Molecular aspects of brain aromatase cytochrome P450

Molecular aspects of brain aromatase cytochrome P450
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脑芳香酶细胞色素 P450 的分子方面

DOI:
10.1016/s0960-0760(97)80035-0
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发表时间:
1997
期刊:
The Journal of Steroid Biochemistry and Molecular Biology
影响因子:
--
通讯作者:
E. Lephart
E. Lephart
中科院分区:
--
文献类型:
--
作者:
E. Lephart

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芳香酶细胞色素 P450 (P450arom) 酶活性催化特定大脑区域中雄激素转化为雌激素。在中枢神经系统(CNS)发育过程中,局部雌激素的形成影响神经结构的性别分化,调节神经内分泌功能和性行为。提出了啮齿动物大脑性别分化的拟议机制(和重新检查)。 P450arom 雄激素代谢的代谢途径在雄性大鼠不同产前和产后发育间隔的内侧基底下丘脑 (MBH) 组织中进行了表征。使用饱和浓度的[3H]睾酮作为底物测定P450arom酶活性,并通过闪烁计数对速率进行定量。 MBH P450arom 活性在产前发育期间最高(即 3-6 pmol/h/mg 蛋白质),在新生儿和幼年动物中下降至中等水平(约 1 pmol/h/mg 蛋白质),然后在成年动物中继续下降至低活性率(约 80 fmol/h/mg 蛋白质)。 P450arom 基因的调节以一系列分子生物学研究为特征,其中大脑 P450arom 的控制机制是在 MBH 和杏仁体组织部位确定的。提供了围产期大鼠大脑 P450arom 特异性 mRNA 的证据,以及与大鼠卵巢、大鼠 Leydig 肿瘤细胞系 (R2C) 和人胎儿脑 P450arom 的比较。具体而言,与大鼠卵巢组织或R2C细胞系相比,围产期大鼠脑组织中的P450arom基因表达是由不同的启动子驱动的,而人胎儿脑组织利用与啮齿动物中观察到的几乎相同的启动子片段。这些发现提供了对大脑 P450arom 基因表达调节的深入了解,并表明在围产期发育过程中对该基因的表达存在额外的控制水平。然而,需要进一步研究来了解大脑 P450arom 表达的这种复杂发育模式的分子基础。
Aromatase cytochrome P450 (P450arom) enzyme activity catalyses the conversion of androgens to estrogens in specific brain areas. During central nervous system (CNS) development local estrogen formation influences sexual differentiation of neural structures, regulates neuroendocrine functions and sexual behavior. A proposed mechanism (and re-examination) of the sexual differentiation of the rodent brain is presented. The metabolic pathway of androgen metabolism by P450arom was characterized in the medial basal hypothalamic (MBH) tissue from male rats during various prenatal and postnatal developmental intervals. The P450arom enzyme activity was determined using a saturating concentration of [3H]testosterone as the substrate, and the rates were quantified by scintillation counting. The MBH P450arom activity was highest during prenatal development (i.e. 3–6 pmol/h/mg protein), declined to moderate levels in newborns and infantile animals (approximately 1 pmol/h/mg protein) and then continued to decline to low activity rates in adult animals (approximately 80 fmol/h/mg protein). Regulation of the P450arom gene was characterized by a series of molecular biology studies where the controlling mechanism for brain P450arom was determined in MBH and amygdaloid tissue sites. Evidence for brain P450arom-specific mRNA in perinatal rats is presented as well as comparisons with rat ovary, a rat Leydig tumor cell line (R2C) and human fetal brain P450arom. Specifically, P450arom gene expression is driven in perinatal rat brain tissue by a different promoter compared to rat ovarian tissue or a R2C cell line, whereas human fetal brain tissue utilizes an almost identical promoter segment to that observed in the rodent. These findings provide an insight into the regulation of brain P450arom gene expression and suggest that there is an additional level of control for the expression of this gene during perinatal development. However, further study is necessary to understand the molecular basis of this complex developmental pattern of brain P450arom expression.
DOI: 10.1210/mend.7.6.8395654
发表时间: 1993-06
影响因子: --
作者:
J. Lynch;D. Lala;J. Peluso;W. Luo;K. Parker;B. White
通讯作者: J. Lynch;D. Lala;J. Peluso;W. Luo;K. Parker;B. White
编码鸡细胞色素 P-450arom(芳香酶)的功能性 cDNA 的表达,催化雄激素形成雌激素。
DOI: --
发表时间: 1988
期刊: The Journal of biological chemistry
影响因子: --
作者:
McPhaul,MJ;Noble,JF;Simpson,ER;Mendelson,CR;Wilson,JD
通讯作者: Wilson,JD
编码牛芳香酶细胞色素 P450 的互补脱氧核糖核酸插入片段的分离和表征。
DOI: 10.1210/endo.133.5.8404644
发表时间: 1993
期刊: Endocrinology
影响因子: 4.8
作者:
Hinshelwood,MM;Corbin,CJ;Tsang,PC;Simpson,ER
通讯作者: Simpson,ER
DOI: 10.1210/edrv-15-3-342
发表时间: 1994-06
期刊: Endocrine reviews
影响因子: 20.3
作者:
E. Simpson;M. Mahendroo;G. Means;M. Kilgore;M. Hinshelwood;S. Graham-Lorence;B. Amarneh;Yuji Ito
通讯作者: E. Simpson;M. Mahendroo;G. Means;M. Kilgore;M. Hinshelwood;S. Graham-Lorence;B. Amarneh;Yuji Ito