Sex difference in hepatic peroxisome proliferator-activated receptor α expression:: Influence of pituitary and gonadal hormones

Sex difference in hepatic peroxisome proliferator-activated receptor α expression:: Influence of pituitary and gonadal hormones
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DOI:
10.1210/en.2002-220630
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发表时间:
2003-01-01
期刊:
影响因子:
4.8
通讯作者:
Oscarsson, J
Oscarsson, J
中科院分区:
医学2区
文献类型:
--
作者:
Jalouli, M;Carlsson, L;Oscarsson, J

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过氧化物酶体增殖物激活受体(过氧化物酶体增殖物激活受体)α是一种核受体,主要在脂肪酸氧化程度高的组织中表达,如肝脏、心脏和骨骼肌。不饱和脂肪酸及其衍生物和贝特类可激活PPARalpha。雄性大鼠比雌性大鼠对贝特类药物更敏感。因此,我们想研究PPARalpha表达是否存在性别差异。雄性大鼠肝组织中PPARalpha mRNA和蛋白水平高于雌性大鼠。两种性别动物中,禁食使肝脏PPARalpha mRNA水平升高至相似程度。雄性大鼠的性腺切除术降低了PPAR α mRNA的表达水平,与完整和性腺切除的雌性大鼠相似。垂体切除增加肝脏PPARalpha mRNA和蛋白水平。垂体切除术后PPARalpha mRNA的增加在女性中比在男性中更明显。GH处理降低了PPARalpha mRNA和蛋白水平,但GH的性别分化分泌模式并不决定PPARalpha的性别分化表达。PPARamRNA在心脏或比目鱼肌中的表达不受性别、性腺切除、垂体切除或GH处理的影响。总之,垂体依赖性激素特异性调节肝脏PPARalpha表达。性激素调节肝脏PPARalpha水平的性别差异,但不是通过性二型GH分泌模式。
Peroxisome proliferator-activated receptor (PPAR) alpha is a nuclear receptor that is mainly expressed in tissues with a high degree of fatty acid oxidation such as liver, heart, and skeletal muscle. Unsaturated fatty acids, their derivatives, and fibrates activate PPARalpha. Male rats are more responsive to fibrates than female rats. We therefore wanted to investigate if there is a sex difference in PPARalpha expression. Male rats had higher levels of hepatic PPARalpha mRNA and protein than female rats. Fasting increased hepatic PPARalpha mRNA levels to a similar degree in both sexes. Gonadectomy of male rats decreased PPARalpha mRNA expression to similar levels as in intact and gonadectomized female rats. Hypophysectomy increased hepatic PPARalpha mRNA and protein levels. The increase in PPARalpha mRNA after hypophysectomy was more pronounced in females than in males. GH treatment decreased PPARalpha mRNA and protein levels, but the sex-differentiated secretory pattern of GH does not determine the sex-differentiated expression of PPARalpha. The expression of PPARa mRNA in heart or soleus muscle was not influenced by gender, gonadectomy, hypophysectomy, or GH treatment. In summary, pituitary-dependent hormones specifically regulate hepatic PPARalpha expression. Sex hormones regulate the sex difference in hepatic PPARalpha levels, but not via the sexually dimorphic GH secretory pattern.