Dissen G A, Romero C, Hirshfield A N, Ojeda S R
Division of Neuroscience, Oregon Regional Primate Research Center/Oregon Health Science University, Beaverton, Oregon 97006-3448, USA.
Endocrinology. 2001 May;142(5):2078-86. doi: 10.1210/endo.142.5.8126.
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.
神经生长因子（NGF）是神经营养因子（NTs）家族的典型代表，而神经营养因子是中枢和外周神经系统中神经元存活及分化所必需的。外周神经系统支配的组织中NGF的合成与其作为靶源性营养因子的功能相一致。然而，性腺中存在低亲和力和高亲和力的NGF受体，这提示神经营养因子在生殖内分泌系统中具有另一功能。我们现在报告，原始卵泡的生长需要NGF，而这一过程已知是独立于垂体促性腺激素发生的。在正常幼鼠及携带NGF基因无效突变的小鼠卵巢中均发现神经营养因子受体p75（NTR）和NGF酪氨酸激酶受体trkA表达。在卵巢组织发生完成后分析纯合子NGF基因敲除（-/-）突变动物的卵巢，发现在血清促性腺激素水平正常的情况下，初级和次级卵泡数量明显减少，未被纳入卵泡结构的卵母细胞数量增加。使用两种互补的增殖标记物评估有丝分裂活性，发现NGF缺陷小鼠卵巢中的体细胞增殖显著减少。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缺失有关。
