No abstract

The concept that the salivary gland of the mouse is an endocrine organ for nerve growth factor (NGF) has been reexamined. Serum concentrations of the protein have been measured by radioimmunoassay in male and female mice and in mice from which the submandibular glands were removed. In spite of the fact that the submandibular glands of male mice contained more NGF than did those of female mice, no sex differences in circulating concentrations of the factor were detected. Furthermore, serum concentrations of NGF did not change after submandibular gland removal or after administration of several autonomic agonists. These results indicate that the submandibular glands are not endocrine organs with respect to NGF. On the other hand, extremely high concentrations of the factor are normally secreted in mouse saliva at levels that reflect the sex differences in the amount of NGF present in the glands. This finding suggests that the salivary gland is an exocrine organ for NGF and that the protein may play a biological role in saliva. For unknown reasons, nerve growth factor (NGF) is present in high concentrations in the submandibular glands of mice (1, 2) and in the venom of certain snakes (1, 3). The concentration of NGF is much higher in glands of male mice than in glands of female mice or prepubescent mice of either sex (1, 2). Biologically active NGF can also be detected in mouse blood (1). By using a sensitive radioimmunoassay, Hendry (2) found that the plasma of adult male mice contains 6 times as much NGF as does plasma of adult female mice, and Hendry and Iversen (4) found that sialoadenectomy caused a decrease in circulating levels of the factor. After submandibular gland removal, plasma concentrations of NGF dropped to 15% of control values over a period of 33 days and then returned to normal after an additional 27 days, at which time the sex difference in serum levels was reestablished (4). These findings have given rise to the widely held view that circulating levels of NGF are controlled (at least in part) by the submandibular glands (4,5 mouse serum has been found to be on the order of 10-30 min (5). Consequently, if the submandibular glands are a major source of circulating NGF, we would expect that removal of the glands would cause a rapid decrease in serum levels of the protein. However, Hendry and Iversen (4) found that this did not occur.In the present study, we reexamined the role that the submandibular glands might play in secreting NGF into the circulation. In contrast to the results of Hendry and Iversen (4), we found that removal of the submandibular glands has no effect on circulating levels of NGF over a period of 1-5 weeks after sialoadenectomy. Furthermore, serum levels of the factor in adult male and female mice were indistinguishable and did not reflect the sex differences found in salivary gland levels of the protein. Consequently, we conclude that the submandibular gland in the mouse does not function as an endocrine organ for NGF.These results then led to the idea that the salivar...

Normal primary chick embryo fibroblast cultures product a nerve growth-promoting factor which cross-reacts with monospecfic antibody to pure male mouse submaxillary gland nerve growth factor (NGF). When taken together with the earlier demonstration that mouse L2 CELLS AND 3T3 cells also produce an NGF-like protein, these findings suggest that secretion of this factor may be a general property of fibroblast.

5) Details of preparation and criteria of purity of these compounds will be reported in subsequent papers of this series.(6) Traube, Samml. chem. und chem.-techn. Vortr., 4, 255 (1 899). NHt CH2 COOH NH2CH2COOHVol. of groups, cc.7.7 16.1 18.9 42.7°Traube believed that a second hydroxyl group, or the second oxygen in a carboxyl group, occupied less space than the first.