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Additive and/or Synergistic Action (Downregulation) of Androgens and Thyroid Hormones on the Cellular Distribution and Localization of a True Tissue Kallikrein, mK1, in the Mouse Submandibular Gland

Shingo Kurabuchi, Edward W. Gresik and Kazuo Hosoi

Department of Histology, Nippon Dental University School of Dentistry at Tokyo, Tokyo, Japan (SK); Department of Cell Biology and Anatomical Sciences, City University of New York Medical School, New York, New York (EWG); and Department of Molecular Oral Physiology, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan (KH)

Correspondence to: Shingo Kurabuchi, PhD, Dept. of Histology, Nippon Dental University School of Dentistry at Tokyo, Fujimi 1-9-20, Chiyoda-ku, Tokyo 102-8159, Japan. E-mail: kurabuchi{at}tokyo.ndu.ac.jp

We investigated the effects of 5-dihydrotestosterone (DHT), 3,5,3'-triiodo-L-thyronine (T₃), and dexamethasone (Dex) on the expression of mK1 in the granular convoluted tubule (GCT) cells of the submandibular gland (SMG) of hypophysectomized (Hypox) male mice by indirect enzyme-labeled antibody and immunogold antibody methods for light and electron microscopy. Hypox resulted in considerable atrophy of the GCT cells, which were always immunoreactive for mK1, and the cells were characterized by apical small dense secretory granules labeled with gold particles suggesting the presence of mK1, small Golgi apparatus, sparse rough endoplasmic reticulum (RER), and developed basal infoldings. Each of the hormones, DHT, T₃, and Dex, enhanced the GCT phenotype to various degrees in Hypox male mice. Both DHT alone and T₃ alone moderately inhibited mK1 synthesis by increasing the number of mK1-immunonegative GCT cells in Hypox males, but Dex alone had no inhibitory effect on mK1 synthesis. A significant trophic effect on GCT cells was induced by combined injection of DHT and T₃ or of all three hormones, and was reflected in the appearance of abundant large secretory granules, well-developed Golgi apparatus and RER, and reduced basal infoldings. Only a few such GCT cells were immunopositive for mK1, and the pattern of immunopositive and immunonegative cells very closely resembled the mosaic pattern seen in normal male GCTs. These findings suggested that the sexual dimorphism of mK1 expression and the morphological appearance of GCT cells can be induced by treatment with two hormones, DHT and T₃, but not by either of them alone. T₃ appears to have a permissive effect on committed GCT cells that results in downregulation of mK1 expression in these cells. (J Histochem Cytochem 52:1437–1446, 2004)

Key Words: mK1 • immunocytochemistry • submandibular gland • hypophysectomy • 5-dihydrotestosterone • 3,5,3'-triiodothyronine • dexamethasone • mouse

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