Influence of Androgens on Gene Expression in the BALB/c Mouse Submandibular Gland

Abstract

Androgens have profound effects on the murine submandibular gland. Our objective was to determine the nature and extent of androgen control of gene expression in the submandibular gland, and to explore the degree to which this might account for known sex differences. Orchiectomized male BALB/c mice were treated with placebo- or testosterone-containing hormone pellets for 14 days. Glands were collected, and total RNA was isolated. Samples were analyzed for differentially expressed mRNAs by CodeLink microarrays, and the data were evaluated with GeneSifter. Androgens significantly (p < 0.05) influenced the expression of over 1300 genes, and many (n = 366) of the genes differentially regulated by androgen treatment were also differentially expressed in males compared with the females in our previous study. These findings support our hypotheses that testosterone extensively influences gene expression in the male submandibular gland, and that many of the sex differences are due to androgens.

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References

Ariga H, Edwards J, Sullivan DA -1989-. Androgen control of autoimmune expression in lacrimal glands of MRL/Mp-lpr/lpr mice. Clin Immunol Immunopathol 53:499–508.

Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, et al. -2000-. Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat Genet 25:25–29.

Bjorling DE, Beckman M, Clayton MK, Wang ZY -2002-. Modulation of nerve growth factor in peripheral organs by estrogen and progesterone. Neuroscience 110:155–167.

Cangussu SD, Vieira FG, Rossoni RB -2002-. Sexual dimorphism and seasonal variation in submandibular gland histology of Bolomys lasiurus -rodentia, muridae-. J Morphol 254:320–327.

Cerbon MA, Camacho-Arroyo I, Gamboa-Dominguez A, Gonzalez-Mariscal G -1996-. The rabbit submandibular gland: sexual dimorphism, effects of gonadectomy, and variations across the female reproductive cycle. J Comp Physiol [A] 178:351–357.

Desai KV, Kondaiah P -2000-. Androgen ablation results in differential regulation of transforming growth factor-beta isoforms in rat male accessory sex organs and epididymis. J Mol Endocrinol 24:253–260.

Hosoi K, Kobayashi S, Ueha T -1978-. Influence of androgens on beta-glucuronidase activity in liver, kidney and submandibular salivary gland of the mouse. Arch Oral Biol 23:905–909.

Hosoi K, Tanaka I, Murai T, Ueha T -1984-. Inhibitory effect of androgen on the synthesis of proteinase F in the male mouse submandibular gland. J Endocrinol 100:253–262.

Jayasinghe NR, Cope GH, Jacob S -1990-. Morphometric studies on the development and sexual dimorphism of the submandibular gland of the mouse. J Anat 172:115–127.

10.

Kim YK, Ogita Z -1981-. Sexual dimorphism of SDS peptide patterns from the submaxillary glands of mice. J Exp Zool 218:447–453.

11.

Koski H, Konttinen YT, Hietanen J, Tervo T, Malmström M -1997-. Epidermal growth factor, transforming growth factor-alpha, and epidermal growth factor receptor in labial salivary glands in Sjögren’s syndrome. J Rheumatol 24:1930–1935.

12.

Kurihara K, Maruyama S, Sakagami H, Ueha T -1999-. Differences in androgen-dependent induction of mk1, true tissue kallikrein in C3H/HeN and ICR mouse submandibular gland. Horm Metab Res 31:370–374.

13.

Kyakumoto S, Kurokawa R, Ohara-Nemoto Y, Ota M -1986-. Sex difference in the cytosolic and nuclear distribution of androgen receptor in mouse submandibular gland. J Endocrinol 108:267–273.

14.

Laine M, Blauer M, Ylikomi T, Tuohimaa P, Aitasalo K, Happonen RP, et al. -1993-. Immunohistochemical demonstration of androgen receptors in human salivary glands. Arch Oral Biol 38:299–302.

15.

Lee HJ, Chang C -2003-. Recent advances in androgen receptor action. Cell Mol Life Sci 60:1613–1622.

