in common use include:
3ò-HSD is potently inhibited by azastene, cyanoketone, epostane, and trilostane. Medroxyprogesterone acetate and medrogestone are weak inhibitors of 3ò-HSD which may substantially inhibit it at high dosages.
A deficiency in the type II form through mutations in HSD3B2 is responsible for a rare form of congenital adrenal hyperplasia. No human condition has yet been linked to a deficiency in the type I enzyme. Its importance in placental progesterone production expression suggests that such a mutation would be embryonically lethal.
The fetal adrenal cortex lacks expression of the enzyme early on, thus mineralocorticoids (e.g. aldosterone) and glucocorticoids (e.g. cortisol) cannot be synthesized. This is significant because cortisol induces type II pneumocytes of the lungs to synthesize and secrete pulmonary surfactant; without pulmonary surfactant to reduce the alveolar surface tension, premature neonates may die of neonatal respiratory distress syndrome. If delivery is unavoidable (e.g. because of placental abruption, or pre-eclampsia/HELLP syndrome), then glucocorticoids (e.g. cortisol) can be administered.