ERK Signaling in the Pituitary Is Required for Female But Not Male Fertility
ERK Signaling in the Pituitary Is Required for Female But Not Male Fertility
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DOI：
10.1210/me.2009-0030
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发表时间：
2009-07-01
影响因子：
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通讯作者：
Roberson, Mark S.
中科院分区：
文献类型：
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作者：
Bliss, Stuart P.;Miller, Andrew;Roberson, Mark S.
男性和女性需要不同模式的垂体促性腺激素分泌的生育能力。这些垂体激素生产的性别特异性配置文件的机制是未知的，但是，他们是根本的了解在分子水平上的生殖功能的性二态控制。一些研究表明，ERK 1和-2是下丘脑GnRH介导的垂体促性腺激素产生和生育调节的重要调节剂。为了验证这一假设，我们产生了一个垂体特异性耗竭ERK 1和2的小鼠，并检查了一系列生理参数，包括生育能力。我们发现雌性排卵和生育需要ERK信号，而雄性生殖功能不受这种信号缺陷的影响。ERK途径消融对LH生物合成的影响是这种性别特异性表型的基础，其分子机制涉及需要ERK依赖性上调转录因子Egr 1，这是LH β表达所必需的。总之，这些发现代表了一个重要的进展，阐明性别特异性调节下丘脑-垂体-性腺轴和性二态控制生育的分子基础。（分子内分泌学23：1092-1101，2009）
Males and females require different patterns of pituitary gonadotropin secretion for fertility. The mechanisms underlying these gender-specific profiles of pituitary hormone production are unknown; however, they are fundamental to understanding the sexually dimorphic control of reproductive function at the molecular level. Several studies suggest that ERK1 and -2 are essential modulators of hypothalamic GnRH-mediated regulation of pituitary gonadotropin production and fertility. To test this hypothesis, we generated mice with a pituitary-specific depletion of ERK1 and 2 and examined a range of physiological parameters including fertility. We find that ERK signaling is required in females for ovulation and fertility, whereas male reproductive function is unaffected by this signaling deficiency. The effects of ERK pathway ablation on LH biosynthesis underlie this gender-specific phenotype, and the molecular mechanism involves a requirement for ERK-dependent up-regulation of the transcription factor Egr1, which is necessary for LH beta expression. Together, these findings represent a significant advance in elucidating the molecular basis of gender-specific regulation of the hypothalamic-pituitary-gonadal axis and sexually dimorphic control of fertility. ( Molecular Endocrinology 23: 1092-1101, 2009)