Specific Interaction of Nerve Growth Factor with Receptors in the Central and Peripheral Nervous Systems

Abstract

Nerve growth factor (NGF), a protein originally discovered as a diffusable substance produced by two mouse sarcomas (180 and 37)(28), stimulates marked neurite outgrowth by embryonic sympathetic and sensory ganglia both in vivo and in vitro. The latter phenomenon provided the basis for the bioassay (27). Antiserum to NGF blocks this effect, and if given to neonatal animals, produces a profound immunosympathectomy (26). Subsequent workers have noted wide-spread effects of NGF and its antisera on degeneration and regeneration of adrenergic fibers in both the central and peripheral nervous systems in embryonic and adult animals (3, 4). Its biological effects in the sensory nervous system, however, have been demonstrated only during a brief time span in chick embryonic development(27). To date no biological effects on the motor nervous system have been demonstrated. However, effects of the hormone on the development of neuroblastoma and pheochromocytoma cells in culture have been reported (22, 24, 31, 32, 39). In addition to the pronounced morphological changes, i.e. neurite production, several anabolic effects have been noted (7, 25, 27, 34). The sum of these findings suggests a hormone-like mode of action, pleiotypic in in character, that is important in regulating the development of peripheral neurons during embryonic development, and in some cases, in the mature animal.