Li Liu-An, Xia Dong, Wei Shi, Hartung J, Zhao Ru-Qian
Key Laboratory of Animal Physiology & Biochemistry, Nanjing Agricultural University, Nanjing, PR China.
Steroids. 2008 Sep;73(8):806-14. doi: 10.1016/j.steroids.2008.03.002. Epub 2008 Mar 18.
Our previous study demonstrated significant difference in the basal plasma cortisol levels between Erhualian (EHL) and Pietrain (PIE) pigs, implicating fundamental breed difference in adrenocortical function. The objectives of the present study were therefore to characterize the expression pattern of proteins involved in adrenal ACTH signaling and, including melanocortin type 2 receptor (MC2R), cAMP response element binding protein (CREB) and phosphorylated CREB (pCREB), steroidogenic acute regulatory protein (StAR), as well as that of the key enzymes involved in steroidogenesis in EHL and PIE pigs, in association with the plasma corticotrophin (ACTH) and cortisol levels. The plasma concentrations of the substrates for adrenal steroidogenesis, cholesterol and low-density lipoprotein (LDL) cholesterol, did not differ between breeds. Plasma concentration of ACTH and the adrenal contents of MC2R mRNA and protein were similar in two breeds of pigs, whereas the basal plasma concentrations of cortisol in EHL pigs were 1.5 folds higher than that in PIE pigs. The higher basal plasma cortisol levels in EHL pigs were found to be accompanied with the higher expression of ACTH post-receptor signaling components, cAMP, pCREB and StAR, as well as the higher expression of cholesterol side-chain cleavage cytochrome P450 (P450scc), 17alpha-hydroxylase cytochrome P450 (P450(17alpha)), 21-hydroxylase cytochrome P450 (P450c21) and 11beta-hydroxylase cytochrome P450 (P450(11beta)). These results indicated that the enhanced cAMP/PKA/pCREB-signaling system and augmented expression of StAR and steroidogenic enzymes are major attributes to the higher basal plasma cortisol concentrations in pigs.
我们之前的研究表明,二花脸猪(EHL)和皮特兰猪(PIE)的基础血浆皮质醇水平存在显著差异,这暗示了肾上腺皮质功能存在基本的品种差异。因此,本研究的目的是表征参与肾上腺促肾上腺皮质激素(ACTH)信号传导的蛋白质的表达模式,包括促黑素细胞激素2型受体(MC2R)、环磷酸腺苷反应元件结合蛋白(CREB)和磷酸化CREB(pCREB)、类固醇生成急性调节蛋白(StAR),以及EHL和PIE猪中参与类固醇生成的关键酶的表达模式,并与血浆促肾上腺皮质激素(ACTH)和皮质醇水平相关联。肾上腺类固醇生成底物胆固醇和低密度脂蛋白(LDL)胆固醇的血浆浓度在不同品种之间没有差异。两个猪品种的血浆ACTH浓度以及肾上腺中MC2R mRNA和蛋白质的含量相似,而EHL猪的基础血浆皮质醇浓度比PIE猪高1.5倍。结果发现,EHL猪较高的基础血浆皮质醇水平伴随着ACTH受体后信号传导成分、cAMP、pCREB和StAR的较高表达,以及胆固醇侧链裂解细胞色素P450(P450scc)、17α-羟化酶细胞色素P450(P450(17α))、21-羟化酶细胞色素P450(P450c21)和11β-羟化酶细胞色素P450(P450(11β))的较高表达。这些结果表明,增强的cAMP/PKA/pCREB信号系统以及StAR和类固醇生成酶表达的增加是猪基础血浆皮质醇浓度较高的主要原因。