# Functional Segregation of Pancreatic Microcirculation Reveals Sex‐Dependent Microhemodynamic Signatures

## TL;DR

The pancreatic microcirculation shows sex-specific differences in blood flow regulation, influenced by hormones and genetic factors.

## Contribution

The study reveals sex-dependent microhemodynamic signatures in the pancreatic exocrine compartment linked to steroid-hormone interactions.

## Key findings

- Male pancreatic blood flow is directly coupled to systemic blood pressure, while females show ERβ-mediated oscillatory patterns.
- Sexual dimorphism in microcirculation is anatomically restricted to the exocrine compartment, not the endocrine islets.
- Genetic background modulates steroid responsiveness and affects microvascular adaptability.

## Abstract

The microcirculation is a determinant of organ function, translating systemic signals into local physiological responses. However, whether the regulation of microhemodynamics is sexually dimorphic within the pancreas has remained unknown. Here, using a multi‐scale approach in healthy mice, we report a sexual dimorphism in pancreatic microhemodynamics that is anatomically restricted to the exocrine compartment, defined by divergent expression of the endothelial marker CD31 and estrogen receptor ERβ, whereas the endocrine islet microvasculature remains conserved between sexes. We demonstrate that microhemodynamic dimorphism is functionally coupled to divergent systemic steroid hormone profiles, a male signature characterized by elevated androgens and steroidogenic precursors, and a female signature dominated by glucocorticoids and estrogen metabolites. The distinction manifests as fundamentally different regulatory principles for vascular control, where pancreatic blood flow in males is directly coupled to systemic blood pressure, whereas in females, the relationship is defined by correlations between blood pressure and the oscillatory components of microhemodynamics. Collectively, our data identify the pancreatic microcirculation as a primary site of physiological sexual dimorphism and establish its role as a fundamental conduit for translating the systemic hormonal milieu into sex‐specific organ homeostasis.

Pancreatic exocrine microcirculation exhibits sexual dimorphism arising from steroid–genetic interactions. Laser Doppler flowmetry combined with wavelet analysis identifies a male passive coupling phenotype aligned with systemic pressure and a female active vasomotion phenotype driven by ERβ‐mediated, NO‐dependent oscillations. Genetic background modulates steroid responsiveness that influences microvascular adaptability.