A new study suggests that estrogen fine-tunes gut cell communication to increase serotonin-powered pain.

Study: A cellular base for increased intestinal sensitivity in womenImage Credit: Prathankarnpap / Shutterstock

*Important Information: Biorxiv Publishes preliminary scientific reports that are not reviewed by colleagues and therefore, it should be considered as decisive, guide clinical practice/health related behavior, or established information.

Posted in a recent study Biorxiv The preprint* server identified a new estrogen-respondent passage, with two types of anterondocrine cells (EEC) communicate to increase intestinal sensitivity in women.

Chronic gastrointestinal (GI) pain is more common in women, which can increase with changes in estrogen levels during pregnancy and menstrual cycle. While the relevant estrogen targets remain unknown, intestine can be a possible site of mucosa action, where sensory nerve fiber interacts with epithelial cells. Most epithelial cells that lining the intestines are enterocytes, which mainly serve to absorb electrolytes, nutrients and water from the digestive system.

Rare, stimulants are contradictory between EEC enterocytes and detect luminal content and release neurotransmitters and peptides, triggering physical reactions. Serotonergic enterochromephin (EC) cells are a subtype of EEC cells that activate mucosal spinal affrants to induce intestinal pain. This EC cell-sensory nerve circuit displays an increase in sensitivity in female mice, suggests that it can be a place for the increase of intestinal pain.

L-cell, another EEC subtype, is known for its role in secreting hormones, such as peptide yy (PYY) and GlucagonSuch as peptide -1 (GLP -1), and sensing postprands. The exit administration of Cleived Pyy3-36 peptide causes gastrointestinal discomfort. Pyy3-36 selectively binds neuropeptide Y2 receptors (NPY2Rs) in the brain and vagina.

The larger Pyy1-36 peptide also activates NPY1R, which is expressed in the intestine by spinal eporters and EC cells. With the primary detector of toxic stimuli with intestinal epithelium with EC cells, coupling between NPY1R and Pyy1-36 can possibly cause hypersensitivity and discomfort of the intestine. However, some studies have examined their consequences on parasin coupling and intestinal pain between EC and L cells.

Study and conclusions

The current study showed that crossstocks between EC and L cells resulted in hypersensitivity to the intestine. First, the team investigated whether the integration is included in the difference sensitivity of the mucosal sensory affair, which has been shown to display high basic activity in female mice earlier than male mice. To end this, the aurable nerve fiber activity in former Vivo mucosal preparation (EVMAR) was compared between male and ovariectomized (OVX) or intact female mice.

Higher reactions were recorded in women compared to men, and this difference was seen in OVX women. In addition, estrogen had a notable effect on behavioral measures of intestinal sensitivity, which was determined by evaluating motor reactions of the intestine for colorectal dispenses. Reactions in women were largely observed when OVX eliminated estrogen. In particular, a single treatment of OVX women with Estradiol benzoate (EB) reversed this ternity.

In addition, the team noticed that the estrogen receptor alpha (ERRα) was expressed at a relatively low level in adjacent intestinal areas, but at a high level of cells at a high level in a rare population, especially in the distal colon, where intestinal pain is considered deepened. This promotion of Erα in the colon relative to the small intestine suggests regional expertise in estrogen accountability. Therefore, he investigated how the loss of Erα affects the sensitivity and intestine function of the intestine.

While intestinal -deficient mutant mice showed no changes in gross metabolic parameters (eg, daily food intake, body weight), especially in women, colonic mobility and GI transit time were significantly intensified. Erα deficiency also reduced the mucosal auspicious sensitivity in women relative to men. Interestingly, estrogen treatment failed to increase intestinal sensitivity in mutant women, indicating that the ERK was central for estrogen-dependent increase of intestinal sensitivity.

Unexpectedly, EC cells were deficient in ERRH, but Erα was found to overlap fully with Pyy-expressed cells, especially in the disattal colon. Additional experiments have shown that Pyy1-36 Ovx can fully restore intestinal sensitivity in women or after the loss of estrogen signaling in the intestine epithelium, and that the Pyy1-36 locally acts to tie NPY1R on EC cells, which increases the activity of EC-Mukosal Circuit and the triggering of Sarponin releases Is.

Researchers also demonstrated that drug blocking this route-or at the level of NPY1R or serotonin 5HT3R, left-Astrogen-and Pyy1-36- Appeared to be induced intestinal hypersensitivity. These findings strengthen the central role of the route in the mediation of pain signaling.

Finally, the researchers identified estrogen-respondent goals that could modify intestinal sensitivity by ordering L-cells from vehicles or EB-walled OVX women. This revealed several goals sensitive to estrogen, including the known Erα goals. Overall, 248 genes were upgraded and 35 downgrated, highlighting a comprehensive transcriptional response in L-cells, while only a few estrogen-respondent genes were identified in sorted EC cells.

Short-chain fatty acid (SCFA) receptor encountered by olfactory receptor 78 (OLFR78) emerged as a top hit, and its expression in L-cells on estrogen treatment was confirmed. However, OLFR 78 was unchanged in EC cells after estrogen treatment. Prepare female intestinal organs with estrogen and treat them with acetate (OLFR78 ligand).

conclusion

Simultaneously, findings show how estrogen signaling controls parasin interaction between two EEC sub -factories, which illuminates the mechanism of increased intestinal sensitivity in women. Pyy1-36 from L cells starts cellular cascade by increasing serotonorous tone in EC cells, which activates nearby mucosal spinal efforts. Estrogen plays an important role in triggering these phenomena by increasing the PYY release and triggering these phenomena by increasing the sensitivity of L cells for bacterial metabolites (SCFAS) through OLFR78.

The results also suggest medical strategies for conditions such as irritable bowel syndrome (IBS), including joint use of NPY1R and 5HT3R, as well as dietary interventions that reduce SCFA production (eg, low fodmap diet).

*Important Information: Biorxiv Publishes preliminary scientific reports that are not reviewed by colleagues and therefore, it should be considered as decisive, guide clinical practice/health related behavior, or established information.