Relaxin-like factor (RLF) serum concentrations and gubernaculum RLF receptor display in relation to pre- and neonatal development of rats.
Relaxin-like factor (RLF) serum concentrations and gubernaculum RLF receptor display in relation to pre- and neonatal development of rats.
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DOI：
10.1530/rep.0.1220899
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发表时间：
2001-12
期刊：
影响因子：
3.8
通讯作者：
FR Boockfor;G. Fullbright;E. Büllesbach;Christian Schwabe
中科院分区：
文献类型：
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作者：
FR Boockfor;G. Fullbright;E. Büllesbach;Christian Schwabe
小鼠松弛素样因子（RLF）基因的缺失会导致睾丸滞留和不育。合成 RLF 的发展使得研究连接基因组事件和导致性腺定位的基本生物反应的事件成为可能。针对合成 RLF 产生抗 RLF 抗体，从而可以确定关键时期的 RLF 浓度，测试结节上的 RLF 受体，并探索发育中大鼠中受体展示和睾丸迁移之间的时间关系。雄性幼鼠的血清RLF浓度在分娩前第2天较高(2.4 ng ml(-1))，并在分娩前急剧下降。此后，雄性和雌性的血清浓度相同，直到仅雄性的RLF浓度开始增加，从分娩后第10天开始，一直持续到分娩后第39天达到成人RLF浓度（0.6 ng ml(-1)）。在 RLF 浓度增加的这个阶段，睾丸下降到阴囊，并在分娩后第 19-21 天、成人激素浓度建立之前完全下降。产前血清 RLF 浓度高与结节组织中 RLF 受体的高表达相一致。从不同发育阶段的大鼠肾盂制备的每毫克膜蛋白 RLF 的竞争性结合表明，随着性成熟的到来，受体密度没有增加。与对照相比，原代培养物中的结节细胞在 RLF 存在的情况下显示出对 5-溴-2'-脱氧尿苷的摄取增加。这些研究表明，合成的 RLF 具有生物活性，并表明隐睾表型 INSL3(-/-) 是由于发育早期阶段 RLF 缺失而导致的生殖器生长缺陷的直接后果。
Deletion of the relaxin-like factor (RLF) gene in mice causes retention of testicles and infertility. The development of a synthetic RLF has made it possible to investigate the events that connect the genomic event and the basic biological responses that cause gonadal positioning. Anti-RLF antibodies were raised against synthetic RLF, allowing determination of RLF concentrations during the critical period, testing for RLF receptors on the gubernaculum and exploration of the temporal relationship between receptor display and migration of the testes in developing rats. In male rat pups, serum RLF concentrations were high at day 2 before parturition (2.4 ng ml(-1)) and decreased sharply just before parturition. Thereafter, males and females had the same low serum concentrations until RLF concen-trations began to increase in males only, starting at day 10 after parturition and continuing until adult RLF concentrations (0.6 ng ml(-1)) were reached on day 39 after parturition. The testicles are descending into the scrotum during this phase of increasing RLF concentrations and are descended fully by day 19-21 after parturition, before adult hormone concentrations are established. The high prenatal serum RLF concentration coincides with high expression of RLF receptors in the gubernaculum tissue. Competitive binding of RLF per mg of membrane protein prepared from rat gubernacula at various developmental stages showed no increase in receptor density as sexual maturity was reached. Gubernaculum cells in primary culture showed an increased uptake of 5-bromo-2'-deoxyuridine in the presence of RLF compared with controls. These studies demonstrate that the synthetic RLF is biologically active and indicate that the cryptorchid phenotype INSL3(-/-) is a direct consequence of defective gubernaculum growth, caused by the absence of RLF during early phases of development.