Functional Segregation of Pancreatic Microcirculation Reveals Sex-Dependent Microhemodynamic Signatures

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.