Abstract
Ovarian sex steroids can modulate new vessel formation and development, and the clarification of the underlying mechanism will provide insight into neovascularization-related physiological changes and pathological conditions. Unlike estrogen, which mainly promotes neovascularization through activating classic post-receptor signaling pathways, progesterone (P4) regulates a variety of downstream factors with angiogenic or antiangiogenic effects, exerting various influences on neovascularization. Furthermore, diverse progestins, the synthetic progesterone receptor (PR) agonists structurally related to P4, have been used in numerous studies, which could contribute to unequal actions. As a result, there have been many conflicting observations in the past, making it difficult for researchers to define the exact role of progestogens (PR agonists including naturally occurring P4 and synthetic progestins). This review summarizes available evidence for progestogen-mediated neovascularization under physiological and pathological circumstances, and attempts to elaborate their functional characteristics and regulatory patterns from a comprehensive perspective.
Highlights
Progestogens in Neovascularization?Neovascularization is composed of two conceptions: angiogenesis and vasculogenesis.New capillaries that originate from existing capillaries are called angiogenesis, while vasculogenesis indicates new vessels initially derived from endothelial progenitor cells (EPCs). angiogenesis has been proven to be a major part of neovascularization in most situations, these two conceptions coexist and complement each other [1]
Progestogens exert various effects on neovascularization, but conflicting observations in previous studies mean an accurate understanding of their functional characteristics and regulatory patterns remains elusive
The level of progesterone receptor (PR) probably is the cause, and PR expression is influenced by sex hormones; E2 directly regulates the transcription of PR, and P4 exerts a dosedependent effect on PR expression [20]
Summary
Neovascularization is composed of two conceptions: angiogenesis and vasculogenesis. New capillaries that originate from existing capillaries are called angiogenesis, while vasculogenesis indicates new vessels initially derived from endothelial progenitor cells (EPCs). Biomolecules 2021, 11, 1686 and paracrine or juxtacrine signalings of EPCs and ECs. Investigating the role of sex steroids will provide insight into neovascularization-related physiological changes and pathological conditions. In addition to naturally occurring P4, a variety of synthetic progestins are widely used as PR agonists in in vitro or in vivo PR signaling studies, because synthetic progestins possess P4-like structures and effects, as well as great receptor binding affinities and metabolisms [15]. These PR agonists, including naturally occurring P4 and progestins, are classified as progestogens [15]. The aim of this review is to discuss their influence on neovascularization, and to summarize available evidence on the role of progestogens in physiological and pathological neovascularization, yielding an accurate understanding on their functional characteristics and regulatory patterns
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