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Proopiomelanocortin Processing in the Anterior Pituitary of the Ovine Fetus after Lesion of the Hypothalamic Paraventricular Nucleus

Department of Obstetrics and Gynecology (M.E.B., D.A.M.), University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104; and Department of Obstetrics and Gynecology (T.J.M.), University of Texas Health Sciences Center, San Antonio, Texas 78229

Address all correspondence and requests for reprints to: Dean A. Myers, Ph.D., Department of Obstetrics and Gynecology, College of Medicine, Suite 468, RP1, 800 North Research Parkway, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104. E-mail: dean-myers{at}ouhsc.edu.

The hypothalamic-pituitary-adrenocortical axis plays an essential role in the maturation of fetal organs and, in sheep, birth. Lesioning the paraventricular nucleus (PVN) in fetal sheep prevents adrenocortical maturation and parturition without altering plasma immunoreactive ACTH concentrations. The purpose of this study was to determine the effect of PVN lesion on anterior pituitary processing of proopiomelanocortin (POMC) to ACTH, plasma concentrations of ACTH and ACTH precursors (POMC; 22-kDa proACTH), and expression of subtilisin-like prohormone convertase 3 (SPC3) in corticotropes in fetal sheep. PVN lesion did not affect anterior pituitary POMC and 22-kDa proACTH levels, whereas ACTH was significantly affected. The ACTH precursor (POMC plus 22-kDa proACTH) to ACTH ratio in the anterior pituitary was significantly increased after PVN lesion. Post-PVN lesion, fetal plasma ACTH_1–39, was below the limit of detection, whereas ACTH precursors (POMC plus 22-kDa proACTH) were not affected. In the inferior region of the anterior pituitary, 40–50% of corticotropes had detectable SPC3 hybridization signal, and PVN lesion did not change the extent of colocalization of POMC and SPC3, or SPC3 mRNA levels within corticotropes. Neither the percent of corticotropes in the superior region containing SPC3 hybridization (7–12%) or hybridization signal strength was altered in response to PVN lesion. In conclusion, the fetal PVN is necessary for sustaining adequate anterior pituitary processing of POMC to ACTH and ACTH release needed for maturing the adrenal cortex in the sheep fetus.

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				D. A. Myers, K. Hyatt, M. Mlynarczyk, I. M. Bird, and C. A. Ducsay Long-term hypoxia represses the expression of key genes regulating cortisol biosynthesis in the near-term ovine fetus Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2005; 289(6): R1707 - R1714. [Abstract] [Full Text] [PDF]