Terasawa E, Busser B W, Luchansky L L, Sherwood N M, Jennes L, Millar R P, Glucksman M J, Roberts J L
Wisconsin Regional Primate Research Center, University of Wisconsin, Madison, Wisconsin 53715-1299, USA.
J Comp Neurol. 2001 Oct 29;439(4):491-504. doi: 10.1002/cne.1364.
Previously, we have shown that two types of luteinizing hormone-releasing hormone (LHRH) -like neurons, "early" and "late" cells, were discernible in the forebrain of rhesus monkey fetuses by using antiserum GF-6, which cross-reacts with several forms of LHRH. The "late" cells that arose from the olfactory placode of monkey fetuses at embryonic days (E) 32-E36, are bona fide LHRH neurons. The "early" cells were found in the forebrain at E32-E34 and settled in the extrahypothalamic area. The molecular form of LHRH in "early" cells differs from "late" cells, because "early" cells were not immunopositive with any specific antisera against known forms of LHRH. In this study, we investigated the molecular form of LHRH in the "early" cells in the nasal regions and brains of 13 monkey fetuses at E35 to E78. In situ hybridization studies suggested that both "early" and "late" LHRH cells expressed mammalian LHRH mRNA. Furthermore, "early" cells predominantly contain LHRH1-5-like peptide and its cleavage enzyme, metalloendopeptidase E.C.3.4.24.15 (EP24.15), which cleaves LHRH at the Tyr5-Gly6 position. This conclusion was based on immunocytochemical labeling with various antisera, including those against LHRH1-5, LHRH4-10, or EP24.15, and on preabsorption tests. Therefore, in primates, a group of neurons containing mammalian LHRH mRNA arises at an early embryonic stage before the migration of bona fide LHRH neurons, and is ultimately distributed in the extrahypothalamic region. These extrahypothalamic neurons contain LHRH fragments, rather than fully mature mammalian LHRH. The origin and function of these neurons remain to be determined.
此前，我们已经表明，通过使用与多种形式的促黄体生成激素释放激素（LHRH）发生交叉反应的抗血清GF-6，在恒河猴胎儿的前脑中可辨别出两种类型的LHRH样神经元，即“早期”细胞和“晚期”细胞。“晚期”细胞在胚胎期（E）32-E36从猴胎儿的嗅基板产生，是真正的LHRH神经元。“早期”细胞在E32-E34时在前脑中被发现，并定居于下丘脑外区域。“早期”细胞中LHRH的分子形式与“晚期”细胞不同，因为“早期”细胞对针对已知形式LHRH的任何特异性抗血清均无免疫阳性反应。在本研究中，我们调查了13只E35至E78猴胎儿的鼻腔区域和大脑中“早期”细胞内LHRH的分子形式。原位杂交研究表明，“早期”和“晚期”LHRH细胞均表达哺乳动物LHRH mRNA。此外，“早期”细胞主要含有LHRH1-5样肽及其裂解酶金属内肽酶E.C.3.4.24.15（EP24.15），该酶在Tyr5-Gly6位置裂解LHRH。这一结论基于用各种抗血清（包括针对LHRH1-5、LHRH4-10或EP24.15的抗血清）进行的免疫细胞化学标记以及预吸收试验。因此，在灵长类动物中，一组含有哺乳动物LHRH mRNA的神经元在真正的LHRH神经元迁移之前的胚胎早期阶段就已出现，并最终分布于下丘脑外区域。这些下丘脑外神经元含有LHRH片段，而非完全成熟的哺乳动物LHRH。这些神经元的起源和功能仍有待确定。
