title: Differential expression of placental 11β-hydroxysteroid dehydrogenases in pregnant women with diet-treated gestational diabetes mellitus.
abstract: Fetal exposure to excess glucocorticoid is one of the critical factors for the fetal origins of adult diseases. However, the mechanism of the local regulation of glucocorticoid activity in the human placenta of pregnancies complicated with gestational diabetes mellitus (GDM) has not been fully understood. We investigated placental 11β-hydroxysteroid dehydrogenases (11β-HSDs) expression, and analyzed their relationship with cortisol levels in maternal and umbilical vein. Pregnant women with GDM after diet intervention (n=23) or normal glucose tolerance (NGT, n=22) were studied at the community-based hospital. We collected maternal and umbilical venous cord blood and placental tissues from both groups. Explanted placentas from NGT were cultured with palmitic acid, dexamethasone, insulin or their mixture for 24-h. We examined plasma cortisol, cortisone to cortisol ratio, insulin, the homeostasis model assessment of insulin resistance index (HOMA-IR) and the insulin secretion index. Quantitative real-time PCR, Western blot and immunohistochemical assay were applied for the measurement of 11β-HSD1 and 11β-HSD2 mRNA and protein. GDM had higher maternal cortisol levels, HOMA-IR, insulin secretion index and higher cortisone to cortisol ratio in umbilical vein. No significant change in cortisol levels in umbilical vein and newborn weight was found. GDM placental 11β-HSD1 levels decreased while 11β-HSD2 increased. Treatment of placenta explants from NGT with palmitic acid, dexamethasone, insulin or their combination resulted in a significant drop of 11β-HSD1 and increase in 11β-HSD2. Differential expression of 11β-HSDs in diet-treated GDM placenta provides a protective mechanism for the fetus throughout the adverse environment of pregnancy by limiting excessive exposure of the fetus to glucocorticoid.
authors.affiliation: Institute of Life Sciences, Chongqing Medical University, #1 Yixueyuan Rd., Yuzhong District, Chongqing 400016, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Ma
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
authors.forename: Li
authors.initials: L
authors.lastname: Wu
authors.forename: Jiangchuan
authors.initials: J
authors.lastname: Sun
authors.forename: Zhu
authors.initials: Z
authors.lastname: Yang
authors.forename: Chao
authors.initials: C
authors.lastname: Yu
authors.forename: Pei
authors.initials: P
authors.lastname: Yuan
authors.forename: Xiaoqiu
authors.initials: X
authors.lastname: Xiao
mesh_terms: D042842:11-beta-Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D001724:Birth Weight; D015153:Blotting, Western; D002851:Chromatography, High Pressure Liquid; D017931:DNA Primers; D016640:Diabetes, Gestational / Q000178:diet therapy* / Q000201:enzymology*; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007150:Immunohistochemistry; D007231:Infant, Newborn; D010920:Placenta / Q000201:enzymology*; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D012333:RNA, Messenger; D042842:11-beta-Hydroxysteroid Dehydrogenases; D006854:Hydrocortisone