5β-Dihydroprogesterone

5β-Dihydroprogesterone (5β-DHP) is a steroid and, more specifically, a progesterone metabolite. It is formed from progesterone in the body by the enzyme 5β-reductase and is a precursor to the neurosteroid allopregnanolone.

Structure and Synthesis

5β-Dihydroprogesterone is a C21 steroid with a pregnane skeleton. It is synthesized from progesterone by the action of the enzyme 5β-reductase. This enzyme reduces the Δ4-3-keto group in the A ring of progesterone to form 5β-DHP. The reaction is NADPH dependent and occurs in many tissues, including the liver, brain, and placenta.

Biological Activity

5β-Dihydroprogesterone is a potent progestogen, meaning it has the ability to bind to and activate the progesterone receptor. It is also a precursor to the neurosteroid allopregnanolone, which has anxiolytic, antidepressant, proconvulsant, and sedative effects. Allopregnanolone is synthesized from 5β-DHP by the action of the enzyme 3α-hydroxysteroid dehydrogenase.

Clinical Significance

Abnormal levels of 5β-DHP have been associated with various medical conditions. For example, elevated levels have been found in women with polycystic ovary syndrome (PCOS), possibly due to increased activity of 5β-reductase. Conversely, reduced levels of 5β-DHP have been observed in individuals with major depressive disorder (MDD), suggesting a potential role in the pathophysiology of this condition.

See Also

• Progesterone
• 5β-Reductase
• Allopregnanolone
• Neurosteroid
• Polycystic ovary syndrome
• Major depressive disorder