Endogenous inhibition of the 20 alpha-hydroxysteroid dehydrogenase (EC 1.1.1.149) in the human term placenta in vitro.
Human placental 20 alpha-hydroxysteroid dehydrogenase (20 alpha-HSDH) interconverts progesterone and 20 alpha-dihydroprogesterone (20 alpha-DHP). In this study, an endogenous inhibitor of the cytoplasmic 20 alpha-HSDH isolated from human term placenta is demonstrated. Characterization of the endogenous inhibitor was carried out by adding heat-denatured fractions of the 20 alpha-HSDH enzyme stock solution to the incubations. The aqueous phase of the 20 alpha-HSDH (after diethylether extraction) using 8-fold concentration of the enzyme inhibited the 20 alpha-HSDH activity by 50%. After ultrafiltration of the aqueous phase, this inhibitory effect (50%) was found in the aqueous fraction with a molecular weight above 12,800. No inhibition of the 20 alpha-HSDH was shown using the ether phase or the aqueous ultrafiltrate with a molecular weight below 12,800. The 20 alpha-HSDH was stimulated by human and bovine serum albumins up to 290% and 420% respectively. Bovine serum albumin showed a higher stimulatory effect on the oxidative (420%) than on the reductive (190%) pathway of the 20 alpha-HSDH. Ovalbumin and immunoglobulin G had no effect. The endogenous inhibitor of the cytoplasmic 20 alpha-HSDH isolated from the human term placenta is heat stable (100 degrees C), water soluble, not soluble in diethylether and has a molecular weight above 12,800. The stimulatory effect of serum albumins in 20 alpha-HSDH may be caused by binding and inactivation of the endogenous inhibitor.
D015089:20-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors*; D043607:20-alpha-Hydroxysteroid Dehydrogenase; D003593:Cytoplasm / Q000201:enzymology; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006358:Hot Temperature; D006801:Humans; D008970:Molecular Weight; D010920:Placenta / Q000201:enzymology*; D011247:Pregnancy; D011489:Protein Denaturation; D012709:Serum Albumin / Q000494:pharmacology; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D014462:Ultrafiltration
D012709:Serum Albumin; D012710:Serum Albumin, Bovine; D015089:20-Hydroxysteroid Dehydrogenases; D043607:20-alpha-Hydroxysteroid Dehydrogenase