Belo Najara O, Sairam M Ram, Dos Reis Adelina M
Department of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais, CEP 31270-901, Belo Horizonte, Minas Gerais, Brazil.
Endocrinology. 2008 Mar;149(3):1399-406. doi: 10.1210/en.2007-0572. Epub 2007 Dec 6.
Estrogen is considered a major regulator of adipose tissue in females. Estrogen increases circulating levels of atrial natriuretic peptide (ANP), a hormone with renal and cardiovascular effects. The aim of this study was to determine the status of the natriuretic peptide system in female follitropin-receptor knockout (FORKO) mice that could be associated with obesity and hypertension observed in these mutants. Furthermore, estradiol treatment was used to reverse alterations observed. FORKO and wild-type (WT) mice received daily injections of estradiol for 4 d. On the fifth day, blood was collected for determination of plasma ANP levels, and selected tissues were collected for determination of ANP, natriuretic peptide receptor type-A (NPR-A) and type-C (NPR-C) gene expression by RT-PCR and binding of [(125)I]ANP by autoradiography. At 5 months of age, FORKO mice were heavier and had more adipose tissue than WT mice. FORKO mice had lower plasma ANP levels and atrial ANP gene expression and higher renal and adipocyte NPR-C gene expression than WT mice. Estradiol treatment reduced weight gain and increased atrial ANP synthesis as well as decreased ANP clearance NPR-C receptors, resulting in elevation of circulating ANP level. In conclusion, this study shows that FORKO females have an impaired natriuretic peptide system, which may contribute to the susceptibility of FORKO mice to developing age-related hypertension previously shown in these animals. This study establishes a relation between estrogen, adipose tissue, and ANP, which may have important implications in menopausal women.
雌激素被认为是女性脂肪组织的主要调节因子。雌激素会增加心房利钠肽（ANP）的循环水平，ANP是一种对肾脏和心血管有影响的激素。本研究的目的是确定雌性促卵泡激素受体基因敲除（FORKO）小鼠中利钠肽系统的状态，该状态可能与这些突变体中观察到的肥胖和高血压有关。此外，使用雌二醇治疗来逆转观察到的改变。FORKO和野生型（WT）小鼠每天注射雌二醇，持续4天。在第5天，采集血液以测定血浆ANP水平，并采集选定的组织，通过逆转录聚合酶链反应（RT-PCR）测定ANP、A型利钠肽受体（NPR-A）和C型利钠肽受体（NPR-C）的基因表达，并通过放射自显影法测定[（125）I]ANP的结合情况。在5个月大时，FORKO小鼠比WT小鼠更重，且脂肪组织更多。与WT小鼠相比，FORKO小鼠的血浆ANP水平和心房ANP基因表达较低，而肾脏和脂肪细胞的NPR-C基因表达较高。雌二醇治疗减少了体重增加，增加了心房ANP的合成，并降低了ANP清除NPR-C受体，从而导致循环ANP水平升高。总之，本研究表明FORKO雌性小鼠的利钠肽系统受损，这可能是FORKO小鼠易患先前在这些动物中显示的与年龄相关高血压的原因。本研究建立了雌激素、脂肪组织和ANP之间的关系，这可能对绝经后女性具有重要意义。
