Abstract
There are significant gender-based differences in cardiac diseases such as cardiac hypertrophy and hypertensive heart disease [1–3]. As the incidence of cardiac disease in women increases after the menopause [1], it has been postulated that estrogen plays a role in the morbidity of heart disease. The mechanisms how estrogen affects this process is currently under investigation [4,5]. Recent findings have demonstrated that estrogen exerts a large array of non-genomic and genomic effects on the myocardium [4–7]. In this context, we have previously shown that cardiac myocytes and cardiac fibroblasts contain functional estrogen receptors (ER) which activate a subset of cardiac target genes i.e connexin 43 [4]. The ER belongs to a class of steroid hormone receptor which are activated upon ligand binding, however recent observations demonstrate that the ER is also activated through phosphorylation-dependent signaling pathways [8,9]. These signaling pathways are shared with a variety of different growth factors i.e. the insulin-like growth factor (IGF-1). Growth factors like IGF-1 activate intracytoplasmic signal transduction cascades through binding of specific plasma-membrane bound receptor-tyrosine kinases [10]. The level of IGF-1 has been associated with cardiac disease i.e. hypertrophic cardiomyopathy in human patients has been linked with overexpression of IGF-1 in cardiac tissue [11]. Furthermore, the specific overexpression of the IGF-1 cDNA in mice leads to cardiac hypertrophy and reveals gender-based differences [10]. Interestingly, IGF-1 has also been shown to activate the ER in tumor cell lines like human breast cancer cells [12]. Therefore, we hypothesized that the signaling pathway of IGF-1 and estrogen might also interact in myogenic growth and differentiation and that this interaction may well play a role in the pathogenesis of cardiac disease. To further elucidate these mechanisms we investigated the expression of ERs and the influence of IGF-1 on ER activation in an estrogen-responsive myogenic cell model (L6 rat skeletal myoblasts) [13].
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Grohé, C., Meyer, R., Vetter, H. (1999). Crosstalk between the Estrogen Receptor and the Insulin-Like Growth Factor (IGF-1) Receptor. Implications for Cardiac Disease. In: Doevendans, P.A., Reneman, R.S., van Bilsen, M. (eds) Cardiovascular Specific Gene Expression. Developments in Cardiovascular Medicine, vol 214. Springer, Dordrecht. https://doi.org/10.1007/978-94-015-9321-2_19
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DOI: https://doi.org/10.1007/978-94-015-9321-2_19
Publisher Name: Springer, Dordrecht
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