Estrogen deficiency and colonic function: surgical menopause and sex differences in angiotensin and dopamine receptor interaction.

Garrido-Gil, Pablo; Rodriguez-Perez, Ana I; Lage, Lucia; Labandeira-Garcia, Jose Luis

The physiopathological mechanisms that regulate menopausal and sex differences in colonic transit, inflammatory processes and efficacy of treatments have not been clarified. The dopaminergic and renin-angiotensin systems (RAS) coexist in the gut and regulate different processes such as motility, absorption/secretion and inflammation. We investigated the changes in expression of major angiotensin and dopamine receptors in the colon of male, female and ovariectomized female mice. Possible interaction between both systems was investigated using male and female mice deficient (ko) for major angiotensin and dopamine receptors. In wild type mice, colonic tissue from females showed lower angiotensin type 1 (AT1)/angiotensin type 2 (AT2) ratio (an index of proinflammatory/anti-inflammatory RAS balance), lower dopamine D1 and D2 receptor expression, and lower levels of proinflammatory and pro-oxidative markers relative to males. Interestingly, ovariectomy increased the expression of pro-inflammatory AT1 receptor expression and decreased anti-inflammatory AT2 receptor expression, increased D1 and D2 receptor expression, and increased the levels of proinflammatory and pro-oxidative markers. Ovariectomy-induced changes were blocked by estrogen replacement. The present results suggest a mutual regulation between colonic angiotensin and dopamine receptors, and sex differences in this mutual regulation. Estrogen regulates changes in both angiotensin and dopamine receptor expression, which may be involved in sex- and surgical menopause-related effects on gut motility, permeability and vulnerability to inflammatory processes.