Novel female sex-dependent actions of oestrogen in the intestine

Abstract

The intestine is an oestrogen responsive organ and circulatory oestrogens suppress Cl − secretion across the epithelium of the colon to promote fluid retention at the luteal stage of the menstrual cycle. Ion transporters in the colon which are involved in Cl − secretion show differential expression between males and females as do the signalling protein kinase intermediates involved in acutely regulating these transporters. Work from our laboratory has identified the KCNQ1/KCNE3 channel as one of the principal targets for oestrogen-induced signalling cascades in the distal colon. Through inhibition of the KCNQ1 channel, basolateral K + recycling is decreased so reducing the favourable electrochemical gradient for Cl − extrusion at the apical membrane. The actions of oestrogen on non-reproductive tissues such as the colon, kidney, lung and sweat gland will affect whole body electrolyte and fluid homeostasis and also have consequences for reproductive potential.

17β-Estradiol Inhibits IL-8 in Cystic Fibrosis by Up-Regulating Secretory Leucoprotease Inhibitor

“…n 5 4. b versa (52)(53)(54). Cell signaling responses initiated in the rapid phase of estrogen action additionally have been found to persist over hours to days and therefore are not purely nongenomic and in vivo are unlikely to be epiphenomena to the traditional genomic response (55).…”

Estrogen inhibits chloride secretion caused by cholera and Escherichia coli enterotoxins in female rat distal colon

“…Moreover, estrogen enhances amiloride-sensitive Na + absorption in mouse renal cortical collecting duct and distal colon (Robles, Flores, Thomas and Harvey, unpublished data). Therefore, we conclude that the ability of 17-estradiol to limit secretion and enhance absorption in the major organs regulating whole body fluid and electrolyte balance [51] may contribute in the well-known fluid retentive properties of this hormone.…”

“…This suggests 17-estradiol may also alter colonic ion transport during high estrogen states such as pregnancy and certain phases of the menstrual cycle [48,50], and during use of oral contraceptives [49] and estrogen treatment [50,51]. A molecular target of the anti-secretory effects of estrogen has been identified as the basolateral KCNQ1 K + channel in rat colon [52].…”

Novel aspects of oestrogen actions

“…The reviews by Angel Nadal (Nadal et al . 2009) and Fiona O’Mahony (O’Mahony et al . 2009) give good examples of ‘priming’ interactions between rapid and latent phases of E2 actions in the pancreatic β‐cell and distal colon, respectively.…”

“…Oestrogen has a stimulatory action on glucose‐induced insulin secretion and on pancreatic β‐cell survival which may have important protective effects in pregnancy to guard against gestational diabetes. The novel aspect of sexual dimorphism of oestrogen action on epithelial ion transporter activity and protein expression is reviewed by O’Mahony et al . (2009).…”