Genistein Stimulates Jejunal Chloride Secretion via Sex-dependent, Estrogen Receptor or Adenylate Cyclase Mechanisms

Cellular Physiology and Biochemistry

Layla Al-Nakkash¹ 

关键词: Genistein;    Estrogen receptors;    Estradiol;    Adenylate cyclase;    Chloride secretion;    Jejunum;    Signaling pathways;    Intestine;   

DOI  :  10.1159/000339053

学科分类：分子生物学，细胞生物学和基因

来源: S Karger AG

【 摘 要 】

Background/Aims Daily subcutaneous injections with the phytoestrogen genistein, 600 mg/ kg genistein/day (600G) significantly increased intestinal chloride (Cl^-) secretion (I_sc, µA/cm²) in C57BL/6J female and male murine jejunum after 1-2-weeks treatment. Methods and Results In 600G females, basolateral application of the adenylate cyclase inhibitor MDL-12330A (10 µM) significantly reduced basal and total I_sc in the presence of forskolin (27 and 40% respectively, P < 0.05), with no effect in 600G males, suggesting that 600G-mediated increases in I_sc in females are due to an adenylate cyclase-dependent mechanism. Concomitant injections with the non-selective estrogen receptor (ER) antagonist ICI-182780 (25 mg/kg/day) resulted in a significant inhibition of basal I_sc in males (38%, P < 0.05), but was without effect in females (further reinforcing an ER-independent mechanism of action). The ERα-selective antagonist (MPP, 25 mg/kg/day) similarly significantly inhibited the basal I_sc (37%, P < 0.05) in males, whereas the ERβ-selective antagonist (PHTPP, 25 mg/kg/day) was without effect, suggesting that 600G-mediated increases in I _sc in male mice are due to an ERα-dependent mechanism. Jejunum ERα/actin expression was significantly increased by 600G in males. Compared to intact mice, orchiectomy has differing effects on 600G-mediated basal Isc; castration (CAST) abolished the 600G-mediated increases in I _sc, and ovariectomy (OVX) had no effect on the 600G-stimulated increases in I _sc. Daily estradiol injections (10-20 mg/kg body weight estradiol (10E2 or 20E2) had no effect in intact females, whereas 10E2 significantly increased basal I_sc in OVX females. Conclusion These data suggest that daily estradiol and genistein injections have differential sex-dependent mechanisms of action on murine intestinal Cl^- secretion.

【 授权许可】

CC BY-NC-ND