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Title:   Author  item
                                            KLEMCKE, HAROLD - FORMER ARS EMPLOYEEitem
                                            SAMPATH-KUMAR, R - UNIV WESTERN ONTARIOitem
                                            YANG, K - UNIV WESTERN ONTARIOitem
                                            Vallet, Jeffitem
                                            Christenson, Ronald
  Submitted to: Biology of Reproduction
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 8/6/2003
                                    Publication  Date: 12/20/2003
                                    Citation: Klemcke, H.G., Sampath-Kumar, R., Yang, K., Vallet, J.L., Christenson, R.K. 2003. 11beta-Hydroxysteroid dehydrogenase and glucocorticoid receptor messenger RNA expression in porcine placentae: effects of stage of gestation, breed, and uterine environment. Biology of Reproduction. 69(6):1945-1950.Interpretive Summary: There are 30-50% fetal losses in pigs, and when the uterus is crowded, additional losses occur between days 25 and 40 of gestation. Such occult fetal mortality greatly reduces swine litter size, and imposes economic losses on swine producers.  In order to increase swine litter size it is important to understand factors that limit litter size, and to understand those factors that are important for normal prenatal development. One such factor could be the steroid hormone cortisol.  In other species optimal cortisol concentrations are beneficial to normal development, yet excessive concentrations are known to limit growth and increase mortality.  There are a number of factors that regulate the biological effects of cortisol:  the enzyme 11beta-hydroxysteroid dehydrogenase Type 1 (11betaHSD-1) which converts inactive cortisone into active cortisol; the enzyme 11beta-hydroxysteroid dehydrogenase Type 2 (11betaHSD-2) which inactivates cortisol by converting it to cortisone; and glucocorticoid receptors (GR) which permit the steroid to activate specific target cells. The current study was conducted to determine if these three regulators were present in pig placentae at early stages of gestation; to determine if they varied with uterine environment and pig breed; and to determine if they were associated with changes in fetal mortality. This study is the first to demonstrate the presence of these three factors in pig placentae at these early gestational stages (days 24-40 of pregnancy).  The data further indicate that the enzyme 11betaHSD-2 is altered by uterine environment and pig breed.  The nature of these changes may suggest a role for this enzyme in maintaining a uterine environment via effects on cortisol that is optimal for fetal survival.
                                Technical Abstract: Glucocorticoids are known to influence many aspects of prenatal development. Three important regulators of glucocorticoid actions at the cellular level are the enzymes 11beta-hydroxysteroid dehydrogenase Type 1 (11betaHSD-1), 11beta-hydroxysteroid dehydrogenase Type 2 (11betaHSD-2), and glucocorticoid receptors (GR). A study was conducted to determine the presence of these regulators of glucocorticoid action in porcine placentae during early gestation (days 24-40; term = 114 days) and to examine the influence of breed and uterine environment. Three pig models differing in uterine environment as reflected by embryonic survival from days 24-40 were used: intact white crossbred gilts (WC-INT); white crossbred gilts that had been unilaterally hysterectomized- ovariectomized before puberty (WC-UHO); and prolific, intact Meishan gilts (ME). Porcine specific partial cDNAs for 11betaHSD-1 and 11betaHSD-2 and a cRNA for Gralpha were developed and used to produce **32P-labeled probes for Northern analyses. 11betaHSD dehydrogenase activity was measured in vitro at saturating concentrations of substrate and coenzyme. At day 24 of gestation 11betaHSD-2 mRNA, dehydrogenase activity, and GR mRNA expression were present, but 11betaHSD-1 mRNA expression was absent. All three mRNAs and dehydrogenase activity increased (P < 0.01) by day 40. On day 30 placental 11betaHSD-2 mRNA expression was decreased (P = 0.03) 47% in WC-UHO vs WC-INT. Placental 11beta-HSD dehydrogenase activity was twofold greater (P < 0.01) in ME vs WC-INT on day 24 of gestation. These results demonstrate for the first time the presence of 11betaHSD-1, 11betaHSD-2, and GR mRNA as well as 11beta-HSD dehydrogenase activity in the porcine placenta during early pregnancy. Moreover, the present study indicates the existence of some breed and uterine environmental differences for placental 11betaHSD-2 mRNA and associated dehydrogenase activity, suggesting a role for glucocorticoids in optimal early porcine embryonic development and survival.


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