Androgens suppress the sialyltransferases ST3GAL1 and ST3GAL4 and modulate mucin 10 glycosylation in the submandibular gland, related to sex differences in commensal microbiota composition in mice

Mana Deminami; Miku Hashimoto; Hiroki Takahashi; Naoki Harada; Yukari Minami; Tomoya Kitakaze; Wataru Masuda; Shigeo Takenaka; Hiroshi Inui; Ryoichi Yamaji

doi:10.1093/bbb/zbae175

Androgens suppress the sialyltransferases ST3GAL1 and ST3GAL4 and modulate mucin 10 glycosylation in the submandibular gland, related to sex differences in commensal microbiota composition in mice

Biosci Biotechnol Biochem. 2024 Nov 21:zbae175. doi: 10.1093/bbb/zbae175. Online ahead of print.

Authors

Mana Deminami¹, Miku Hashimoto¹, Hiroki Takahashi², Naoki Harada^{1

2}, Yukari Minami¹, Tomoya Kitakaze^{1

2}, Wataru Masuda³, Shigeo Takenaka⁴, Hiroshi Inui^{1

2

5}, Ryoichi Yamaji^{1

2

6}

Affiliations

¹ Division of Applied Life Sciences, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Sakai, Osaka, Japan.
² Department of Applied Biological Chemistry, Graduate School of Agriculture, Osaka Metropolitan University, Sakai, Osaka, Japan.
³ Department of Nutrition, Faculty of Home Economics, Kyushu Women's University, Kitakyushu, Fukuoka, Japan.
⁴ Division of Nutrition, Graduate School of Human Life and Ecology, Osaka Metropolitan University, Habikino, Osaka, Japan.
⁵ Department of Health and Nutrition, Otemae University, Osaka, Japan.
⁶ Center for Research and Development of Bioresources, Osaka Metropolitan University, Sakai, Osaka, Japan.

PMID: 39572079
DOI: 10.1093/bbb/zbae175

Abstract

Sex differences exist in the commensal microbiota that impact on multiple physiological processes in the host. Here, we examined the mechanism by which the sex differences are formed. In addition to the epithelial ductal cell, the acinar cell mass in the submandibular gland was associated with androgen-androgen receptor (AR) signaling. There was a sex difference in the formation of submandibular mucin 10 (MUC10) in SDS-PAGE. Neuraminidase treatment, which hydrolyzes terminal sialic acid, influenced the mobility shift of MUC10. Androgen-AR signaling negatively regulated St3 β-galactoside α-2,3-sialyltransferase 1 (St3gal1) and St3gal4 in the submandibular gland. There was a trend and significant sex differences in α-diversity (Shannon, p=0.09) and β-diversity (unweighted UniFrac) in oral microbiota composition, respectively. Some female-preferring bacteria including Akkermansia muciniphila can assimilate mucin by degrading terminal sialic acids. Our results indicate that androgen-AR signaling suppresses ST3GAL1 and ST3GAL4, which can influence sex differences in commensal microbiota composition.

Keywords: mucin 7 (MUC7) ortholog; oral microbiota; saliva; sex difference; testosterone.