Tena-Sempere M, Navarro J, Pinilla L, González L C, Huhtaniemi I, Aguilar E
Department of Physiology, University of Córdoba, 14004 Córdoba, Spain.
J Endocrinol. 2000 May;165(2):345-57. doi: 10.1677/joe.0.1650345.
The biological actions of estrogens on target cells are mediated by two nuclear receptors: the estrogen receptor (ER) alpha and the recently characterized ER beta. In the male rat, the physiological role of estrogens involves multiple actions, from masculinization of brain areas related to reproductive function and sexual behavior to regulation of testicular development and function. Paradoxically, however, administration of high doses of estrogen during the critical period of neonatal differentiation results in an array of defects in the reproductive axis that permanently disrupt male fertility. The focus of this study was to characterize the effects and mechanism(s) of action of neonatal estrogenization on the pattern of testicular ER alpha and beta gene expression during postnatal development. To this end, groups of male rats were treated at day 1 of age with estradiol benzoate (500 microg/rat), and testicular ER alpha and ER beta mRNA levels were assayed by semi-quantitative RT-PCR from the neonatal period until puberty (days 1-45 of age). Furthermore, the expression of androgen receptor (AR) mRNA was evaluated, given the partially overlapping pattern of tissue distribution of ER alpha, ER beta and AR messages in the developing rat testis. In addition, potential mechanisms for neonatal estrogen action were explored. Thus, to discriminate between direct effects and indirect actions through estrogen-induced suppression of serum gonadotropins, the effects of neonatal estrogenization were compared with those induced by blockade of gonadotropin secretion with a potent LHRH antagonist in the neonatal period. Our results indicate that neonatal exposure to estrogen differentially alters testicular expression of alpha and beta ER messages: ER alpha mRNA levels, as well as those of AR, were significantly decreased, whereas relative and total expression levels of ER beta mRNA increased during postnatal/prepubertal development after neonatal estrogen exposure, a phenomenon that was not mimicked by LHRH antagonist treatment. It is concluded that the effect of estrogen on the expression levels of ER alpha and beta mRNAs probably involves a direct action on the developing testis, and cannot be attributed to estrogen-induced suppression of gonadotropin secretion during the neonatal period.
雌激素受体（ER）α和最近鉴定出的ERβ。在雄性大鼠中，雌激素的生理作用涉及多种行为，从与生殖功能和性行为相关的脑区男性化到睾丸发育和功能的调节。然而，矛盾的是，在新生儿分化的关键时期给予高剂量雌激素会导致生殖轴出现一系列缺陷，从而永久性地破坏雄性生育能力。本研究的重点是表征新生儿雌激素化对出生后发育过程中睾丸ERα和β基因表达模式的作用及其机制。为此，在出生第1天给雄性大鼠组注射苯甲酸雌二醇（500微克/只），并通过半定量逆转录聚合酶链反应（RT-PCR）测定从新生儿期到青春期（出生后1至45天）睾丸ERα和ERβ的mRNA水平。此外，鉴于在发育中的大鼠睾丸中ERα、ERβ和雄激素受体（AR）信息的组织分布模式部分重叠，对AR mRNA的表达进行了评估。此外，还探索了新生儿雌激素作用的潜在机制。因此，为了区分直接作用和通过雌激素诱导的血清促性腺激素抑制产生的间接作用，将新生儿雌激素化的作用与在新生儿期用强效促性腺激素释放激素（LHRH）拮抗剂阻断促性腺激素分泌所诱导的作用进行了比较。我们的结果表明，新生儿暴露于雌激素会不同程度地改变睾丸中α和β ER信息的表达：ERα mRNA水平以及AR的mRNA水平显著降低，而在新生儿期暴露于雌激素后，出生后/青春期前发育过程中ERβ mRNA的相对和总表达水平增加，这一现象未被LHRH拮抗剂治疗所模拟。得出的结论是，雌激素对ERα和β mRNA表达水平的影响可能涉及对发育中睾丸的直接作用，而不能归因于新生儿期雌激素诱导的促性腺激素分泌抑制。
