Progesterone signaling in cardio-renal physiology and pathophysiology

Progesterone is a multifunctional steroid hormone essential for reproductive function, yet its roles in cardiovascular and renal physiology remain comparatively less understood than those of estrogen. While its classical actions in regulating the menstrual cycle, promoting endometrial receptivity, and maintaining pregnancy are well-established, progesterone also signals through both genomic pathways via nuclear receptors, and non-genomic mechanisms via membrane receptors. These receptors are expressed outside of reproductive tissues, including the vasculature, heart, and kidney, supporting broader systemic effects of progesterone that are not yet fully defined. When compared to the current understanding of estrogen-mediated regulation in these tissues, the mechanisms conferring progesterone-mediated regulation of cardiovascular and renal function are less well studied. This review explores the contemporary understanding of progesterone signaling on cardiorenal physiology and pathophysiology in females and males, highlighting the need for enhanced methodological reporting in studies in this field and further investigation into the integrative roles of progesterone signaling.