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The aim of this study was to determine the ontogenetic profiles

The aim of this study was to determine the ontogenetic profiles in remaining and right ventricle of genes implicated in cardiac growth, including mineralocorticoid (MR) and glucocorticoid (GR) receptor, 11 beta-hydroxysteroid dehydrogenase (11-HSD) 1 and 2 and genes of the angiotensin system and insulin-like growth factor (IGF) family. not decrease, but both 11-HSD 1 and 2 mRNA levels improved after birth. ACE1 expression in LV and RV sharply raises just before parturition, whereas ACE2 decreased in the LV and RV in late gestation. IGF2, IGF2R, and IGFBP2 expression levels substantially decreased in late gestation in LV and RV; IGF2R also decreased with age in LV. These patterns suggest that reduced expression of genes related to IGF and angiotensin II action happen as proliferative activity declines and terminal differentiation happens in the late gestation fetal center. 0.05) a: 80d, b: 100d, c:120d, d: 130d, f: 145d, g: newborn. Table 1 Results of buy Salinomycin linear regression analysis of mRNA expression vs age 0.05 (= 32 for LV, = 20 for RV). +shows positive relation between gene expression and age (slope of relation between age and Ct was negative) ?indicates negative relation between gene expression and age (slope of relation between age and Ct was positive. Table 2 Expression ratio of -HSD1 to 11-HSD2, IGF2 to IGF1, AT1R to AT2R, and ACE1 to ACE2 in LV and RV mRNA 0.05) a: vs 80d, b: vs 100d, c: vs120d, d: vs 130d, f: vs 145d, g: vs postnatal lambs; nm, not measured. Fetal secretion of cortisol increases exponentially before birth in humans and in sheep (Liggins, 1974). Previous studies have suggested that even small increases in fetal cortisol can alter heart mass (Jensen et al., 2005; Jensen et al., 2002), suggesting an action of cortisol at MR and/or GR in fetal myocytes. The ability of cortisol to bind at MR and/or GR, however, depends in large part on the activity of 11-HSD1 relative to that of the cortisol inactivating enzyme 11-HSD2 (Mihailidou and Funder, 2005; Seckl and Walker, 2001). The maintenance of high 11-HSD1 expression relative to 11-HSD2 within both ventricles of the heart throughout all of late gestation indicates a potential role of cortisol within the heart in the late gestation fetus. However the decrease in MR and GR expression in LV with advancing age suggests that as plasma cortisol concentrations are increasing in vivo, proliferative effects of cortisol CGB in LV may be reduced. 1.2. Genes relating to the IGF system There was an effect of age on expression of IGF2, IGF1R, IGF2R, and IGFBP-2 mRNAs in the LV and on IGF2, IGF2R, and IGFBP2 mRNAs in the RV (Fig. 2). Expression of all of these genes was significantly decreased with advancing age, reaching low levels of expression near birth (Table 1). In contrast, IGF1 did not change in either RV or LV, and IGF1R did not change with age in RV. The observed decrease in expression of IGF2 in both LV and RV agrees with previous observations by others (Cheung et al., 1996; Delhanty and Han, 1993). However in these studies, investigators also found decreased expression of IGF1 in the left ventricle from 100d gestation toward term, whereas the decrease we observed after 80d was not significant. Open in a separate window Fig. 2 Expression of mRNA for IGF1, IGF2, IGF1R, IGF2R and IGFBP2 from left and right ventricles of fetal and newborn lambs. IGFBP3 were measured in left ventricle only. Ages and significance are buy Salinomycin as indicated in legend to (Fig. 1). The pattern of decreased IGF1R in LV parallels the buy Salinomycin reduced number of LV myocytes entering the cell cycle in late gestation after 120 days, whereas the decrease in IGF2 parallels the reduction in mononuclear myocytes in both ventricles (Jonker et al., 2007). IGF2 and IGF1 both appear to stimulate myocyte proliferation in vitro. IGF2 stimulated an increase in proliferation of myocytes in cultures of prenatal, but not neonatal, rat myocytes (Liu et al., 1996). In vivo.