Addition of a carboxy-terminal tail to the normally tailless gonadotropin-releasing hormone receptor impairs fertility in female mice.
Addition of a carboxy-terminal tail to the normally tailless gonadotropin-releasing hormone receptor impairs fertility in female mice.
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DOI：
10.7554/elife.72937
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发表时间：
2021-12-23
期刊：
影响因子：
7.7
通讯作者：
Bernard DJ
中科院分区：
文献类型：
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作者：
Toufaily C;Fortin J;Alonso CA;Lapointe E;Zhou X;Santiago-Andres Y;Lin YF;Cui Y;Wang Y;Devost D;Roelfsema F;Steyn F;Hanyaloglu AC;Hébert TE;Fiordelisio T;Boerboom D;Bernard DJ
促性腺激素释放激素（GnRH）是脊椎动物控制生殖的主要神经肽。GnRH通过脑垂体中的G蛋白偶联受体GnRHR刺激促卵泡激素（FSH）和促黄体生成素（LH）的合成。在哺乳动物中，GnRHR缺乏C-末端胞质尾（Ctail），并且不表现出同源脱敏。这可能是一种进化适应，使LH峰产生和排卵。为了验证这一想法，我们在转基因模型中将鸡GnRHR Ctail与内源性鼠GnRHR融合。LH峰被钝化，但在这些小鼠中未被阻断。相反，他们显示FSH产生，卵泡发育和生育能力下降。添加Ctail改变了正常FSH产生所需的激动剂诱导的钙信号传导的性质。在哺乳动物进化过程中GnRHR Ctail的丢失不太可能通过使LH激增而赋予选择性优势。这种专门化的适应意义仍有待确定。
Gonadotropin-releasing hormone (GnRH) is the primary neuropeptide controlling reproduction in vertebrates. GnRH stimulates follicle-stimulating hormone (FSH) and luteinizing hormone (LH) synthesis via a G-protein-coupled receptor, GnRHR, in the pituitary gland. In mammals, GnRHR lacks a C-terminal cytosolic tail (Ctail) and does not exhibit homologous desensitization. This might be an evolutionary adaptation that enables LH surge generation and ovulation. To test this idea, we fused the chicken GnRHR Ctail to the endogenous murine GnRHR in a transgenic model. The LH surge was blunted, but not blocked in these mice. In contrast, they showed reductions in FSH production, ovarian follicle development, and fertility. Addition of the Ctail altered the nature of agonist-induced calcium signaling required for normal FSH production. The loss of the GnRHR Ctail during mammalian evolution is unlikely to have conferred a selective advantage by enabling the LH surge. The adaptive significance of this specialization remains to be determined.