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.
Kallabis et al. (Thu,) studied this question.