Sex difference in the phosphorylation of cAMP response element binding protein (CREB) in neonatal rat brain
Sex difference in the phosphorylation of cAMP response element binding protein (CREB) in neonatal rat brain
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DOI：
10.1016/s0006-8993(00)03151-6
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发表时间：
2001-01-26
期刊：
影响因子：
2.9
通讯作者：
McCarthy, MM
中科院分区：
文献类型：
--
作者：
Auger, AP;Hexter, DP;McCarthy, MM
在出生当天，雄性大鼠睾丸睾酮释放的激增对于大脑的性别分化至关重要。类固醇激素通过与细胞内类固醇受体结合并改变基因表达来发挥作用;然而，关于在发育中的大脑中类固醇激素作用的结果改变的信号转导途径知之甚少。我们研究了出生时睾酮的增加是否会改变CREB（一种主要的信号转导蛋白）的磷酸化。在出生当天，对雄性和雌性幼仔的相邻脑切片进行丝氨酸（133）磷酸化CREB（pCREB）或总CREB的免疫细胞化学染色。男性有更多的pCREB免疫反应阳性细胞比女性在内侧视前区，下丘脑腹内侧核，弓状核，海马CA 1区，但不是在两个丘脑核。CREB免疫反应阳性细胞总数无性别差异。为了确定pCREB的性别差异是否在出生后持续24小时，以及该差异是否是由于睾酮引起的，用100 μ g丙酸睾酮注射新生雌性幼仔，用溶媒注射雄性和对照雌性幼仔。24小时后，对相邻脑切片进行pCREB或CREB免疫细胞化学染色。我们发现，男性和睾酮治疗的女性有更多的pCREB在腹内侧核的下丘脑相比，对照组女性。在检查的任何其他区域，pCREB或CREB均无组间差异。这些结果表明，睾酮在发育中的大脑中的一些作用是通过与CREB磷酸化相关的途径发生的。(C)2001 Elsevier Science B. V.保留所有权利。
On the day of birth, a surge in testicular testosterone release in male rats is critical for sexual differentiation of the brain. Steroid hormones function by binding to intracellular steroid receptors and altering gene expression; however, little is known about the signal transduction pathways altered as a consequence of steroid hormone action in developing brain. We investigated whether the increase in testosterone at birth alters the phosphorylation of CREB, a major signal transduction protein. Adjacent brain sections from male and female pups were immunocytochemically stained for serine (133) phosphorylated CREB (pCREB) or total CREB on the day of birth. Males had more pCREB-immunoreactive positive cells than females in the medial preoptic area, ventromedial nucleus of the hypothalamus, the arcuate nucleus, and the CA1 region of the hippocampus, but not in two thalamic nuclei. There was no sex difference in total CREB immunoreactive cell number. To determine if the sex difference in pCREB persisted 24 h after birth and whether the difference was due to testosterone, newborn female pups were injected with 100 mug of testosterone propionate, and male and control female pups were injected with vehicle. Twenty-four hours later, adjacent brain sections were immunocytochemically stained for either pCREB or CREB. We found that males and testosterone-treated females had more pCREB in the ventromedial nucleus of the hypothalamus contrasted to control females. There were no group differences in pCREB or CREB in any other area examined. These results indicate that some of the effects of testosterone in developing brain occur via pathways associated with the phosphorylation of CREB. (C) 2001 Elsevier Science B.V. All rights reserved.