Potential role of follicle stimulating hormone (FSH) and transforming growth factor (TGF1) in the regulation of ovarian angiogenesis

Institute of Physiology, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
Journal of Cellular Physiology (Impact Factor: 3.84). 06/2011; 226(6):1608-19. DOI: 10.1002/jcp.22491
Source: PubMed


Angiogenesis occurs during ovarian follicle development and luteinization. Pituitary secreted FSH was reported to stimulate the expression of endothelial mitogen VEGF in granulosa cells. And, intraovarian cytokine transforming growth factor (TGF)β1 is known to facilitate FSH-induced differentiation of ovarian granulosa cells. This intrigues us to investigate the potential role of FSH and TGFβ1 regulation of granulosa cell function in relation to ovarian angiogenesis. Granulosa cells were isolated from gonadotropin-primed immature rats and treated once with FSH and/or TGFβ1 for 48 h, and the angiogenic potential of conditioned media (granulosa cell culture conditioned media; GCCM) was determined using an in vitro assay with aortic ring embedded in collagen gel and immunoblotting. FSH and TGFβ1 increased the secreted angiogenic activity in granulosa cells (FSH + TGFβ1 > FSH ≈ TGFβ1 >control) that was partly attributed to the increased secretion of pro-angiogenic factors VEGF and PDGF-B. This is further supported by the evidence that pre-treatment with inhibitor of VEGF receptor-2 (Ki8751) or PDGF receptor (AG1296) throughout or only during the first 2-day aortic ring culture period suppressed microvessel growth in GCCM-treated groups, and also inhibited the FSH + TGFβ1-GCCM-stimulated release of matrix remodeling-associated gelatinase activities. Interestingly, pre-treatment of AG1296 at late stage suppressed GCCM-induced microvessel growth and stability with demise of endothelial and mural cells. Together, we provide original findings that both FSH and TGFβ1 increased the secretion of VEGF and PDGF-B, and that in turn up-regulated the angiogenic activity in rat ovarian granulosa cells. This implicates that FSH and TGFβ1 play important roles in regulation of ovarian angiogenesis during follicle development.

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    • "In humans and rodents, they are secreted by theca and granulosa cell compartments and have similar effects, although their potency differs according to their target cell (Juengel and McNatty, 2005). TGF-b1 and TGF-b2 stimulate FSH-receptor expression in granulosa cells, and the former also synergises with FSH to stimulate VEGF production and promote angiogenesis (Dunkel et al., 1994; Kuo et al., 2011), suggesting a likely role in follicle selection. Further in vivo evidence from bovine models indicates that TGF-b1 inhibits oestradiol production in FSH-stimulated follicles, with a reduction in this inhibition considered to be permissive for the selection of a single, dominant follicle (Ouellette et al., 2005). "
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