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

Neurogastroenterol Motil. 2012 Apr;24(4):392-e174. doi: 10.1111/j.1365-2982.2011.01875.x. Epub 2012 Jan 27.

Abstract

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.

Aims: 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.

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

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Colon / drug effects
  • Colon / physiology*
  • Defecation / drug effects
  • Defecation / physiology*
  • Diarrhea / metabolism*
  • Enzyme-Linked Immunosorbent Assay
  • Fluoxetine / pharmacology
  • Gastrointestinal Motility / drug effects
  • Gastrointestinal Motility / physiology*
  • Male
  • Mice
  • Mice, Knockout
  • Muscle Contraction / drug effects
  • Muscle Contraction / physiology
  • Progesterone / metabolism*
  • Progesterone / pharmacology
  • Receptors, Progesterone / metabolism
  • Serotonin / metabolism
  • Serotonin Uptake Inhibitors / pharmacology

Substances

  • Receptors, Progesterone
  • Serotonin Uptake Inhibitors
  • Fluoxetine
  • Serotonin
  • Progesterone