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

Summarybetween 11 and 32 days of age. The known increase in mouse serum testosterone to adult male levels between 4-12 wk of age Using specific and sensitive radioimmunoassa~s for may be a factor in the late increase in NGF and EGF elevations growth factor (NGF) and epidermal growth factor (EGF), we after 32 days of age. studied the developmental profde 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 Nerve growth factor (NGF) and epidermal growth factor (EGF) cortex, and brain stem from ages 2-32 days. In addition, we are found in highest concentrations in the submaxillary gland assessed mouse serum thyroxine (T4) and triiodothyronine (T3) (SMG) of the adult male mouse (13,22). Both proteins are found levels in SePerate groups of animals ranging from 5-50 days of in peritubular cells (32,35) and are released concomitantly into age. Mean SMG EGF content and concentration exceeded that saliva (16,27). ~0 t h have C-terminus arginine residues (2, 13) and of NGF between 2 and 18 days of age. At all subsequent ages, exist in SMG as high molecular weight complexes with specific however, mean NGF and EGF content and concentration were arginine esteropeptidase subunits (34). In addition, both NGF, similar. SMG NGF and EGF content were low at 2 days of age, and EGF are found in higher concentrations in male than in decreased slightly through 8 days of age, and increased exponen-female glands. The concentration of both peptides in SMG is tially after 11 days of age with three phases of increase being increased by androgens (10, 17). Bynny et al. (9) described the apparent for both proteins. In the first phase, mean SMG NGF ontogenetic profile of radioimmunoassayable SMG EGF content and EGF contents increased 2.4 and 2.3-fold respectively between from 15 days ofage through adulthood. ~l~~ and ~~~i -~~~ 11 and 18 days of age. A second phase of increase was noted (3) have traced the developmental pattern of SMG NGF concenbetween 18 and 32 days when NGF and EGF increased 9g45-and trations after 20 days using an in vitro bioassay. Murphy et al. (26) 7805-fold respectively. In phase three (32-60 days of age) more have suggested that NGF and EGF are present in equal concenmodest increases of 6.5-fold in mean NGF and EGF content were trations in mature male mouse SMG; however, simultaneous noted.measurements of SMG NGF and EGF concentrations during Cerebellar NGF on cent rations hcreased from 681 to 2241 p d postnatal development in the mouse have not been conducted. mg protein between ages 2 and 15 days and subsequently feu aIn earlier reports we have described significant concentrations plateau level of 1304 pg/mg protein by age 18 days. Cerebral of radioimmunoassayble NGF in brain tissue of adult and develcortical NGF concentrations increased steadily from 251 to 1383 oping mice (37,40) but have not developed a complete ontogenetic p d m g protein between ages 2 and 32 days, w l~r e a s brain stem profile; moreover, we have...

Thyroxine Increases Submandibular Gland Nerve Growth Factor and Epidermal Growth Factor Concentrations Precociously in Neonatal Mice: Evidence for Thyroid Hormone-Mediated Growth Factor Synthesis

“…A further point of interest pertains to the observation of significant, albeit low concentrations of both NGF and EGF in the neonatal mouse SMG and is in agreement with previous observations (8,25), but not with those of other groups (9,13,26). The reason for this discrepancy is not clear, particularly since the sensitivities of the assay systems are similar.…”

“…SMG protease activity also is increased by T4 administration (7). Further, the ontogenetic profiles of SMG NGF and EGF concentrations correlate temporally with those of serum T4 and T3 (8).…”

“…NGF and EGF concentrations can be significantly modulated by androgens (3,4) and thyroid hormones (5-7) in the adult animal. In the neonatal mouse, the SMG is histologically and biochemically immature and contains very low concentrations of NGF and EGF (8). Thyroxine administration to neonatal mice accelerates histological and biochemical maturation of the SMG (7,(9)(10)(11)(12).…”

“…Aloe and Levi-Montalcini (13), and Gresik and Barka (9) have shown that thyroxine treatment of immature mice results in the appearance of measurable NGF and EGF, respectively, in the SMG as early as 15 days of age. In previous studies, we have shown that in normal intact neonatal mice, SMG NGF and EGF concentratio~is increase exponentially after 17-18 days of age (8) in agreement with previous reports (13,14), and the increases appear to correlate with increasing concentrations of T4 and T j (8). Since the time course of action of triiodothyronine requires a lag time of approximately 40 h prior to the appearance of newly accumulated EGF in the SMG of adult intact female mice (15), it became of interest to examine the effect of thyroxine on SMG NGF and EGF concentrations and the time of onset of thyroid hormone action in the neonatal mouse.…”

Urine and Kidney Epidermal Growth Factor: Ontogeny and Sex Difference in the Mouse

“…Since urine EGF increases in response to thyroxine (1 8) and endogenous thyroid hormone levels increase steeply between 5 and 15 days (20), the increasing endogenous thyroid hormone levels may be responsible for the massive increase in urine EGF between days 6 and 18. Exogenous growth hormone also increases urine EGF during the 1st wk of life (2 I), and since thyroid hormones are known to stimulate growth hormone secretion, growth hormone may contribute to this ontogenic urine EGF surge.…”