Le Saux Maryvonne, Di Paolo Thérèse
Molecular Endocrinology and Oncology Research Center, Faculté de Pharmacie, Laval University Medical Center (CHUL), 2705, Laurier Boulevard, Sainte-Foy, Que., Canada G1V 4G2.
Psychoneuroendocrinology. 2005 Apr;30(3):251-60. doi: 10.1016/j.psyneuen.2004.08.002.
Estrogens modulate the expression of preproenkephalin (PPE) in the hypothalamus but little is known for other brain regions. The present study investigated the effect of hormonal withdrawal and replacement therapy on PPE expression in the striatum, nucleus accumbens and cortex. Ovariectomized Sprague-Dawley rats were treated for 2 weeks with estradiol, a specific ligand for estrogen receptor alpha (ERalpha), 4,4',4''-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (PPT) and estrogen receptor beta (ERbeta) 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN), or the selective estrogen receptor modulators (SERMs) tamoxifen and raloxifene. Brain PPE mRNA levels, measured by in situ hybridization, were high in the striatum and nucleus accumbens compared to the low expression in the cortex. Ovariectomy decreased uterine weights compared to intact uterus, which was corrected by estradiol and PPT. Tamoxifen and raloxifene partially stimulated uterine weights while DPN left it unchanged. In the anterior, median and posterior striatum and in the core and shell of the nucleus accumbens, ovariectomy decreased PPE mRNA levels compared to intact rats, this was corrected by estradiol treatment except for the posterior striatum. PPT, DPN, tamoxifen and raloxifene reproduced the estradiol effect. In the prefrontal and cingulate cortices, neither ovariectomy nor treatments changed PPE mRNA levels. These results show for the first time that estradiol increases PPE mRNA in the striatum and nucleus accumbens. This effect is observed also with estrogen receptor agonists for the ERalpha and ERbeta as well as with SERMs.
雌激素可调节下丘脑前脑啡肽原（PPE）的表达，但对其他脑区的情况知之甚少。本研究调查了激素撤退和替代疗法对纹状体、伏隔核和皮质中PPE表达的影响。对去卵巢的斯普拉格-道利大鼠用雌二醇（一种雌激素受体α（ERα）的特异性配体）、4,4',4''-(4-丙基-[1H]-吡唑-1,3,5-三基)三苯酚（PPT）和雌激素受体β（ERβ）2,3-双(4-羟基苯基)-丙腈（DPN），或选择性雌激素受体调节剂（SERM）他莫昔芬和雷洛昔芬进行为期2周的治疗。通过原位杂交测量的脑PPE mRNA水平，与皮质中的低表达相比，纹状体和伏隔核中的水平较高。与完整子宫相比，去卵巢降低了子宫重量，而雌二醇和PPT可纠正这一情况。他莫昔芬和雷洛昔芬部分刺激了子宫重量，而DPN使其保持不变。在前、中、后纹状体以及伏隔核的核心和壳部，与完整大鼠相比，去卵巢降低了PPE mRNA水平，除后纹状体外，雌二醇治疗可纠正这一情况。PPT、DPN、他莫昔芬和雷洛昔芬重现了雌二醇的作用。在额叶和扣带回皮质中，去卵巢和治疗均未改变PPE mRNA水平。这些结果首次表明，雌二醇可增加纹状体和伏隔核中的PPE mRNA。雌激素受体α和β的激动剂以及SERM也观察到了这种作用。
