title: Changes in human placental 5alpha-reductase isoenzyme expression with advancing gestation: effects of fetal sex and glucocorticoid exposure.
abstract: 5alpha-reduced steroids, including allopregnanolone, suppress neuronal activity and can have neuroprotective effects in the fetus. 5alpha-reductases in the placenta may contribute precursors to brain allopregnanolone synthesis. Preterm birth and glucocorticoids, administered for fetal lung maturation or for maternal asthma, may influence reductase expression. The aims of the present study were to evaluate placental 5alpha-reductase isoform expression during late gestation and to examine fetal sex differences and the effects of glucocorticoid therapies on the expression of these enzymes. Expression of the two 5alpha-reductase isoenzymes was measured in placental samples, whereas cortisol concentrations were measured in cord blood, from two cohorts. The first cohort consisted of women who delivered preterm and received betamethasone treatment (n=41); the second cohort consisted of women who delivered at term and were either healthy controls (n=30) or asthmatics who had used glucocorticoids (n=24). Placental expression of both isoenzymes increased with advancing gestation and there were marked sex differences in levels of 5alpha-reductase I (P<0.05), but not of 5alpha-reductase II. The expression of both enzymes was positively correlated with cortisol levels (P<0.05), but there was no effect of recent glucocorticoid exposure. These findings suggest that the preterm neonate may have lower developmental exposure to 5alpha-reduced steroids and may lack steroid-mediated neuroprotection depending on fetal sex.
authors.affiliation: Mothers and Babies Research Centre and School of Biomedical Sciences, John Hunter Hospital Campus, University of Newcastle, Callaghan, NSW 2308, Australia.
authors.forename: Thi T
authors.initials: TT
authors.lastname: Vu
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Hirst
authors.forename: Michael
authors.initials: M
authors.lastname: Stark
authors.forename: Ian M R
authors.initials: IM
authors.lastname: Wright
authors.forename: Hannah K
authors.initials: HK
authors.lastname: Palliser
authors.forename: Nicolette
authors.initials: N
authors.lastname: Hodyl
authors.forename: Vicki L
authors.initials: VL
authors.lastname: Clifton
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism*; D000280:Administration, Inhalation; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use; D001623:Betamethasone / Q000627:therapeutic use; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D005865:Gestational Age; D005938:Glucocorticoids / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D010920:Placenta / Q000187:drug effects* / Q000201:enzymology*; D011247:Pregnancy; D047928:Premature Birth / Q000097:blood / Q000188:drug therapy / Q000201:enzymology*; D012737:Sex Factors
chemical_list: D018927:Anti-Asthmatic Agents; D005938:Glucocorticoids; D001623:Betamethasone; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; C476566:steroid-5alpha-reductase type 1; C476567:steroid-5alpha-reductase type 2; D006854:Hydrocortisone