Hormonal regulation of androgen receptor messenger RNA in the medial preoptic area of the male rat
Hormonal regulation of androgen receptor messenger RNA in the medial preoptic area of the male rat
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DOI：
10.1016/0169-328x(95)00353-t
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发表时间：
1996-07-01
期刊：
影响因子：
--
通讯作者：
Hejna, G
中科院分区：
文献类型：
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作者：
Handa, RJ;Kerr, JE;Hejna, G
在成年雄性大鼠中，雄激素和雌激素在调节雄性生殖行为方面具有协同作用。为了探讨这种协同作用的一些分子机制，我们研究了雄激素受体(AR)和雌激素受体(ER)mRNAs在成年雄性大鼠视前内侧区(MPOA)和终纹床核(BST)的分布和激素调节。通过原位杂交，发现AR和ER的mRNAs以重叠但独特的模式分布。AR基因在内侧视前核的中央部和BST的主核的密度最高。成年雄性大鼠去性腺(GDX)后4天左右脑区杂交密度增加，2个月后下降。相反，GDX后ER基因表达增加，且无论作用时间长短，ER基因表达均保持在较高水平。用双氢睾酮(DHT)处理成年雄性GDX，可逆转GDX对去势大鼠短期和长期AR基因表达的影响，但对MPOA和BST的ER基因表达无影响。雌激素处理只增加长期去势大鼠的AR mRNA，而降低长期和短期去势大鼠的ER mRNA。免疫细胞化学检测显示，AR的分布与AR mRNA的分布相似；然而，短期和长期GDX后，AR免疫反应在MPOA和BST中都降低了。在体外，[H-3]DHT结合在视前区的胞浆中表现出明显的结合，但GDX作用时间的长短对结合没有影响。这些数据表明，AR mRNA的调节模式是该受体所特有的，并不遵循ER mRNA的调节模式。此外，尽管AR mRNA和AR蛋白在MPOA内的分布是一致的，但由于去势或激素处理而导致的mRNA水平的变化并不会导致相应的结合变化。这种mRNA和结合之间的不匹配表明了AR的复杂调控，而不仅仅是转录上的变化。
In the adult male rat, androgen and estrogen synergize in the regulation of male reproductive behaviors. To explore some of the molecular mechanisms underlying this synergism we examined the distribution and hormonal regulation of androgen receptor (AR) and estrogen receptor (ER) mRNAs in the medial preoptic area (MPOA) and bed nucleus of the stria terminalis (BST) of the adult male rat. Using in situ hybridization, AR and ER mRNAs were found to be distributed in overlapping but unique patterns. The highest density of AR mRNA was found in the central part of the medial preoptic n, and the principal n. of the BST. Gonadectomy (GDX) of adult male rats caused an increase in hybridization density in both brain areas after 4 days followed by a decrease after 2 months. in contrast, ER mRNA was increased following GDX and remained high regardless of length of time. Treatment of adult GDX'd males with dihydrotestosterone (DHT) reversed the effects of GDX on AR mRNA at both the short and long-term castrate bur had no effect on ER mRNA in both the MPOA and BST. Estrogen treatment increased AR mRNA in the long-term castrate only and decreased ER mRNA in both long- and short-term castrates. Immunocytochemical detection of AR revealed a similar distribution to AR mRNA; however, AR immunoreactivity was reduced in the MPOA and BST after both short- and long-term GDX. In vitro [H-3]DHT binding in cytosols of the preoptic area showed appreciable binding but there was no effect of length of time following GDX. These data show that the pattern of regulation of AR mRNA is unique to this receptor type and does not follow the pattern of regulation of the ER mRNA. Furthermore, although the distribution of AR mRNA and AR protein coincide within the MPOA, changes in mRNA levels as a result of castration or hormone treatment do not result in corresponding changes in binding. This mismatch between mRNA and binding suggests a complex regulation of AR beyond simply changes in transcription.