Nerve growth factor is required for early follicular development in the mammalian ovary.
Nerve growth factor is required for early follicular development in the mammalian ovary.
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DOI：
10.1210/endo.142.5.8126
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发表时间：
2001-05
期刊：
影响因子：
4.8
通讯作者：
G. Dissen;Carmen Romero;A. Hirshfield;S. Ojeda
中科院分区：
文献类型：
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作者：
G. Dissen;Carmen Romero;A. Hirshfield;S. Ojeda
神经生长因子（NGF）是神经营养因子（NTs）蛋白家族的缩影，是中枢和周围神经系统中神经元存活和分化所必需的。周围神经系统支配的组织中神经生长因子的合成与其作为靶源性营养因子的功能是一致的。然而，性腺中存在的低亲和力和高亲和力的NGF受体表明，NTs在生殖内分泌系统中具有另一种功能。我们现在报道，NGF是原始卵巢卵泡生长所必需的，这一过程已知独立于垂体促性腺激素发生。NT受体p75（NTR）和NGF酪氨酸激酶受体trkA在正常幼鼠和NGF基因零突变小鼠卵巢中均有表达。纯合子ngf缺失（-/-）突变动物的卵巢，在卵巢组织发生完成后进行分析，在血清促性腺激素水平正常的情况下，原发性和继发性卵泡数量明显减少，而卵母细胞数量增加，无法融入卵泡结构。利用两种互补的增殖标记物评估有丝分裂活性，发现ngf缺陷小鼠卵巢中体细胞增殖明显减少。这些结果表明，在NGF（-/-）小鼠中观察到的卵泡生长延迟可能与NGF向卵巢非神经内分泌成分提供的增殖信号的丧失有关。
Nerve growth factor (NGF) epitomizes a family of proteins known as the neurotrophins (NTs), which are required for the survival and differentiation of neurons within both the central and peripheral nervous system. Synthesis of NGF in tissues innervated by the peripheral nervous system is consistent with its function as a target-derived trophic factor. However, the presence of low- and high-affinity NGF receptors in the gonads suggests another function for the NTs within the reproductive endocrine system. We now report that NGF is required for the growth of primordial ovarian follicles, a process known to occur independently of pituitary gonadotropins. Both the NT receptor p75(NTR) and the NGF tyrosine kinase receptor trkA were found to be expressed in the ovaries of infantile normal mice and mice carrying a null mutation of the NGF gene. The ovaries from homozygote NGF-null (-/-) mutant animals, analyzed after completion of ovarian histogenesis, exhibited a markedly reduced population of primary and secondary follicles in the presence of normal serum gonadotropin levels, and an increased number of oocytes that failed to be incorporated into a follicular structure. Assessment of mitogenic activity using two complementary proliferation markers revealed a conspicuous reduction in somatic cell proliferation in the ovaries of NGF-deficient mice. These results suggest that the delay in follicular growth observed in NGF(-/-) mice may be related to the loss of a proliferative signal provided by NGF to the nonneural endocrine component of the ovary.