The role of prostaglandins, cyclic nucleotides and tricarboxylic acids in the regulation of the human placental 20 alpha-hydroxysteroid dehydrogenase in vitro.
The in vitro effect of non-steroidal regulators (prostaglandins, cyclic nucleotides and tricarboxylic acids) on the cytoplasmic 20 alpha-hydroxysteroid dehydrogenase (20 alpha-HSDH, EC 1.1.1.149) isolated from human early gestational and term placentas was investigated. When prostaglandins (PG) were tested at 100 microM concentrations, an inhibition of the human placental 20 alpha-HSDH by PGE1 (80% inhibition), PGE2 (70%), PGF1 alpha (40%) PGF2 alpha (30%) and 13,14-dihydro-15-keto-PGF2 (PGFM) (20%) was observed. This effect was shown to be dose-dependent. The I50 (concentration at 50% inhibition) was determined for PGE1 and PGE2 to be 11 microM and 38 microM, respectively. No effect on the activity of the 20 alpha-HSDH could be demonstrated for PGI2 and its stable metabolite 6-keto-PGF1 alpha, for the cyclic nucleotides (dbcAMP, dbcGMP) and for the tricarboxylic acids (citrate, ketoglutarate, lactate, malonate, pyruvate and succinate) when added to the incubation at 100 microM concentration. The 20 alpha-HSDH isolated from early gestational and term placentas did not respond differently to the substances tested. These results suggest that prostaglandins can have a direct, dose-dependent effect on the isolated human placental 20 alpha-HSDH without cyclic nucleotides as intermediates and thereby play a role in the regulation of human progesterone synthesis and metabolism during pregnancy and near term.
D015089:20-Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D000527:Alprostadil; D003994:Bucladesine / Q000494:pharmacology; D015232:Dinoprostone; D005260:Female; D005865:Gestational Age; D006801:Humans; D009712:Nucleotides, Cyclic / Q000502:physiology*; D010920:Placenta / Q000201:enzymology*; D011247:Pregnancy; D011453:Prostaglandins / Q000502:physiology*; D011458:Prostaglandins E / Q000378:metabolism; D014233:Tricarboxylic Acids / Q000502:physiology*
D009712:Nucleotides, Cyclic; D011453:Prostaglandins; D011458:Prostaglandins E; D014233:Tricarboxylic Acids; D003994:Bucladesine; D015089:20-Hydroxysteroid Dehydrogenases; D000527:Alprostadil; D015232:Dinoprostone