Kato J, Hirata S, Nozawa A, Mouri N
Department of Obstetrics and Gynecology, Yamanashi Medical University, Japan.
J Steroid Biochem Mol Biol. 1993 Dec;47(1-6):173-82. doi: 10.1016/0960-0760(93)90072-5.
The postnatal development of the progestin receptor (PR) system in the rat brain is a region-specific and stage-related process. In an attempt to analyze the molecular mechanism by which the dramatic change of gene expression of the PR occurs we have examined the level of PR mRNAs in the hypothalamus-preoptic area (HPOA) and cerebral cortex in development from fetal to postnatal stages of female rats. We used polymerase chain reaction to clone, from uterine cDNA, the cDNA corresponding to the steroid-binding domain of the PR forms 'A' and 'B' mRNA as well as the region around the translation-initiation site (ATG1) of the putative PR form 'B' mRNA. A quantitative reverse transcription-polymerase chain reaction assay was used to measure the level of mRNAs for PR forms 'A' and 'B' (total PR mRNAs) and PR form 'B'. There was a regional difference in the intracerebral distribution between the total and form 'B' mRNAs, indicating possible distinct mechanisms responsible for regulating the expression of the PR mRNAs. The PR mRNAs in the brain, already detectable 2 days before birth, increased at early neonatal stages. The total PR mRNAs in the cortex developed in a manner essentially similar to the PR protein at the early stages, but, surprisingly, unlike the receptor, the messages remained high at the later stages from day 18 to 8 weeks of life. On the other hand, the ontogeny of the cortical mRNA for form 'B', which predominantly existed in the region, resembled that of the cortical PR protein. In the HPOA the postnatal development of the form 'B' mRNAs was also roughly similar to the PR. These results suggest region-specific and stage-related gene expression of the PR isoform system in the developing brain: gene expression of form 'B' seems to be predominantly, first, "turned on" around birth, followed by form 'A' mRNA expression around days 8-12. Moreover, lowered levels of the cortical PR mRNAs in the propylthiouracil-induced hypothyroid rat, together with suppressed PR level, indicate a possible regulatory role of thyroid hormone on gene expression of the cortical receptor.
大鼠脑中孕激素受体（PR）系统的产后发育是一个区域特异性且与阶段相关的过程。为了分析PR基因表达发生显著变化的分子机制，我们检测了雌性大鼠从胎儿期到产后阶段下丘脑-视前区（HPOA）和大脑皮层中PR mRNA的水平。我们使用聚合酶链反应从子宫cDNA中克隆出与PR形式“A”和“B”mRNA的类固醇结合结构域相对应的cDNA，以及假定的PR形式“B”mRNA翻译起始位点（ATG1）周围的区域。采用定量逆转录-聚合酶链反应测定法来测量PR形式“A”和“B”（总PR mRNA）以及PR形式“B”的mRNA水平。总mRNA和形式“B”的mRNA在脑内分布存在区域差异，表明可能存在调节PR mRNA表达的不同机制。出生前2天即可检测到脑中的PR mRNA，在新生儿早期增加。皮层中的总PR mRNA在早期的发育方式与PR蛋白基本相似，但令人惊讶的是，与受体不同，在出生后第18天到8周的后期阶段，这些信息仍然很高。另一方面，主要存在于该区域的形式“B”的皮层mRNA的个体发生与皮层PR蛋白相似。在HPOA中，形式“B”mRNA的产后发育也与PR大致相似。这些结果表明发育中的大脑中PR异构体系统存在区域特异性和与阶段相关的基因表达：形式“B”的基因表达似乎首先在出生前后主要“开启”，随后在第8 - 12天左右出现形式“A”mRNA表达。此外，丙硫氧嘧啶诱导的甲状腺功能减退大鼠皮层PR mRNA水平降低，同时PR水平受到抑制，表明甲状腺激素可能对皮层受体的基因表达具有调节作用。
