Effect of progesterone on colonic motility and fecal output in mice with diarrhea.

BACKGROUND

Patients with diarrhea and slow transit constipation (STC) have high 5-HT levels. In STC, the high 5-HT levels have been difficult to explain, as 5-HT stimulates peristalsis. Over expression of progesterone (P4) receptors in epithelial and muscle cells of the colon may reconcile this contradiction because P4 decreases SERT and increases 5-HT levels, but their effects are rendered ineffective because of the impaired muscle contraction.

OBJECTIVE

We examined whether P4 treatment could reduce the stool output in two mouse diarrheal models because of higher 5-HT levels, the SERT knock-out (KO), and the fluoxetine-treated mice.

METHODS

Contractility of colon circular muscle strips from wild mice was studied. Fecal water and dry fecal output were measured daily over a 4-day period in wild and SERT-KO mice and in fluoxetine-treated mice treated with IM saline or P4. 5-HT levels were measured using ELISA.

RESULTS

Progesterone blocked the spontaneous and stimulated phasic contractions. Fecal water output measured in two consecutive 4-day periods was not different in wild and SERT-KO mice. The fecal output in the SERT-KO mice was higher than in wild mice. P4 treatment reduced the 4-day fecal output in both groups compared with saline treatment. Oral fluoxetine treatment increased 5-HT levels in wild mice and increased the 4-day fecal output compared with oral saline. P4 treatment caused a decrease in the fecal output in both groups.

CONCLUSIONS

Progesterone decreased the contractility of circular muscle strips, and reduced the fecal output in two diarrheal models, the SERT-KO and fluoxetine-treated mice.