Table 2 In vitro and adult rodent evidence of sex hormone-mediated effects on Vegf
From: Sex, hormones and cerebrovascular function: from development to disorder
Hormone | Sex & model | Age | Finding | Refs |
|---|---|---|---|---|
Estrogen | in vivo Females OVX rats implanted with a 17β-estradiol slow-release pellet + exposed to a recombinant human VEGF patch on the cerebral cortex | 12–14 weeks old | Exposure to VEGF significantly increased BBB permeability in OVX + vehicle-treated animals. This effect was rescued by 17β-estradiol | [232] |
ERɑ or ERβ knockout female mice | 15 week old | Constitutive deletion of both ERɑ or ERβ decreased levels of Vegf, Kdr and Flt-1 in frontocortical tissues | [113] | |
in vivo OVX female mice orally treated with resveratrol (estrogen agonist) + middle cerebral artery occlusion (MCAO) | 10–11 weeks | Resveratrol pretreatment elevated tight junction protein levels and BBB integrity, resulting in reduced subsequent ischemic brain injury. MCAO-induced elevation of Vegf was attenuated by resveratrol, suggestive of neuroprotective effects mediated in part by ERs | [233] | |
in vivo OVX female rats subjected to global cerebral ischemia (GCI)  +  Treatment with GPER-1 agonist (G1) upon reperfusion by intracerebroventricular injection | Adult (age unspecified) | GCI induced BBB breakdown in the CA1, which was rescued by G1 treatment and concomitant with decreased Vegfa protein levels | [234] | |
in vitro Primary human endometrial epithelial cells transfected with human VEGF promoter-luciferase reporter +  Exposed to 17β-estradiol | N/A | Treatment induced a 3.8-fold increase in luciferase activity, demonstrating a regulatory role of 17β-estradiol in VEGF gene transcription | [114] | |
Progesterone | in vitro Primary human endometrial stromal cells | N/A | Genome-wide high-throughput sequencing of human endometrial stromal cells revealed a binding site for progesterone receptor B (PGR-B) upstream of the VEGF transcription start site Several angiogenesis-related genes were reported downstream of PGR-B, including VEGF | [115] |
Testosterone | in vitro Human endothelial progenitor cells (EPCs) isolated from peripheral blood of healthy adult men, exposed to dihydrotestosterone (DHT) | N/A | DHT, a bioactive metabolite of testosterone, promoted proliferation, adhesion and migration of EPCs as well as VEGF secretion | [235] |
in vitro Primary human umbilical endothelial cells (hUVECs) exposed to testosterone | N/A | Testosterone impacted hUVEC cell migration through AR-dependent mechanisms | [116] |