Expression of oestrogen receptor a and b is higher in skeletal muscle of highly endurance-trained than of moderately active men A. Wiik, 1 T. Gustafsson, 1,2 M. Esbjo ¨ rnsson, 1 O. Johansson, 3 M. Ekman, 3 C. J. Sundberg 2 and E. Jansson 1 1 Department of Laboratory Medicine, Division of Clinical Physiology, Karolinska Institutet, Stockholm, Sweden 2 Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden 3 Department of Neuroscience, The Experimental Dermatology Unit, Karolinska Institutet, Stockholm, Sweden Received 21 June 2004, accepted 22 February 2005 Correspondence: A. Wiik, Division of Clinical Physiology, Karolinska University Hospital, Huddinge, 141 86 Stockholm, Sweden. E-mail: anna.wiik@labmed.ki.se Abstract Aim: Two known oestrogen receptors (ERs), ERa and the recently cloned ERb, are expressed in the human skeletal muscle of both males and females. The effects of oestrogen and the role of ERs in skeletal muscle tissue are not well known. Oestrogen receptors and some of their target genes are involved in angiogenic processes. It was hypothesized that ERs are expressed at a higher level in a group with higher oxidative capacity, and that such an enhanced expression would parallel expression of the angiogenic factor – vascular endothelial growth factor (VEGF). Method: Muscle biopsies were taken from vastus lateralis in 10 highly endurance-trained males and 10 moderately active males and analysed for the expression of ERs and VEGF. Results: The major findings in the present study were the higher mRNA levels of ERa, ERb and VEGF in the highly endurance-trained than in the moderately active group. Conclusion: These data suggest that the greater mRNA expression of ERa and ERb and the oestrogen-associated angiogenic factor VEGF support the hypothesis of an involvement of ERs in the adaptation of skeletal muscle to endurance training. Keywords capillarization, gene expression, immunohistochemistry, oxida- tive capacity, physical exercise, vascular endothelial growth factor. The adaptations to endurance exercise have been well characterized and include tissue-specific changes, reduced blood lipid levels and blood pressure as well as increased insulin sensitivity and endothelial function. It has been suggested that tissue specific changes such as increased mitochondrial density and amount of capil- laries in skeletal muscle contribute to these processes. Possible links between exercise induced stimulus, tissue gene expression and vascular remodelling in responses to endurance training include genes such as vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase, and endothelin-1, which regulate vas- cular remodelling and are activated by exercise (Maeda et al. 1998, Gustafsson et al. 1999, Roberts et al. 1999). Just like physical activity oestrogen reduces blood lipid levels and blood pressure as well as increases insulin sensitivity and endothelial function (Farhat et al. 1996, Wong & Wong 1999). Interestingly, oestrogen transcriptionally activates similar genes as does exercise (Mendelsohn 2002). Thus, considering that physical activity and oestrogen have actions in common, the question whether oestrogen signalling is induced by physical exercise and thus could be involved in down- stream exercise-induced gene expression arises. The two oestrogen receptors (ERs) ERa and ERb are expressed at the mRNA level in human skeletal muscle Acta Physiol Scand 2005, 184, 105–112 Ó 2005 Scandinavian Physiological Society 105