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
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 many physiological processes vascularization is an important step, such as in embryo development, the female menstrual cycle, tissue repair processes, as well as in growth and differentiation of tissues   . However, when in pathological conditions (ischemic, inflammatory and neoplastic diseases) this process is called neoangiogenesis   . "
ABSTRACT: The formation of a tumor-associated vascular network is an important step in understanding the stages of tumor progression. This review aims to highlight the main markers of induction, proliferation and inhibition of angiogenesis, as well as the quantification of microvessel density, correlated with preclinical and clinical research in gynecologic cancers and also discussed related patents. Studies show that in the most advanced cases of gynecological cancers, biomarkers such as VEGF (Vascular Endothelial Growth Factor), MMP (Matrix Metalloproteinase), CD105 (Endoglin), TIMP (tissue inhibitors of metalloproteinases) and VASH (Vasohibin) are more expressed compared to healthy individuals. Continuous evaluation of these biomarkers in cancer cases could serve in the future as a basis for development of new therapeutic approaches, leading to a good response to cancer treatment, and thus increase survival of cancer patients.Recent Patents on Anti-Cancer Drug Discovery 09/2015; 10(3):298. DOI:10.2174/1574892810999150827153642 · 4.30 Impact Factor
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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). "
ABSTRACT: Cytokines are key regulators of ovarian physiology, particularly in relation to folliculogenesis and ovulation, where they contribute to creating an environment supporting follicle selection and growth. Their manifold functions include regulating cellular proliferation/differentiation, follicular survival/atresia, and oocyte maturation. Several cytokines, such as TGFβ-superfamily members, are involved at all stages of folliculogenesis while the production of others is stage-dependent. This review draws upon evidence from both human and animal models to highlight the species-specific roles at each milestone of follicular developmental. Given these pivotal roles and their ease of detection in follicular fluid, cytokines have been considered as attractive biomarkers of oocyte maturational status and of successful assisted reproductive outcome. Despite this, our understanding of cytokines and their interactions remains incomplete, and is still frequently limited to overly simplistic descriptions of their interrelationships. Given our increased appreciation of cytokine activity in complex and highly regulated networks, we put forward the case for using Bayesian modelling approaches to describe their hierarchical relationships in order to predict causal physiological interactions in vivo. Mol. Reprod. Dev. © 2013 Wiley Periodicals, Inc.Molecular Reproduction and Development 04/2014; 81(4). DOI:10.1002/mrd.22285 · 2.53 Impact Factor
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ABSTRACT: To compare the effects of human menopausal gonadotropins (hMG) and recombinant follicle stimulating hormone (rFSH) on transforming growth factor (TGF) β1 concentration in the rat ovary. Twenty-one fertile Wistar-Albino rats were divided into 3 groups of 7. Groups 1, 2 and 3 were injected with saline, hMG or rFSH, respectively, over 5 days, after which they underwent ovariectomy. Hematoxylin and eosin (H&E) staining was used for histological examination. TGF β1 staining levels in ovarian stroma, vessel walls, granulosa cells of Graafian follicles and corpus luteum cells were investigated immunohistochemically. On histological examination, the number of smaller antral follicles was higher in the control group, while there were more and larger antral follicles in the hyperstimulated groups. There were statistically significant differences in staining in vessel walls and granulosa cells between the control and stimulated groups. Both stimulation protocols caused an increased TGF β1 concentration in vessel walls, while there was weak staining in granulosa cells in the treatment groups compared to the control group (p<0.05). There were no significant differences in staining scores between the two treatment groups (p>0.05). The effects of two different gonadotropin preparations on TGF β1 concentrations in different localizations in the rat ovaries are comparable. It may be postulated that the luteinizing hormone (LH) content of hMG contributes little or nothing to the TGF β1 mediated angiogenesis.European journal of obstetrics, gynecology, and reproductive biology 04/2012; 163(1):35-8. DOI:10.1016/j.ejogrb.2012.03.016 · 1.70 Impact Factor
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