Signaling Through FSH Receptors on Human Umbilical Vein Endothelial Cells Promotes Angiogenesis

Abstract

Our studies reveal a novel role for FSHR in female reproductive physiology. Its ability to promote angiogenesis in placental endothelial cells suggests that the FSHR may have an influential role in pregnancy.

Evaluation of in vivo bioactivities of recombinant hypo- (FSH 21/18 ) and fully- (FSH 24 ) glycosylated human FSH glycoforms in Fshb null mice

“…Because FSH-receptors have been identified on non-gonadal cells including bone osteoclasts [54], tumor blood vessels [57], and uterine and placental cells [55, 56, 58, 59], it would be interesting to determine whether different FSH glycoforms bind and signal via FSH receptors in these non-gonadal cells. Most likely, FSH 21/18 and FSH 24 glycoforms may signal through different pathways in these different cell types.…”

Hypoglycosylated hFSH Has Greater Bioactivity Than Fully Glycosylated Recombinant hFSH in Human Granulosa Cells

“…Since clinical studies have found improved ovarian stimulation with mixtures of acidic and less acidic hFSH isoforms (16) it will be important to determine whether mixtures of hypo-glycosylated FSH and fully-glycosylated FSH contribute to enhanced or diminished biological responses. Understanding how FSH glycoforms direct activities in multiple FSH target tissues [ovary, bone (33,34), endothelium (35), uterus and placenta (36,37)] offers a unique opportunity to develop novel approaches for diagnosis and treatments to improve fertility and reduce age associated morbidity.…”

Revisiting the expression and function of follicle-stimulation hormone receptor in human umbilical vein endothelial cells

“…With regard to tumor vessel cells (primary and metastatic), it was suggested that FSHR might serve as a potential cellular marker of different tumors and provide a novel approach for targeted cancer therapy. Four-years after the report of FSHR expression in tumor vessel cells14, FSHR expression was demonstrated in human umbilical vein endothelial cells (HUVEC)15. HUVECs significantly responded to FSH treatment in a series of functional tests like tube formation, wound healing, cell migration and proliferation, nitric oxide production and cell survival15.…”

“…Four-years after the report of FSHR expression in tumor vessel cells14, FSHR expression was demonstrated in human umbilical vein endothelial cells (HUVEC)15. HUVECs significantly responded to FSH treatment in a series of functional tests like tube formation, wound healing, cell migration and proliferation, nitric oxide production and cell survival15. This allowed the authors of above study to propose that HUVECs express functional FSHR expression and that the FSH-FSHR activation promotes angiogenesis as effectively as the potent well-characterized angiogenic factor VEGF15.…”

“…HUVECs significantly responded to FSH treatment in a series of functional tests like tube formation, wound healing, cell migration and proliferation, nitric oxide production and cell survival15. This allowed the authors of above study to propose that HUVECs express functional FSHR expression and that the FSH-FSHR activation promotes angiogenesis as effectively as the potent well-characterized angiogenic factor VEGF15. Based on these functional data they further suggested that FSH-FSHR could have an influential role in placental development and healthy pregnancy15.…”