Leptin induces ovulation in GnRH-deficient mice
Leptin induces ovulation in GnRH-deficient mice
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DOI：
10.1096/fj.04-2271fje
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发表时间：
2004-10-01
期刊：
影响因子：
4.8
通讯作者：
Rubinstein, M
中科院分区：
文献类型：
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作者：
Barkan, D;Hurgin, V;Rubinstein, M
瘦素缺乏的ob/ob小鼠具有促性腺激素释放激素（GnRH）分泌减少，导致促性腺激素缺乏、性腺功能减退和不排卵，这些在瘦素给药后完全逆转。为了确定瘦素在排卵中的作用是否完全通过GnRH介导，我们研究了瘦素在GnRH缺陷（hpg）小鼠，以及ob/ob小鼠和正常青春期前小鼠中的作用，其中GnRH轴被antide阻断。孕马血清促性腺激素预处理后，瘦素诱导排卵在所有三个小鼠模型。与成熟的正常小鼠不同，这些排卵不是由促黄体生成激素（LH）激增引发的，正如其替代标记物孕酮缺乏增加所证明的那样。相反，瘦素诱导卵泡充血和渗漏，以及蛋白酶ADAMTS-1（一种具有血小板反应蛋白样基序的去整合素和金属蛋白酶），这有助于卵泡内容物的挤出。这些数据表明，在其作为GnRH分泌诱导剂的作用之上，瘦素可能引起LH非依赖性排卵。
Leptin-deficient ob/ob mice have reduced gonadotropin-releasing hormone (GnRH) secretion, leading to gonadotropin deficiencies, hypogonadism, and anovulation, which are completely reversed following leptin administration. To determine whether the role of leptin in ovulation is mediated exclusively through GnRH, we studied leptin's action in GnRH-deficient (hpg) mice, as well as ob/ob mice and normal, prepubertal mice in which the GnRH axis was blocked with antide. Following pretreatment with pregnant mare serum gonadotropin, leptin induced ovulation in all three mouse models. Unlike mature normal mice, these ovulations were not triggered by a luteinizing hormone (LH) surge, as demonstrated by lack of increase in its surrogate marker progesterone. Rather, leptin induced hyperemia and leakage in the follicle, as well as the proteinase ADAMTS-1 (a disintegrin and metalloproteinase with a thrombospondin-like motif), which facilitates extrusion of the follicular content. These data show that on top of its role as an inducer of GnRH secretion, leptin may elicit an LH-independent ovulation.