Department of Psychology, Behavioral Neuroscience Program, University at Albany - State University of New York, Albany, NY 12222, USA.
J Neuroendocrinol. 2012 Feb;24(2):285-91. doi: 10.1111/j.1365-2826.2011.02232.x.
Steroid hormones largely exert their actions by activating nuclear receptors, which, as transcription factors, powerfully influence fundamental processes of neural development. Often, steroid receptor action demonstrates remarkable specificity under different developmental, anatomical or hormonal conditions. Yet, the mechanisms underlying such specificity are poorly understood. The present study examined the anatomically-specific regulation of progestin receptor (PR) expression by oestrogen receptor (ER) activation in the ventromedial nucleus (VMN) of the hypothalamus and the medial preoptic nucleus (MPN) of the neonatal female rat brain, using the selective oestrogen receptor modulators (SERMs), tamoxifen and ICI 182780 (ICI), in the presence or absence of oestradiol benzoate (EB) treatment. The results demonstrate that PR immunoreactivity (PR-ir) in the neonatal female MPN was significantly increased by EB and this increase was abolished by either tamoxifen or ICI treatment. In contrast, within the VMN of the same animals, EB had no effect on PR-ir and the SERMs only modestly decreased PR-ir. Interestingly, ICI acted as a true antagonist regardless of EB treatment, whereas tamoxifen acted as an ER agonist in the absence of EB in the MPN, but not the VMN, representing one of the first in vivo demonstrations of tissue-specific and oestradiol-independent effects of tamoxifen on ER activation. The present results indicate that PR expression is highly dependent on oestradiol and its receptor in the MPN, although it is independent of both oestradiol and ER activation within the neonatal VMN. These findings demonstrate the anatomically-specific actions of oestradiol and its receptor to induce PR in two brain regions controlling different aspects of female reproductive behaviours in adulthood.
甾体激素主要通过激活核受体发挥作用，核受体作为转录因子，有力地影响神经发育的基本过程。通常，甾体激素受体在不同的发育、解剖或激素条件下表现出显著的特异性。然而，这种特异性的机制还知之甚少。本研究使用选择性雌激素受体调节剂（SERMs），他莫昔芬和 ICI 182780（ICI），在存在或不存在苯甲酸雌二醇（EB）处理的情况下，检查了雌激素受体（ER）激活对下丘脑腹内侧核（VMN）和新生雌性大鼠脑内侧视前核（MPN）中孕激素受体（PR）表达的解剖特异性调节。结果表明，EB 显著增加了新生雌性大鼠 MPN 中的 PR 免疫反应性（PR-ir），而这种增加被他莫昔芬或 ICI 处理所消除。相比之下，在同一动物的 VMN 中，EB 对 PR-ir 没有影响，SERMs 仅适度降低 PR-ir。有趣的是，ICI 无论是否存在 EB 处理，都作为一种真正的拮抗剂起作用，而他莫昔芬在 MPN 中没有 EB 的情况下作为 ER 激动剂起作用，但在 VMN 中不起作用，这代表了他莫昔芬对 ER 激活的组织特异性和雌激素非依赖性作用的首次体内证明之一。本研究结果表明，PR 表达在 MPN 中高度依赖于雌激素及其受体，尽管在控制成年女性生殖行为不同方面的两个脑区 VMN 中，PR 表达独立于雌激素和 ER 激活。这些发现表明，雌激素及其受体在两个脑区中的解剖特异性作用，可诱导 PR 表达，从而控制成年女性生殖行为的不同方面。
