Microsomal 20 alpha-hydroxysteroid dehydrogenase activity for progesterone in human placenta

Area of Science:

• Reproductive biology
• Steroid metabolism
• Enzymology

Background:

• The enzyme 20 alpha-hydroxysteroid dehydrogenase (20 alpha-HSD) plays a role in steroid metabolism.
• Understanding placental 20 alpha-HSD is vital for comprehending pregnancy maintenance and labor initiation.

Purpose of the Study:

• To investigate the localization and characteristics of placental 20 alpha-HSD activity.
• To elucidate the enzyme's role in progesterone metabolism during human pregnancy.

Main Methods:

• Human placental tissues from various gestational weeks were homogenized and fractionated.
• Enzymatic activity was assessed by incubating fractions with 14C-progesterone and measuring conversion to 20 alpha-dihydroprogesterone.
• Kinetic parameters (Km) and cofactor requirements (NADPH, NADH) were determined.

Main Results:

• The highest 20 alpha-HSD activity was localized in the placental microsomal fraction.
• The Michaelis constant (Km) for progesterone in the microsomal fraction was 4.5 X 10(-6)M.
• Placental microsomal 20 alpha-HSD activity requires both NADPH and NADH and increases with gestational age.
• DHEA-sulfate and dehydroepiandrosterone (DHA) significantly inhibited progesterone metabolism by 20 alpha-HSD.

Conclusions:

• Placental microsomal 20 alpha-HSD is a key enzyme in progesterone metabolism.
• The enzyme's activity is modulated by other steroids produced by the feto-placental unit.
• These findings offer insights into the hormonal regulation of pregnancy continuation and labor initiation.