Response of tyrosine hydroxylase and GTP cyclohydrolase I gene expression to estrogen in brain catecholaminergic regions varies with mode of administration.
Response of tyrosine hydroxylase and GTP cyclohydrolase I gene expression to estrogen in brain catecholaminergic regions varies with mode of administration.
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大脑儿茶酚胺能区域酪氨酸羟化酶和 GTP 环化水解酶 I 基因表达对雌激素的反应随给药方式的不同而变化。
DOI：
10.1016/j.brainres.2004.04.002
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Sabban,EstherL
中科院分区：
文献类型：
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作者：
Serova,LidiaI;Maharjan,Shreekrishna;Huang,An;Sun,Dong;Kaley,Gabor;Sabban,EstherL
本实验观察了不同剂量、不同给药方式和不同给药时间的雌二醇对去卵巢雌性大鼠脑内不同部位儿茶酚胺能神经元的影响。我们确定了酪氨酸羟化酶（TH）的mRNA水平的变化，在儿茶酚胺（CA）的GTP环化水解酶I（GTPCH）的生物合成的限速酶，以及四氢生物蝶呤（BH 4）的生物合成的限速酶，和BH 4的浓度，这是TH，色氨酸羟化酶和一氧化氮合酶的必需辅因子。短期注射苯甲酸雌二醇（EB）15或40 μg/kg，间隔12 h，5次，可引起腹侧被盖区（VTA）、黑质（SN）、蓝斑（LC）和孤束核（NTS）多巴胺能和去甲肾上腺素能细胞体TH和GTPCH mRNA水平的增加。雌激素引起的BH 4浓度的变化主要与GTPCH mRNA水平的变化相关，但SN除外。通过注射（EB：25 μg/kg，16次注射，间隔26 h; 50 μg/kg，16次注射，间隔48 h）或颗粒（0.1 mg 17 β-雌二醇，14天）长期给予雌二醇，在除NTS外的大多数位置，对调节两种基因的mRNA水平不是非常有效。EB的长期注射升高了整个NTS和微血管中的GTPCH mRNA水平。雌二醇颗粒给药导致NTS吻内侧TH mRNA下降，尾侧升高。因此，雌二醇以组织特异性方式对TH和GTPCH基因表达具有复杂和不同的作用，并取决于给药方式。
The effect of different dose, mode and duration of estradiol administration was examined in the different brain catecholaminergic areas in ovariectomized (OVX) female rats. We determined changes in mRNA levels of tyrosine hydroxylase (TH), rate-limiting enzyme in catecholamine (CA) biosynthesis of GTP cyclohydrolase I (GTPCH), rate-limiting enzyme in biosynthesis as well as of tetrahydrobiopterin (BH4), and concentration of BH4, which is an essential cofactor for TH, tryptophan hydroxylase and nitric oxide synthase. Short-term administration of estradiol benzoate (EB) by five injections of 15 or 40 μg/kg 12 h apart led to increase in TH and GTPCH mRNA levels in dopaminergic and noradrenergic cell bodies of the ventral tegmental area (VTA), substantia nigra (SN), locus coeruleus (LC) and the nucleus of solitary tract (NTS) depending on dose of administration. Estrogen-elicited alterations in BH4 concentrations were mostly correlated with changes in GTPCH mRNA levels, except in SN. Long-term administration of estradiol by injections (EB: 25 μg/kg, 16 injections 26 h apart; 50 μg/kg, 16 injections 48 h apart) or pellets (0.1 mg 17 β-estradiol, 14 days) were not very effective in modulating mRNA levels for both genes in most locations except the NTS. Long-term injections of EB elevated GTPCH mRNA levels throughout the NTS and in microvessels. Administration of estradiol by pellets led to decline of TH mRNA in rostral-medial and elevation in caudal parts of the NTS. Thus, estradiol has a complex and differential effect on TH and GTPCH gene expression in a tissue specific manner and depends on the mode of administration.