Raso Giuseppina Mattace, Bianco Giuseppe, Iacono Anna, Esposito Emanuela, Autore Giuseppina, Ferrante Maria Carmela, Calignano Antonio, Meli Rosaria
Department of Experimental Pharmacology, University of Naples, Federico II, via D. Montesano, 49-80131 Naples, Italy.
J Endocrinol. 2007 Sep;194(3):611-9. doi: 10.1677/JOE-07-0159.
Leptin and/or ghrelin, initially thought to be considered messengers of energy metabolism, are now considered to play a role in normal and complicated pregnancy. In this study, pregnant, spontaneously hypertensive rats (SHR) have been used to evaluate, for the first time, the modification of leptin and ghrelin both at serum and tissue levels. In SHR, we evaluate plasma leptin level and tissue protein expression in both placenta and adipose tissue at the end of gestation (day 20) versus normotensive Wistar-Kyoto (WKY) animals. The expression of functional leptin receptor (Ob-Rb) in peripheral tissues and in the hypothalamus was evaluated. Moreover, we measured plasma ghrelin level and its mRNA expression in the stomach and placenta. SHR strain presented significantly lower plasma leptin levels when compared with those found in pregnant or not WKY controls. Interestingly, in the placenta, leptin gene expression was higher in SHR than normotensive WKY. Moreover, we demonstrated a resistance to the effects of leptin via 'downregulation' of hypothalamic receptors in pregnant SHR. Conversely, SHR presented significantly higher ghrelin plasma levels when compared with those found in pregnant or not WKY. However, we observed that ghrelin level in the stomach of SHR did not change during pregnancy, and on the opposite, mRNA ghrelin in the placenta of SHR was lower than that of normotensive rats, suggesting a different production of this hormone in the fetal-placental unit. These data gain further insight into metabolic hormone modifications observed in a model of pre-existing hypertension associated with pregnancy.
瘦素和/或胃饥饿素最初被认为是能量代谢的信使,现在则被认为在正常和复杂的妊娠过程中发挥作用。在本研究中,首次使用妊娠自发性高血压大鼠(SHR)来评估血清和组织水平上瘦素和胃饥饿素的变化。在SHR中,我们评估了妊娠末期(第20天)与正常血压的Wistar-Kyoto(WKY)动物相比,胎盘和脂肪组织中的血浆瘦素水平和组织蛋白表达。评估了外周组织和下丘脑中功能性瘦素受体(Ob-Rb)的表达。此外,我们测量了胃和胎盘中的血浆胃饥饿素水平及其mRNA表达。与妊娠或未妊娠的WKY对照组相比,SHR品系的血浆瘦素水平显著降低。有趣的是,在胎盘中,SHR的瘦素基因表达高于正常血压的WKY。此外,我们证明妊娠SHR通过下丘脑受体的“下调”对瘦素的作用产生抵抗。相反,与妊娠或未妊娠的WKY相比,SHR的血浆胃饥饿素水平显著升高。然而,我们观察到SHR胃中的胃饥饿素水平在妊娠期间没有变化,相反,SHR胎盘的胃饥饿素mRNA低于正常血压大鼠,这表明胎儿-胎盘单位中这种激素的产生不同。这些数据进一步深入了解了在与妊娠相关的原发性高血压模型中观察到的代谢激素变化。