Osheroff P L, Phillips H S
Department of Protein Chemistry, Genentech, Inc., South San Francisco, CA 94080.
Proc Natl Acad Sci U S A. 1991 Aug 1;88(15):6413-7. doi: 10.1073/pnas.88.15.6413.
Relaxin is a member of the insulin family of polypeptide hormones and exerts its best understood actions in the mammalian reproductive system. Using a biologically active 32P-labeled human relaxin, we have previously shown by in vitro autoradiography specific relaxin binding sites in rat uterus, cervix, and brain tissues. Using the same approach, we describe here a detailed localization of human relaxin binding sites in the rat brain. Displaceable relaxin binding sites are distributed in discrete regions of the olfactory system, neocortex, hypothalamus, hippocampus, thalamus, amygdala, midbrain, and medulla of the male and female rat brain. Characterization of the relaxin binding sites in the subfornical organ and neocortex reveals a single class of high-affinity sites (Kd = 1.4 nM) in both regions. The binding of relaxin to two of the circumventricular organs (subfornical organ and organum vasculosum of the lamina terminalis) and the neurosecretory magnocellular hypothalamic nuclei (i.e., paraventricular and supraoptic nuclei) provides the anatomical and biochemical basis for emerging physiological evidence suggesting a central role for relaxin in the control of blood pressure and hormone release. We conclude that specific, high-affinity relaxin binding sites are present in discrete regions of the rat brain and that the distribution of some of these sites may be consistent with a role for relaxin in control of vascular volume and blood pressure.
松弛素是多肽激素胰岛素家族的一员,在哺乳动物生殖系统中发挥着目前了解最为透彻的作用。我们先前使用具有生物活性的32P标记的人松弛素,通过体外放射自显影法在大鼠子宫、子宫颈和脑组织中发现了特异性松弛素结合位点。采用相同方法,我们在此描述了人松弛素结合位点在大鼠脑中的详细定位。可置换的松弛素结合位点分布于雄性和雌性大鼠脑的嗅觉系统、新皮层、下丘脑、海马体、丘脑、杏仁核、中脑和延髓的离散区域。对穹窿下器官和新皮层中松弛素结合位点的表征显示,这两个区域均存在一类单一的高亲和力位点(解离常数Kd = 1.4 nM)。松弛素与两个脑室周器官(穹窿下器官和终板血管器)以及神经分泌性下丘脑大细胞神经核(即室旁核和视上核)的结合,为新出现的生理学证据提供了解剖学和生物化学基础,这些证据表明松弛素在血压控制和激素释放中起核心作用。我们得出结论,大鼠脑的离散区域中存在特异性、高亲和力的松弛素结合位点,其中一些位点的分布可能与松弛素在控制血管容量和血压方面的作用一致。