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1 Obstetrics and Gynecology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
2 Center for Perinatal Biology, Loma Linda University, Loma Linda, CA, USA
3 Obstetrics and Gynecology, University of Wisconsin, Madison, WI, USA
* To whom correspondence should be addressed. E-mail: cducsay{at}som.llu.edu.
We previously demonstrated elevated basal plasma ACTH1-39 concentrations in long-term hypoxic (LTH) fetal sheep. This study was designed to determine if the expression of genes regulating cortisol biosynthesis was altered following LTH. Pregnant ewes were maintained at high altitude (3,820 m) from day 30 of gestation to near term when the animals were transported to the laboratory. Reduced PO2 was maintained by nitrogen infusion through a maternal tracheal catheter. On day 137-141, fetal adrenal glands were collected from LTH and normoxic control (CONT) fetuses. Real time (qRT) PCR was used to quantify mRNA for steroidogenic acute regulatory protein (StAR), 17 
hydroxylase (CYP17), 21 hydroxylase (CYP21), cholesterol side-chain cleavage (CYP11A1), 3 
hydroxysteroid dehydrogenase type II (HSD3B2) and the ACTH receptor. Messenger RNA was also analyzed by slot blot hybridization. We also quantified mRNA for transcription factors necessary for adrenocortical development; steroidogenic factor 1 (SF-1) and dosage-sensitive sex reversal, adrenal hypoplasia congenital, critical region on the X chromosome, DAX-1 by qRT-PCR. Protein was quantified by Western analysis. Adrenal mRNA for CYP17, CYP11A1, and ACTH receptor was significantly reduced in LTH fetal sheep compared to controls. Similarly, CYP11A1 and CYP17 protein was reduced in the LTH group. CYP21, StAR, HSD3B2, SF-1 and DAX-1 expression was not altered in response to LTH. We conclude that expression of two key steroidogenic enzymes (CYP17, CYP11A1) regulating cortisol biosythesis and the ACTH receptor is lower in response to LTH. This likely represents an adaptive response to LTH preventing excessive cortisol production that would restrict fetal growth and potentially induce preterm delivery.
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C. A. Ducsay, K. Hyatt, M. Mlynarczyk, B. K. Root, K. M. Kaushal, and D. A. Myers Long-term hypoxia modulates expression of key genes regulating adrenomedullary function in the late gestation ovine fetus Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2007; 293(5): R1997 - R2005. [Abstract] [Full Text] [PDF]
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C. A. Ducsay, K. Hyatt, M. Mlynarczyk, K. M. Kaushal, and D. A. Myers Long-term hypoxia increases leptin receptors and plasma leptin concentrations in the late-gestation ovine fetus Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2006; 291(5): R1406 - R1413. [Abstract] [Full Text] [PDF]
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