Department of Zoology, The University of Melbourne, Melbourne, Victoria 3010, Australia.
Reproduction. 2010 Mar;139(3):599-611. doi: 10.1530/REP-09-0305. Epub 2009 Dec 22.
Oestrogen has wide ranging effects in development mediated mainly via the two oestrogen receptors, alpha (ESR1, also known as ERalpha) and beta (ESR2, also known as ERbeta). Oestrogen is the key factor that directs the indifferent gonad to become an ovary in many non-mammalian vertebrates. Oestrogen is not required for early ovarian differentiation in mammals but can disrupt normal testicular development in eutherians. Surprisingly, exogenous oestrogen can cause sex reversal of an XY gonad in two marsupials, the North American opossum and the tammar wallaby. To understand the mechanism by which oestrogen induces sex reversal, we characterised the genes for ESR1 and ESR2 and examined their expression during gonadal differentiation in the tammar wallaby, Macropus eugenii. Both receptors were expressed in the somatic cells and germ cells of the indifferent gonad in both XX and XY foetuses throughout all stages of development, and persisted in these cells into adulthood. ERs were also present in many other tissues including kidney, pituitary and mammary gland. ER mRNA was not significantly altered by exogenous oestrogen in cultured XY gonads but the receptors translocated to the nucleus in its presence. These findings confirm that there is conserved expression of the ERs in the indifferent gonad despite the lack of available ligand during early gonadal development. The receptors can respond to exogenous estrogen at this early stage and are capable of transducing signals in the early mammalian gonad. However, the selective forces that maintained conserved ER expression in this tissue remain unknown.
雌激素在发育过程中有广泛的影响,主要通过两种雌激素受体,α(ESR1,也称为 ERalpha)和β(ESR2,也称为 ERbeta)介导。雌激素是指导许多非哺乳动物的中性性腺发育成卵巢的关键因素。雌激素不是哺乳动物早期卵巢分化所必需的,但可以破坏真兽类的正常睾丸发育。令人惊讶的是,外源性雌激素可以导致两种有袋动物,北美的负鼠和塔马尔袋鼠的 XY 性腺性反转。为了了解雌激素诱导性反转的机制,我们对 ESR1 和 ESR2 的基因进行了特征描述,并在塔马尔袋鼠,Macropus eugenii 的性腺分化过程中检查了它们的表达。在 XX 和 XY 胎儿的所有发育阶段,两种受体都在中性性腺的体细胞和生殖细胞中表达,并且在这些细胞中一直持续到成年期。ER 也存在于许多其他组织中,包括肾脏、垂体和乳腺。外源性雌激素在培养的 XY 性腺中对 ER mRNA 没有明显影响,但在其存在下,受体转移到核内。这些发现证实,尽管在早期性腺发育过程中缺乏可用的配体,但 ER 在中性性腺中仍有保守表达。在这个早期阶段,受体可以对外源性雌激素做出反应,并能够在早期哺乳动物性腺中传递信号。然而,维持这种组织中保守的 ER 表达的选择压力仍然未知。