Estrogen Regulates Duodenal Calcium Absorption Through Differential Role of Estrogen Receptor on Calcium Transport Proteins

Dig Dis Sci. 2020 Dec;65(12):3502-3513. doi: 10.1007/s10620-020-06076-x. Epub 2020 Jan 23.

Abstract

Background and aims: Intestinal calcium absorption from the diet plays important role in maintaining calcium homeostasis in the body. Estrogen exerts wide physiological and pathological effects in the human. Previous studies have shown that estrogen is involved in the intestinal calcium absorption. In this study, we made investigation on the mechanism of estrogen action on duodenal calcium absorption.

Methods: The experiments were performed in mice, human, and human duodenal epithelial cells, SCBN cells. Murine duodenal calcium absorption was measured by using single pass perfusion of the duodenum in vivo. The calcium absorption of SCBN cells was evaluated by calcium imaging system. The expression of calcium transport proteins, transient receptor potential cation channel (TRPV6) and plasma membrane calcium pump (PMCA1b), in the duodenum or SCBN cells were analyzed by western blot.

Results: The duodenal calcium absorption in ovariectomized mice was significantly decreased, compared with control female mice, which returned to control level after 17β-estradiol replacement treatment. Estrogen regulated the expressions of TRPV6 and PMCA1b in murine and human duodenal mucosae and SCBN cells. The further results from SCBN cells showed that 17β-estradiol regulated calcium influx through the respective effects of estrogen receptor (ER) ɑ and β on TRPV6 and PMCA1b.

Conclusion: Estrogen regulates duodenal calcium absorption through differential role of ERɑ and ERβ on duodenal epithelial cellular TRPV6 and PMCA1b. The study further elucidates the mechanism of estrogen on the regulation of intestinal calcium absorption.

Keywords: Calcium absorption; Calcium transport proteins; Duodenum; Estrogen; Estrogen receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Transport, Active / drug effects
  • Biological Transport, Active / physiology
  • Calcium / metabolism*
  • Calcium Channels / metabolism*
  • Cells, Cultured
  • Duodenum / physiology*
  • Estradiol / pharmacokinetics*
  • Estrogens / pharmacokinetics
  • Humans
  • Intestinal Absorption / drug effects
  • Intestinal Absorption / physiology
  • Intestinal Mucosa / metabolism*
  • Mice
  • Plasma Membrane Calcium-Transporting ATPases / metabolism*
  • Receptors, Estrogen / metabolism*
  • TRPV Cation Channels / metabolism*

Substances

  • ATP2B1 protein, human
  • Calcium Channels
  • Estrogens
  • Receptors, Estrogen
  • TRPV Cation Channels
  • TRPV6 protein, human
  • Trpv6 protein, mouse
  • Estradiol
  • Plasma Membrane Calcium-Transporting ATPases
  • Atp2b1 protein, mouse
  • Calcium