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半综合分析雄性大鼠海马体中与出生后年龄相关的性激素合成酶和性激素受体的 mRNA 表达变化。

Semicomprehensive analysis of the postnatal age-related changes in the mRNA expression of sex steroidogenic enzymes and sex steroid receptors in the male rat hippocampus.

机构信息

Department of Biophysics and Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, Tokyo 153-8902, Japan.

出版信息

Endocrinology. 2010 Dec;151(12):5795-806. doi: 10.1210/en.2010-0581. Epub 2010 Nov 3.

Abstract

Although sex steroids play a crucial role in the postnatal brain development, the age-related changes in the hippocampal steroidogenesis remain largely unknown. We performed comprehensive investigations for the mRNA expressions of 26 sex steroidogenic enzymes/proteins and three sex steroid receptors in the male rat hippocampus, at the ages of postnatal day (PD) 1, PD4, PD7, PD10, PD14, 4 wk, and 12 wk (adult), by RT-PCR/Southern blotting analysis. The relative expression levels of these enzymes/receptors at PD1 were Srd5a1 > Star > Ar ∼ Hsd17b4 ∼ Hsd17b1 ∼ Hsd17b7 ∼ Esr1 ∼ Srd5a2 > Hsd17b3 > Esr2 > Cyp11a1 > Cyp17a1 > Cyp19a1 ∼ Hsd17b2 > 3β-hydroxysteroid dehydrogenase I. The mRNA levels of essential enzymes for progesterone/testosterone/estradiol metabolisms (Cyp17a1, Hsd17b7, and Cyp19a1) were approximately constant between PD1 and PD14 and then declined toward the adult levels. Cyp11a1 increased during PD4-PD14 and then considerably decreased toward the adult level (∼8% of PD1). Hsd17b1, Hsd17b2, and 3β-hydroxysteroid dehydrogenase I mRNA decreased approximately monotonously. Hsd17b3 increased to approximately 200% of PD1 during PD4-PD14 and was maintained at this high level. The 5α-reductase mRNA was maintained constant (Srd5a1) or decreased monotonically (Srd5a2) toward the adult level. The Esr1 level peaked at PD4 and decreased toward the adult level, whereas Ar greatly increased during PD1-PD14 and was maintained at this high level. The Star and Hsd17b4 levels were maintained constant from neonate to adult. These results suggest that the hippocampal sex steroidogenic properties are substantially altered during the postnatal development processes, which might contribute to brain sexual maturation.

摘要

虽然性激素在产后大脑发育中起着至关重要的作用,但海马类固醇生成的年龄相关变化在很大程度上仍不清楚。我们通过 RT-PCR/Southern 印迹分析,研究了雄性大鼠海马体中 26 种性激素合成酶/蛋白和 3 种性激素受体的 mRNA 表达,分别在出生后第 1 天(PD1)、第 4 天(PD4)、第 7 天(PD7)、第 10 天(PD10)、第 14 天(PD14)、4 周龄和 12 周龄(成年)时进行了研究。在 PD1 时,这些酶/受体的相对表达水平为 Srd5a1>Star>Ar∼Hsd17b4∼Hsd17b1∼Hsd17b7∼Esr1∼Srd5a2>Hsd17b3>Esr2>Cyp11a1>Cyp17a1>Cyp19a1∼Hsd17b2>3β-羟甾脱氢酶 I。孕酮/睾酮/雌二醇代谢的必需酶(Cyp17a1、Hsd17b7 和 Cyp19a1)的 mRNA 水平在 PD1 至 PD14 之间基本保持不变,然后下降到成年水平。Cyp11a1 在 PD4-PD14 期间增加,然后急剧下降到成年水平(PD1 的约 8%)。Hsd17b1、Hsd17b2 和 3β-羟甾脱氢酶 I 的 mRNA 大致单调下降。Hsd17b3 在 PD4-PD14 期间增加到 PD1 的约 200%,并保持在这个高水平。5α-还原酶的 mRNA 水平保持恒定(Srd5a1)或单调下降(Srd5a2)到成年水平。Esr1 水平在 PD4 时达到峰值,然后下降到成年水平,而 Ar 在 PD1-PD14 期间大大增加,并保持在这个高水平。Star 和 Hsd17b4 的水平从新生儿到成年保持不变。这些结果表明,海马体的性激素生成特性在出生后发育过程中发生了实质性的改变,这可能有助于大脑的性成熟。

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