Rücker Bárbara, Pochmann Daniela, Fürstenau Cristina Ribas, Carneiro-Ramos Marcela Sorelli, Battastini Ana Maria Oliveira, Barreto-Chaves Maria Luiza M, Sarkis João José Freitas
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Gen Comp Endocrinol. 2005 Jan 15;140(2):94-100. doi: 10.1016/j.ygcen.2004.10.008. Epub 2004 Nov 24.
Over the last few years, the effects of steroid hormones on the brain have been intensively discussed. It has been demonstrated that ATP (acting as a neurotransmitter) is hydrolyzed to adenosine in the synaptic cleft by the conjugated action of ectonucleotidases, which include an enzyme of the E-NTPDase family (NTPDase3, apyrase, EC 3.6.1.5) and a 5'-nucleotidase (EC 3.1.3.5). The 5'-nucleotidase enzyme is able to hydrolyze AMP as well as other monophosphate nucleotides. The importance of this enzyme in the central nervous system is to participate in the adenosine formation, a nucleoside with neuroprotective properties and modulatory effects. However, several questions have been raised about the mechanisms of steroid hormones and the possible neuroprotective effects of estrogen. Thus, we examined the effects of gonadal steroid hormone deprivation, induced by ovary removal (OVX) and estradiol replacement therapy, on the ectonucleotidase activities in synaptosomes from hippocampus and cerebral cortex of adult rats. ATP and ADP hydrolysis in synaptosomes from cerebral cortex and hippocampus did not change as a function of OVX and results demonstrated an increase in AMP hydrolysis (82%) in the animals submitted to OVX in cerebral cortex, but not in hippocampus, when compared to control and sham-operated groups. Estradiol replacement therapy reversed this effect. RT-PCR analysis showed that the enhancement of enzyme activity in cerebral cortex could be explained by the higher expression of 5'-nucleotidase, following OVX. The hormones 17beta-estradiol (cyclodextrin-encapsulated 17beta-estradiol), DHEAS, and pregnenolone (1.0, 2.5, and 5.0 microM) did not alter the nucleotide hydrolysis, in vitro, in synaptosomes from cortex and hippocampus of female adult rats. Results presented, herein, should be considered relevant for hormone replacement therapy, since much controversy exists surrounding this area and the relationship between adenosine and sex steroids is still poorly understood.
在过去几年中，类固醇激素对大脑的影响一直是人们深入讨论的话题。已经证明，ATP（作为一种神经递质）在外核苷酸酶的协同作用下于突触间隙中水解为腺苷，外核苷酸酶包括E-NTPDase家族的一种酶（NTPDase3，腺苷三磷酸双磷酸酶，EC 3.6.1.5）和一种5'-核苷酸酶（EC 3.1.3.5）。5'-核苷酸酶能够水解AMP以及其他单磷酸核苷酸。该酶在中枢神经系统中的重要性在于参与腺苷的形成，腺苷是一种具有神经保护特性和调节作用的核苷。然而，关于类固醇激素的作用机制以及雌激素可能的神经保护作用，人们提出了几个问题。因此，我们研究了成年大鼠卵巢切除（OVX）诱导的性腺类固醇激素剥夺以及雌二醇替代疗法对海马体和大脑皮质突触体中外核苷酸酶活性的影响。大脑皮质和海马体突触体中ATP和ADP的水解并未随OVX而发生变化，结果表明，与对照组和假手术组相比，接受OVX的动物大脑皮质中AMP水解增加了82%，但海马体中未增加。雌二醇替代疗法逆转了这种效应。RT-PCR分析表明，OVX后大脑皮质中酶活性的增强可以通过5'-核苷酸酶的更高表达来解释。激素17β-雌二醇（环糊精包裹的17β-雌二醇）、硫酸脱氢表雄酮和孕烯醇酮（1.0、2.5和5.0微摩尔）在体外并未改变成年雌性大鼠皮质和海马体突触体中的核苷酸水解。本文给出的结果应被视为与激素替代疗法相关，因为围绕这一领域存在诸多争议，腺苷与性类固醇之间的关系仍未得到充分理解。
