# Progesterone Receptor Expression in the Human Enteric Nervous System

## TL;DR

This study maps progesterone receptor expression in the human gut's nervous system, revealing sex- and age-related patterns that could impact gut-brain communication and neurodegenerative diseases.

## Contribution

The study provides the first detailed characterization of progesterone receptor expression in the human enteric nervous system, including regional, sex, and age variations.

## Key findings

- Progesterone receptors PR-A/B, PGRMC1, mPRα, and mPRβ are expressed in myenteric ganglion cells across all intestinal regions.
- Expression patterns show sex-specific differences and age-related downregulation.
- Progesterone signaling in the myenteric plexus suggests a hormonal role in gut-brain communication.

## Abstract

The enteric nervous system (ENS) is a critical component of the gut–brain axis, playing a pivotal role in gastrointestinal homeostasis and systemic health. Emerging evidence suggests that ENS dysfunction precedes central neurodegenerative disorders. Progesterone, known for its neuroprotective and anti-inflammatory properties in the central nervous system (CNS), has received growing attention for its potential role in ENS physiology. This study aimed to map the expression of nuclear and membrane-bound progesterone receptors in the human ENS, considering regional intestinal, sex, and age variations. Immunofluorescence and Reverse Transcription-Polymerase Chain Reaction (RT-PCR) were used to evaluate receptor distribution in anatomically distinct intestinal regions. Consistent expression of classical nuclear progesterone receptors (PR-A/B) and the non-classical Progesterone receptor membrane component 1 (PGRMC1) in myenteric ganglion cells across all intestinal segments was observed. RT-PCR confirmed the expression of PR-A/B, PGRMC1, mPRα, and mPRβ, with regional variations. Sex-specific patterns were evident along with age-related downregulation. Our findings provide a detailed characterization of progesterone receptor expression in human ENS, highlighting sex- and age-dependent regulation. The identification of progesterone signaling within the myenteric plexus suggests a hormonal influence in gut–brain communication. Targeting ENS progesterone receptors may open novel therapeutic avenues to modulate neurodegenerative CNS disorders via peripheral intervention along the gut–brain axis.