Development of prostaglandin endoperoxide synthase expression in the ovine fetal central nervous system and pituitary

Abstract

In this study, we tested the hypothesis that prostaglandin endoperoxide synthase -1 and -2 (PGHS-1 and PGHS-2) are expressed throughout the latter half of gestation in ovine fetal brain and pituitary. Hypothalamus, pituitary, hippocampus, brainstem, cortex and cerebellum were collected from fetal sheep at 80, 100, 120, 130, 145 days of gestational age (DGA), 1 and 7 days postpartum lambs, and from adult ewes (n=4-5 per group). mRNA and protein were isolated from each region, and expression of Prostaglandin Synthase -1 (PGHS-1) and -2 (PGHS-2) were evaluated using real-time RT-PCR and western blot. PGHS-1 and -2 were detected in every brain region at every age tested. Both enzymes were measured in highest abundance in hippocampus and cerebral cortex, and lowest in brainstem and pituitary. PGHS-1 and -2 mRNA's were upregulated in hypothalamus and pituitary after 100 DGA. The hippocampus exhibited decreases in PGHS-1 and increases in PGHS-2 mRNA after 80 DGA. Brainstem PGHS-1 and -2 and cortex PGHS-2 exhibited robust increases in mRNA postpartum, while cerebellar PGHS-1 and -2 mRNA's were upregulated at 120 DGA. Tissue concentrations of PGE 2 correlated with PGHS-2 mRNA, but not to other variables. We conclude that the regulation of expression of these enzymes is region-specific, suggesting that the activity of these enzymes is likely to be critical for brain development in the late-gestation ovine fetus. Keywords parturition; prostanoid; neuroendocrinology; fetus; HPA axis; brain RESULTS AND DISCUSSIONProstaglandins are involved in many physiological processes such as inflammation, response to pain, and vascular regulation (Morita, 2002;Smith et al., 2000). Generated within the fetal central nervous system, prostanoids modulate both basal-and stress-induced secretion of adrenocorticotropin (Reimsnider and Wood, 2005;Reimsnider and Wood, 2006;, modulate blood pressure regulatory systems (Reimsnider and Wood, 2006) and influence fetal breathing movements (Adamson et al., 1997). Both PGHS-1 and -2 are expressed in the fetal brain (Tong et al., 2002;Deauseault et al., 2000;Norton et al., 1996), and there is evidence that prostanoids are synthesized within the fetal central nervous system Address all correspondence to: Charles E. Wood, Ph.D., Department of Physiology and Functional Genomics, PO Box 100274, University of Florida College of Medicine, Gainesville, FL 32610-0274, (352)-392-4488 voice, (352)-392-8340 fax, woodc@ufl.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptGene Expr Patterns. Author manuscript; available in PMC 20...

Interaction of PGHS-2 and glutamatergic mechanisms controlling the ovine fetal hypothalamus-pituitary-adrenal axis

“…What is unclear is where this interaction occurs. PGHS-2 abundance is highest in the cerebral cortex and hippocampus, with lower expression in the hypothalamus and brain stem (8). This pattern of expression in the fetal sheep is similar to that in the adult rat (8,13).…”

“…PGHS-2 abundance is highest in the cerebral cortex and hippocampus, with lower expression in the hypothalamus and brain stem (8). This pattern of expression in the fetal sheep is similar to that in the adult rat (8,13). The infusion of nimesulide reduces prostaglandin generation throughout the brain (7), and general levels of expression of PGHS-2 do not provide useful clues as to which regions are important with regard to NMDA-PGHS-2 interactions in control of the fetal HPA axis.…”

Complex Actions of Estradiol-3-Sulfate in Late Gestation Fetal Brain

“…Pituitary was not used in the present study. Gene expression studies for estrogen receptor and prostaglandin synthase isoforms and for components of the fetal hypothalamus-pituitary-adrenal axis have been previously performed on these tissues and previously reported 4, 17, 18 .…”

Chemoreflex Activity Increases Prostaglandin Endoperoxide Synthase mRNA Expression in the Late-Gestation Fetal Sheep Brain

“…Interestingly, the negative effect of ketamine and denervation was apparent in hippocampus. We have consistently found that the level of expression of PGHS in late gestation fetal sheep is highest in hippocampus and cerebral cortex 33 ; perhaps it should not be surprising that a manipulation that reduces expression would be best observed in structures with the highest expression levels.…”