Morphologic changes in the granular convoluted tubule cells of the mouse submandibular gland following hypophysectomy and hormonal replacement

Abstract

Morphological changes in the granular convoluted tubule (GCT) cells of the male mouse submandibular gland (SMG) were examined following hypophysectomy and hormonal replacement. Semithin sections stained with Heidenhain's iron hematoxylin showed that hypophysectomy severely regressed the GCT phenotype. Although only a few dispersed cells containing secretory granules were observed in the GCT segments under a light microscope, electron microscopy revealed that many regressed cells continued to constitutively elaborate apical secretory granules (although they were very small) and contained a euchromatic nucleus at the center of the cell, poor rough endoplasmic reticulum (RER) and Golgi apparatus in the perinuclear region, and well-developed basal infoldings. These findings suggest that hypophysectomy resulted in atrophy of GCT cells, but that they retained evidence of being secretory cells. 5 alpha-Dihydrotestosterone (DHT); 3,5,3'-triiodo- l-thyronine (T(3)); and dexamethasone (Dex) each enhanced the GCT phenotype of hypophysectomized males to some degree. Combined hormonal replacement with DHT + T(3) in hypophysectomized males restored a nearly normal male GCT phenotype with a full complement of secretory granules and rare basal infoldings, whereas T(3) alone induced a normal female-like GCT phenotype, with considerably abundant secretory granules and the usual short basal infoldings, in hypophysectomized male glands. Furthermore, Dex was found to synergistically enlarge secretory granules when administered with T(3) and/or DHT, although it was only weakly effective in enhancing the GCT phenotype when used alone. Taken together, the above findings confirmed that the GCT phenotype of the mouse SMG is regulated by the synergistic action of pituitary-dependent hormones.

Hypophysectomy and hormonal therapy modulate mK1-immunoreactive duct cells in the mice sublingual glands

“…We confirmed that essentially all of the immature GCT cells in the glands of prepubertal mice stained positive for mK1, whereas after the onset of puberty, many of the cells differentiated into full-fledged granular cells and became negative for mK1 . We also confirmed that all the atrophied GCT cells following hypophysectomy were mK1-positive, whereas, many of the GCT cells that developed a granular cell phenotype after hormone replacement therapy (Kurabuchi 2002) became mK1-negative . Taken together, these findings suggest that mK1 is a marker of granular duct cells with a poor granular cell phenotype.…”

“…The animals were housed under controlled environmental conditions (22°C, LD 12 h:12 h), and provided with food and water ad libitum. At 12 weeks of age, the hypophysectomized mice were divided into eight groups, each group consisting of at least five animals, and injected with hormones as described in our previous papers (Kurabuchi 2002(Kurabuchi , 2006Kurabuchi et al 2002. In brief, the doses (per kg body weight) per injection of the hormones were as follows: 5a-dihydrotestosterone (DHT: Wako Ltd., Osaka, Japan), 20 mg; dexamethasone (Dex: Wako Ltd., Osaka, Japan), 10 mg; 3,5,3 0 -triiodo-L thyronine (T 3 : ICN Biochem, Aurora, Ohio, USA), 1 mg.…”

Thyroid hormone regulation of granular intercalated duct cells in the submandibular glands of female mice

“…8,16 Briefly, small pieces of the fixed SMGs, as described above, were dehydrated in a graded series of ethanol solutions and embedded in epoxy resin. Deresined 1-µm-thick sections were stained with Heidenhain's iron hematoxylin for the lightmicroscopy examination.…”

“…Our group's previous studies using adult male mice suggest that T 3 alone induces a normal female-like GCT phenotype in the glands of Hypox males. 8,14,15 However, because the disappearance of the GID cells after puberty was irreversible, the effects of thyroid hormones on GID cells in adult male glands could not be elucidated. To define the role of thyroid hormones in the morphological aspects of GID cells, the present experimental series examined the effects of thyroid hormones on the SMGs of female mice.…”

“…Hypophysectomy (Hypox) or castration and hormonal replacement during adulthood does not cause GID cells to reappear in the ID segments of male glands. [8][9][10] However, GID cells have been identified in the IDs of glands in androgen-insensitive (Tfm/Y) male mice. 11 Interestingly, the disappearance of GID cells in males parallels the development of Leydig tissue 12 and blood androgen levels.…”