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DEVELOPMENTAL PHYSIOLOGY AND PREGNANCY

Long-term hypoxia enhances proopiomelanocortin processing in the near-term ovine fetus

¹Department of Obstetrics and Gynecology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma; and ²Center for Perinatal Biology, Loma Linda University School of Medicine, Loma Linda, California

Submitted 12 October 2004 ; accepted in final form 19 December 2004

Secondary stressors in long-term hypoxic (LTH) fetal sheep lead to altered function of the hypothalamic-pituitary-adrenal axis. Although ACTH is considered the primary mediator of glucocorticoid production in fetal sheep, proopiomelanocortin (POMC) and 22-kDa pro-ACTH (22-kDa ACTH) have been implicated in the regulation of cortisol production in the ovine fetus. This study was designed to determine whether POMC expression and processing are altered after 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 days 139–141, fetal anterior pituitaries were collected from normoxic control and LTH fetuses. We measured POMC and corticotrophin-releasing factor type 1 receptor (CRF₁-R) mRNA using quantitative real-time PCR, and we used Western blot analysis for quantitation of ACTH, ACTH precursor, and CRF₁-R proteins. We measured plasma ACTH_1–39 using a two-site immunoradiometric assay specific for ACTH_1–39. Plasma ACTH precursors were measured by ELISA. Anterior pituitary POMC mRNA levels were not different between groups, whereas CRF₁-R levels were significantly higher in the LTH anterior pituitaries compared with control (P < 0.05). In contrast, protein levels of POMC, CRF₁-R, 22-kDa ACTH, and ACTH_1–39 were significantly lower in the LTH group. Plasma concentrations of both ACTH precursors and ACTH_1–39 were significantly elevated in LTH fetuses, whereas the ratio of plasma precursors to ACTH was significantly lower. We conclude that LTH results in enhanced POMC processing and/or release to ACTH and increased hypothalamic drive.

ACTH; adrenocorticotropin; anterior pituitary; sheep

This article has been cited by other articles:

				B. Root, J. Abrassart, D. A. Myers, T. Monau, and C. A. Ducsay Expression and Distribution of Glucocorticoid Receptors in the Ovine Fetal Adrenal Cortex: Effect of Long-term Hypoxia Reproductive Sciences, May 1, 2008; 15(5): 517 - 528. [Abstract] [PDF]

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