Immunocytochemical investigation of nuclear progestin receptor expression within dopaminergic neurones of the female rat brain.
Immunocytochemical investigation of nuclear progestin receptor expression within dopaminergic neurones of the female rat brain.
复制标题
雌性大鼠脑多巴胺能神经元内核孕激素受体表达的免疫细胞化学研究。
DOI：
10.1111/j.1365-2826.2004.01198.x
复制
发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Blaustein,JD
中科院分区：
文献类型：
--
作者：
Lonstein,JS;Blaustein,JD
黄体酮影响女性生殖的大多数过程，包括排卵、性行为、怀孕、分娩、哺乳和母性行为。黄体酮可能通过一种神经递质来调节这些功能，这种递质就是多巴胺。为了确定大脑中孕酮可能通过细胞核黄体酮受体改变大鼠这些过程和其他过程所必需的多巴胺能活性，将去卵巢的大鼠皮下注射4µg苯甲酸雌二醇以诱导下丘脑黄体酮受体的高水平表达，或注射油，并在48小时后灌注。双标记免疫细胞化学用于观察对黄体酮受体和酪氨酸羟化酶（一种限制多巴胺合成速率的酶）具有免疫反应性（ir）的细胞。在雌二醇处理的女性脑室周围下丘脑中发现了许多含有黄体酮受体- ir和酪氨酸羟化酶- ir的细胞。相反，油处理对照组的下丘脑中很少有细胞含有黄体酮受体- ir，因此，在该组中很少发现双标记细胞。在雌二醇处理的女性中，表达黄体酮受体的酪氨酸羟化酶免疫反应细胞的比例最大的是在弓形核内或附近（A12组），其中高达55%的酪氨酸羟化酶表达细胞共表达黄体酮受体。值得注意的是，在雌二醇处理的女性中，双标记细胞也被发现比以前报道的更明显，在视前区/下丘脑前部（A14组）大约15-20%的酪氨酸羟化酶- ir细胞也含有黄体酮受体- ir。由于在这些部位很少或没有发现黄体酮受体- ir，因此在下丘脑后嗅部（A11组）、无尾带（A13组）、脑后野（A8组）、腹侧被盖区（A10组）或黑质（A9组）均未发现双标记细胞。这些数据为黄体酮可能调节视前区/下丘脑前部多巴胺释放的神经基质提供了新的信息。使用比以前更灵敏的技术，他们还证实了弓形核中黄体酮受体和酪氨酸羟化酶之间的关系，这可能对调节整个女性生殖周期的催乳素释放很重要。此外，虽然黄体酮改变了中边缘和黑质纹状体多巴胺的释放，以及这些途径影响的许多行为，但这些数据再次表明，黄体酮不是通过腹侧被盖区和黑质多巴胺能细胞中的黄体酮核受体来实现的。
Progesterone influences most processes involved in female reproduction, including ovulation, sexual behaviour, pregnancy, parturition, lactation and maternal behaviour. One neurotransmitter through which progesterone might regulate many of these functions is dopamine. To determine where in the brain progesterone might alter dopaminergic activity necessary for these and other processes in rats via cell nuclear progestin receptors, ovariectomized rats were injected subcutaneously with either 4 µg oestradiol benzoate to induce high levels of hypothalamic progestin receptor expression, or oil, and perfused 48 h later. Dual‐label immunocytochemistry was used to visualize cells having immunoreactivity (ir) for progestin receptors and tyrosine hydroxylase, a rate‐limiting enzyme for dopamine synthesis. Many cells containing both progestin receptor‐ir and tyrosine hydroxylase‐ir were found throughout the periventricular hypothalamus of oestradiol‐treated females. Conversely, very few cells in the hypothalamus of oil‐treated controls contained progestin receptor‐ir and, consequently, few dual‐labelled cells were found in this group. The greatest percentage of tyrosine hydroxylase immunoreactive cells expressing progestin receptors in oestradiol‐treated females was in, or near, the arcuate nucleus (A12 group), where up to 55% of tyrosine hydroxylase‐expressing cells coexpressed progestin receptors. Notably, dual‐labelled cells in oestradiol‐treated females were also found more rostrally than previously reported, with approximately 15–20% of tyrosine hydroxylase‐ir cells in the preoptic area/anterior hypothalamus (A14 group) also containing progestin receptor‐ir. No dual‐labelled cells were found for either group in the posterodorsal hypothalamus (A11 group), zona incerta (A13 group), retrorubral field (A8 group), ventral tegmental area (A10 group) or substantia nigra (A9 group) because little or no progestin receptor‐ir was found in these sites. These data provide new information about the neural substrate where progesterone might regulate dopamine release in the preoptic area/anterior hypothalamus. Using more sensitive techniques than those used previously, they also confirm the relationship between progestin receptor and tyrosine hydroxylase in the arcuate nucleus, which could be important for the regulation of prolactin release throughout the female reproductive cycle. Additionally, although progesterone alters mesolimbic and nigrostriatal dopamine release, and the numerous behaviours that these pathways influence, these data again suggest that it does not do so via nuclear progestin receptor in dopaminergic cells of the ventral tegmental area and substantia nigra.