A premature increase in circulating cortisol suppresses expression of 11beta hydroxysteroid dehydrogenase type 2 messenger ribonucleic acid in the adrenal of the fetal sheep.
We have investigated the effect of intrafetal cortisol administration, before the normal prepartum cortisol surge, on the expression of 11beta hydroxysteroid dehydrogenase (11betaHSD) type 2 mRNA in the fetal adrenal. We also determined whether increased fetal cortisol concentrations can stimulate growth of the fetal adrenal gland or increase expression of adrenal steroidogenic enzymes. Cortisol (hydrocortisone succinate: 2.0-3.0 mg in 4.4 ml/24 h) was infused into fetal sheep between 109 and 116 days of gestation (cortisol infused; n = 12), and saline was administered to control fetuses (saline infused; n = 13) at the same age. There was no effect of cortisol infusion on the fetal adrenal:body weight ratio (cortisol: 101.7 +/- 5.3 mg/kg; saline: 108.2 +/- 4.3 mg/kg). The ratio of adrenal 11betaHSD-2 mRNA to 18S rRNA expression was significantly lower, however, in the cortisol-infused group (0.75 +/- 0.02) compared with the group receiving saline (1.65 +/- 0.14). There was no significant effect of intrafetal cortisol on the relative abundance of adrenal CYP11A1, CYP17, CYP21A1, and 3betaHSD mRNA. A premature elevation in fetal cortisol therefore resulted in a suppression of adrenal 11betaHSD-2. Increased intra-adrenal exposure to cortisol at this stage of gestation is, however, not sufficient to promote adrenal growth or steroidogenic enzyme gene expression.
Ross
J T
JT
Department of Physiology, The University of Adelaide, Adelaide, South Australia 5000, Australia.
McMillen
I C
IC
Adams
M B
MB
Coulter
C L
CL
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000311:Adrenal Glands / Q000033:anatomy & histology / Q000196:embryology* / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D001835:Body Weight; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D004798:Enzymes / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005312:Fetal Blood / Q000378:metabolism*; D006854:Hydrocortisone / Q000097:blood* / Q000494:pharmacology; D006913:Hydroxysteroid Dehydrogenases / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D009929:Organ Size; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D012756:Sheep / Q000196:embryology; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics
D004798:Enzymes; D012333:RNA, Messenger; D000324:Adrenocorticotropic Hormone; D003577:Cytochrome P-450 Enzyme System; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; D013254:Steroid 17-alpha-Hydroxylase; D002786:Cholesterol Side-Chain Cleavage Enzyme; D006854:Hydrocortisone