Regulation of 17-beta hydroxysteroid dehydrogenase type 2 in human placental endothelial cells.
17-beta hydroxysteroid dehydrogenase type 2 (HSD17B2) oxidizes estradiol to estrone, testosterone to androstenedione, and 20 alpha-dihydroprogesterone to progesterone. HSD17B2 is highly expressed in human placental tissue where it is localized to placental endothelial cells lining the fetal compartment. The aim of this study was to investigate the effects of potential regulatory factors including progesterone, estradiol, and retinoic acid (RA) onHSD17B2 expression in primary human placental endothelial cells in culture.HSD17B2 mRNA expression was not regulated by progesterone, the progesterone agonist R5020, or estradiol treatment. RA significantly induced HSD17B2 mRNA levels and enzyme activity in a dose- and time-dependent manner. Maximal stimulation occurred at Hour 48 at an RA concentration of 10(-6) M. Both retinoic acid receptor alpha (RARA) and retinoid X receptor alpha (RXRA) were readily detected by immunoblotting in isolated placental endothelial cells. RNA interference directed against RARA or RXRA led to reduced basal levels of HSD17B2 mRNA levels and significantly abolished RA-stimulated HSD17B2 expression. Together, these data indicate that regulation of HSD17B2 mRNA levels and enzymatic activity by RA in the placenta is mediated by RARA and RXRA.
Su
Emily J
EJ
Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Northwestern University, Chicago, Illinois 60611, USA.
Cheng
You-Hong
YH
Chatterton
Robert T
RT
Lin
Zhi-Hong
ZH
Yin
Ping
P
Reierstad
Scott
S
Innes
Joy
J
Bulun
Serdar E
SE
D015067:17-Hydroxysteroid Dehydrogenases / Q000096:biosynthesis* / Q000235:genetics; D042783:Endothelial Cells / Q000201:enzymology; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005455:Fluorescent Antibody Technique; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D015151:Immunoblotting; D010920:Placenta / Q000166:cytology / Q000201:enzymology*; D011374:Progesterone / Q000494:pharmacology*; D045167:Progesterone Congeners / Q000494:pharmacology; D011397:Promegestone / Q000494:pharmacology*; D034622:RNA Interference; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D018168:Receptors, Retinoic Acid / Q000096:biosynthesis / Q000235:genetics; D000072482:Retinoic Acid Receptor alpha; D047490:Retinoid X Receptor alpha / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D045167:Progesterone Congeners; C000607071:RARA protein, human; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D047490:Retinoid X Receptor alpha; D011374:Progesterone; D004958:Estradiol; D011397:Promegestone; D015067:17-Hydroxysteroid Dehydrogenases; C044256:3 (or 17)-beta-hydroxysteroid dehydrogenase