Ontogenesis of nerve growth factor and epidermal growth factor in submaxillary glands and nerve growth factor in brains of immature male mice: correlation with ontogenesis of serum levels of thyroid hormones.

Abstract

Summary: Using specific and sensitive radioimmunoassays for nerve growth factor (NGF) and epidermal growth factor (EGF), we studied the developmental profile of NGF and EGF concentrations in male mouse submaxillary gland (SMG) from 2–60 days of age. We measured NGF concentrations in mouse cerebellum, cerebral cortex, and brain stem from ages 2–32 days. In addition, we assessed mouse serum thyroxine (T4) and triiodothyronine (T3) levels in seperate groups of animals ranging from 5–50 days of age. Mean SMG EGF content and concentration exceeded that of NGF between 2 and 18 days of age. At all subsequent ages, however, mean NGF and EGF content and concentration were similar. SMG NGF and EGF content were low at 2 days of age, decreased slightly through 8 days of age, and increased exponentially after 11 days of age with three phases of increase being apparent for both proteins. In the first phase, mean SMG NGF and EGF contents increased 2.4− and 2.3-fold respectively between 11 and 18 days of age. A second phase of increase was noted between 18 and 32 days when NGF and EGF increased 9845− and 7805-fold respectively. In phase three (32–60 days of age) more modest increases of 6.5-fold in mean NGF and EGF content were noted.Cerebellar NGF concentrations increased from 681 to 2241 pg/mg protein between ages 2 and 15 days and subsequently fell to a plateau level of 1304 pg/mg protein by age 18 days. Cerebral cortical NGF concentrations increased steadily from 251 to 1383 pg/mg protein between ages 2 and 32 days, whereas brain stem NGF concentrations maintained a plateau averaging 1100 pg/mg protein.Serum T4 concentrations in the mouse increased dramatically from 2.5 μg/dl at 5 days to a maximum of 8.1 μ/dl at 15 days, thereafter decreasing to a nadir 4.4 μ/dl by 40 days. Serum T3 concentrations followed a similar pattern, rising from 25 ng/dl on postnatal day 5 to 93 ng/dl on day 15, with a subsequent decline to 63 ng/dl by day 30. These results indicate a correlation between the increase in serum thyroid hormone levels in the mouse and the increases in SMG NGF and EGF levels and brain NGF levels between 5 and 32 days.Speculation: We and others have demonstrated that thyroid hormones increase brain NGF concentrations and stimulate submaxillary gland NGF and EGF synthesis. The present results are compatible with the hypothesis that the early increase in circulating thyroid hormone concentrations in the mouse play an important role in the increase in cerebral and cerebellar NGF levels during the first 3 wk and the increase in SMG NGF and EGF concentrations between 11 and 32 days of age. The known increase in mouse serum testosterone to adult male levels between 4–12 wk of age may be a factor in the late increase in NGF and EGF elevations after 32 days of age.