Ojeda S R, Dissen G A, Junier M P
Division of Neuroscience, Oregon Regional Primate Research Center, Beaverton 97006.
Front Neuroendocrinol. 1992 Apr;13(2):120-62.
The concept is proposed that polypeptide neurotrophic factors contribute to the developmental regulation of ovarian and hypothalamic function in mammals. Nerve growth factor (NGF) and neurotrophin-3, two members of the neurotrophin family, have been identified in the rat ovary and one of its receptors has been localized to the innervation and thecal cells of developing follicles. Although NGF supports the sympathetic innervation of the gland, the extent to which follicles are innervated appears to be defined by the differential expression of NGF receptors in the theca of developing follicles. The presence of NGF receptors in steroid-producing cells suggests a direct involvement of neurotrophins in the regulation of gonadal endocrine function. Evidence is beginning to emerge suggesting that development of the reproductive hypothalamus is affected by insulin-like growth factor 1 secreted by peripheral tissues, and transforming growth factor alpha (TGF alpha) produced locally. In the rat hypothalamus, TGF alpha appears to be synthesized in both neurons and glial cells. In glial cells it may interact with epidermal growth factor (EGF) receptors to further enhance TGF alpha synthesis and to, perhaps, stimulate eicosanoid formation. In turn, one of these eicosanoids, prostaglandin E2, may act on luteinizing hormone-releasing hormone (LHRH) neurons to stimulate the release of LHRH in a genomic-independent manner. This provides the basis for the notion that during development LHRH secretion is regulated by a dual mechanism, one that involves transsynaptic effects exerted by neurotransmitters, the other that requires a glial-neuronal interaction and that may predominantly regulate release of the neuropeptide. An increased expression of the TGF alpha and EGF receptor genes in reactive astrocytes is postulated to contribute to the process by which hypothalamic injury causes sexual precocity. Morphological maturation of the reproductive hypothalamus is thought to occur during sexual development. The process is accelerated by estradiol, which exerts its neurotrophic effects by enhancing the expression of genes encoding cytoskeletal proteins involved in neuronal development and regeneration. It is suggested that acquisition of functional competence by both the ovaries and the reproductive hypothalamus requires the participation of specific, but not similar, neurotrophic factors. The relevance of these concepts to the process of sexual development in other species, particularly primates, remains to be defined.
提出了一种概念，即多肽神经营养因子有助于哺乳动物卵巢和下丘脑功能的发育调节。神经营养因子家族的两个成员，神经生长因子（NGF）和神经营养素-3，已在大鼠卵巢中被鉴定出来，并且其一种受体已定位在发育卵泡的神经支配和卵泡膜细胞中。尽管NGF支持腺体的交感神经支配，但卵泡的神经支配程度似乎由发育卵泡卵泡膜中NGF受体的差异表达所决定。类固醇生成细胞中存在NGF受体表明神经营养素直接参与性腺内分泌功能的调节。越来越多的证据表明，生殖下丘脑的发育受到外周组织分泌的胰岛素样生长因子1和局部产生的转化生长因子α（TGFα）的影响。在大鼠下丘脑中，TGFα似乎在神经元和神经胶质细胞中均有合成。在神经胶质细胞中，它可能与表皮生长因子（EGF）受体相互作用，以进一步增强TGFα的合成，并可能刺激类花生酸的形成。反过来，这些类花生酸之一，前列腺素E2，可能作用于促黄体生成素释放激素（LHRH）神经元，以非基因组依赖的方式刺激LHRH的释放。这为以下观点提供了基础，即在发育过程中，LHRH的分泌受双重机制调节，一种机制涉及神经递质施加的跨突触效应，另一种机制需要神经胶质-神经元相互作用，并且可能主要调节神经肽的释放。推测反应性星形胶质细胞中TGFα和EGF受体基因表达的增加有助于下丘脑损伤导致性早熟的过程。生殖下丘脑的形态成熟被认为发生在性发育期间。该过程由雌二醇加速，雌二醇通过增强参与神经元发育和再生的细胞骨架蛋白编码基因的表达来发挥其神经营养作用。有人提出，卵巢和生殖下丘脑获得功能能力需要特定但不相似的神经营养因子的参与。这些概念与其他物种，特别是灵长类动物性发育过程的相关性仍有待确定。
