Role of thyroid hormone in the initiation of EGF (epidermal growth factor) expression in the sublingual gland of the postnatal mouse

Abstract

The effect of triiodo-L-thyronine (T 3 ) and propylthiouracil (PTU) on the initiation of epidermal growth factor (EGF) expression in the sublingual glands (SLGs) of postnatal mice was investigated by indirect enzyme-labeled and immunogold antibody methods for light and electron microscopy, respectively. In normal males, EGF immunoreactivity first appeared in a few scattered granular cells of striated ducts (SDs) at 5 weeks of age, and the immunoreactive cells had increased in number at 6 weeks of age. No EGF expression was observed in the glands of females at any ages examined. When T 3 (1 mg/kg body weight) was given to males every other day for 2 weeks before examination, EGF expression began earlier; the immunoreactive granular cells were first detected at 4 weeks of age, and at later ages they were markedly increased in number compared to those of normal males. Moreover, T 3 was capable of inducing EGF in the female glands. After T 3 was administered to females in the same manner as in males, a few immunoreactive cells were first detected at 5 weeks of age, and increased numbers were detected at later ages. By contrast, when PTU (1 mg/kg body weight) was given to male mice every other day for 2 weeks before examination, the EGF-immunoreactive cells were markedly decreased in number compared to those of normal males of the same age. Electron microscopy revealed that many SD cells contained secretory granules, and that these cells constituted the granular striated tubule (GST) in a portion of SDs, but they were undetectable by light microscopy, because their secretory granules were minimal in size and few in number. Gold-labeling of EGF was confined to the secretory granules of scattered granular cells, whose secretory granules were far larger in size and more abundant than those of the GST cells. These results suggest that thyroid hormone is essential to differentiation of the cellular phenotype of GST precursor cells into typical granular cells (detectable by light microscopy) that express EGF in the mouse SLG, showing a close resemblance to the submandibular granular convoluted tubule cells.

Repeated androgen and thyroid hormone injection modulates the morphology of hormone-responsive duct cells in the mouse parotid gland

“…[2][3][4] In the SLGs of intact mice, a few scattered GCT-like granular cells are known to occur frequently in the striated ducts of adult males, but not females. 1,6,11 Even after long exposure to high levels of DHT and/or T 3 , in the same way as in this study, a few GCT-like granular cells were always induced in the SLGs of females. 1,6 However, the present study showed that such granular cells were rarely induced in the parotid glands of hormoneinjected female mice.…”

“…1,7,11,17 Using normal female 1 and hypophysectomized male 7 mice SLGs, our previous study established that combinations of thyroid hormones and androgens converted a few GST cells to GCT-like fully fledged granular cells. The same conversion occurred in a few GST cells in the parotid gland in response to external hormones.…”

“…These findings suggest that nearly all GST-like immature cells develop into fully fledged granular cells and contribute GCTs in the SMGs, and that only a few GST cells in the SLGs of males, but not females, are converted into GCT-like cells. 7,11 Normally all GST cells in the SLGs of females and the parotid glands of both sexes retain the immature form of granular cells, even in adulthood.…”

“…The same variation in the response to hormones was also detected in SLG GST cells. 7,11 In the mouse SMG, it is known that the expression of androgen receptors varies with the GCT cells, 29,30 and is induced by thyroid hormone 25,26 and androgen itself. 27 Our previous studies suggested that such variation of androgen receptors (and probably other hormone receptors, such as thyroid hormone receptors) in GCT cells would cause cellular mosaic expression of some GCT-specific secretory products.…”

“…1,6 Such GCT-like cells were hormonally induced in the female gland GST segments. 1,6 These GCT-like cells immunostained positive for GCTspecific secretory products, epidermal growth factor (EGF), nerve growth factor (NGF), renin, and proteinase A (mK22, one of the mouse kallikrein gene family members), [6][7][8][9][10][11] whereas the GST cells of both sexes immunostained positive only for a true tissue kallikrein, mK1. 7 Because mK1 is thought to be a neonatal-type secretory product in the SMG, [12][13][14] the author suspects that many GST cells retain the immature type and only a few are hormonally converted to the fully fledged granular type, GCT-like cells.…”