Regulation of steroid hydroxylase gene expression in the ovine fetal adrenal gland at 0.4 gestation.
This study was designed to test the hypothesis that ACTH from the fetal pituitary is a major regulator of adrenocortical steroid hydroxylase gene expression in the ovine fetus at 0.4 (60-70 days) of gestation. Pregnant ewes at 0.4 gestation received intravenous infusions of dexamethasone (0.76 mg/h, n = 13) for 48 h. The rationale for this regime was that some of the infused dexamethasone would cross the placenta and act on the fetal pituitary to suppress ACTH release. Control animals received infusions of saline (0.38 ml/h, n = 12) for 48 h. At the end of the infusion period, the animals were killed, umbilical vessel blood taken for ACTH and cortisol analyses, and the fetal adrenal glands taken for assessment of P-450scc, P-450(17 alpha) and P-450c21 levels using the techniques of hybridization histochemistry and RNase protection assay. Dexamethasone treatment decreased maternal and fetal concentrations of ACTH to 29 +/- 10 and < 20 pg/ml, respectively and cortisol concentrations to 3.5 +/- 0.6 and 3.2 +/- 0.8 nmol/l respectively. The adrenal glands from the dexamethasone-treated fetuses exhibited significantly lower levels of mRNA for P-450scc (11% of control) and P-450(17 alpha) (2% of control). These results suggest that ACTH is a major regulator of steroid hydroxylase gene expression and subsequent cortisol biosynthesis in vivo in the ovine fetus at 0.4 gestation.
Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Parkville, Victoria, Australia.
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K
Tangalakis
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R
Crawford
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AC
McFarlane
E M
EM
Wintour
D000311:Adrenal Glands / Q000196:embryology* / Q000201:enzymology; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D005865:Gestational Age; D006854:Hydrocortisone / Q000097:blood; D008431:Maternal-Fetal Exchange; D009693:Nucleic Acid Hybridization; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D012260:Ribonucleases; D012756:Sheep; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics; D013250:Steroid Hydroxylases / Q000235:genetics*
D012333:RNA, Messenger; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D013250:Steroid Hydroxylases; D013254:Steroid 17-alpha-Hydroxylase; D002786:Cholesterol Side-Chain Cleavage Enzyme; D012260:Ribonucleases; D006854:Hydrocortisone