16.

Martel C, Rheaume E, Takahashi M, Trudel C, Couet J, Luu-The V, et al. -1992-. Distribution of 17 beta-hydroxysteroid dehydrogenase gene expression and activity in rat and human tissues. J Steroid Biochem Mol Biol 41:597–603.

17.

Mizuki N, Kasahara M -1992-. Mouse submandibular glands express an androgen-regulated transcript encoding an acidic epididymal glycoprotein-like molecule. Mol Cell Endocrinol 89:25–32.

18.

Mong JA, Devidze N, Frail DE, O’Connor LT, Samuel M, Choleris E, et al. -2003-. Estradiol differentially regulates lipocalin-type prostaglandin D synthase transcript levels in the rodent brain: evidence from high-density oligonucleotide arrays and in situ hybridization. Proc Natl Acad Sci USA 100:318–323.

19.

Morrell JI, Gresik EW, Barka T -1987-. Autoradiographic localization of dihydrotestosterone binding in the major salivary glands and other androgen-responsive organs of the mouse. J Histochem Cytochem 35:1053–1058.

20.

Ogawa N, Dang H, Lazaridis K, McGuff HS, Aufdemorte TB, Talal N -1995-. Analysis of transforming growth factor beta and other cytokines in autoimmune exocrinopathy -Sjögren’s syndrome-. J Interferon Cytokine Res 15:759–767.

21.

Pascall JC, Saunders J, Blakeley DM, Laurie MS, Brown KD -1989-. Tissue-specific effects of castration and ovariectomy on murine epidermal growth factor and its mRNA. J Endocrinol 121:501–506.

22.

Sawada K, Noumura T -1991-. Effects of castration and sex steroids on sexually dimorphic development of the mouse submandibular gland. Acta Anat -Basel- 140:97–103.

23.

Sheflin LG, Zhang W, Spaulding SW -2001-. Androgen regulates the level and subcellular distribution of the AU-rich ribonucleic acid-binding protein HuR both in vitro and in vivo. Endocrinology 142:2361–2368.

24.

Siminoski K, Bernanke J, Murphy RA -1993-. Nerve growth factor and epidermal growth factor in mouse submandibular glands: identical diurnal changes and rates of secretagogue-induced synthesis. Endocrinology 132:2031–2037.

25.

Sims-Sampson G, Gresik EW, Barka T -1984-. Histochemical localization of ouabain-sensitive, K+-dependent p-nitrophenylphosphatase -Na+-K+-ATPase- activity in the submandibular gland of the mouse: effect of androgen, thyroid hormone, or postnatal age. Anat Rec 210:53–60.

26.

Song WC -2001-. Biochemistry and reproductive endocrinology of estrogen sulfotransferase. Ann NY Acad Sci 948:43–50.

27.

Sordello S, Bertrand N, Plouet J -1998-. Vascular endothelial growth factor is up-regulated in vitro and in vivo by androgens. Biochem Biophys Res Commun 251:287–290.

28.

Sullivan DA -1997-. Sex hormones and Sjögren’s syndrome. J Rheumatol 24-Suppl 50-:17–32.

29.

Sullivan DA, Edwards JA -1997-. Androgen stimulation of lacrimal gland function in mouse models of Sjögren’s syndrome. J Steroid Biochem Mol Biol 60:237–245.

30.

Treister NS, Richards SM, Lombardi MJ, Rowley P, Jensen RV, Sullivan DA -2005-. Sex-related differences in gene expression in salivary glands of BALB/c mice. J Dent Res 84:160–165.

31.

Tuomela T, Miettinen P, Pesonen K, Viinikka L, Perheentupa J -1990-. Epidermal growth factor in mice: effects of estradiol, testosterone and dexamethasone. Acta Endocrinol -Copenh- 123:211–217.

32.

Whitacre CC -2001-. Sex differences in autoimmune disease. Nat Immunol 2:777–780.

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