Hormonal Regulation of Fetal Brain Cell Proliferation: Presence in Serum of a Trophin Responsive to Pituitary Growth Hormone Stimulation

Abstract

Previous studies led to the hypothesis that brain growth was regulated by a growth hormone[GH]-dependent brain trophin. An in vitro bioassay system to assess this proposal was developed. Serum stimulated the uptake of tritiated thymidine into [rat] fetal brain cell DNA. This action could not be attributed to any nutrient contribulation but was due to a non-dialyzable, heat-stable serum growth factor. The levels of the growth factor in serum were reduced after pituitary removal. When added in physiological concentration, GH, prolactin, placental lactogen, insulin, nerve growth factor, thyroid and steroid hormones failed to simulate the action of serum or to act synergistically with a serum component to stimulate DNA synthesis. Thyroxine, estradiol-17.beta. and corticosterone inhibited serum activity. Administration of GH to hypophysectomized rats restored serum levels to normal demonstrating that the serum growth factor was a mediating trophin responsive to pituitary GH stimulation. The relationship of the brain trophin to other serum growth factors and its specificity of action remain to be defined. The present findings were in accordance with in vitro studies of hormonal influence on brain growth and support the proposal that fetal brain cell proliferation is stimulated by a serum trophin responsive to pituitary GH.