Disruption in the expression and immunolocalisation of steroid receptors and steroidogenic enzymes in letrozole-induced polycystic ovaries in rat
Francisco M. Zurvarra A , Natalia R. Salvetti A B , J. Ian Mason C , Melisa M. L. Velazquez A , Natalia S. Alfaro A and Hugo H. Ortega A B DA Department of Morphological Sciences and Center for Experimental Biology and Laboratory Animals Sciences, Faculty of Veterinary Sciences, Universidad Nacional del Litoral, Argentina.
B Argentine National Research Council (CONICET), Esperanza (3080), Santa Fe, Argentina.
C Centre for Reproductive Biology, The Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, EH16 4TJ, UK.
D Corresponding author. Email: hhortega@fcv.unl.edu.ar
Reproduction, Fertility and Development 21(7) 827-839 https://doi.org/10.1071/RD09026
Submitted: 7 February 2009 Accepted: 17 May 2009 Published: 17 July 2009
Abstract
The objective of the present study was to characterise the expression and tissue distribution of steroid receptors (oestrogen receptor-α and –β (ERα, ERβ), androgen receptor (AR) and progesterone receptor (PR)) and steroidogenic enzymes (P450 aromatase (P450arom), 3β-hydroxysteroid dehydrogenase (3β-HSD) and steroidogenic acute regulatory protein (StAR)) in letrozole-induced polycystic ovaries of rats. Changes in serum hormone levels, protein expression in whole ovaries by western blot analysis and protein localisation by immunohistochemistry were determined in female rats treated with the aromatase inhibitor letrozole and compared with controls in proestrous and diestrous rats. Increases in the serum LH, FSH and testosterone concentrations were observed in letrozole-treated rats whereas serum oestradiol and progesterone levels were reduced. Protein expression as analysed by western immunoblot was consistent with the immunohistochemical data. Letrozole treatment induced an increase in the expression of AR, StAR and 3β-HSD and a decrease in ERβ. ERα, PR and P450arom showed partial changes in relation to some cycle stages. These results indicate that cystogenesis in this experimental model is characterised by changes in steroid receptors and steroidogenic enzyme expression that may be essential to proper ovarian functioning and are in agreement with similar changes observed in women with PCOS.
Additional keywords: 3β-hydroxysteroid dehydrogenase, aromatase, polycystic ovarian syndrome, StAR, steroid receptors.
Acknowledgements
We are very grateful to Dr Pablo Beldomenico for critical reading of the manuscript. Also we thank the National Hormone and Pituitary Program of the National Institute of Diabetes and Digestive and Kidney Diseases and Dr A. F. Parlow for the RIA kits, and Dr Damasia Becu-Villalobos (CONICET) for valuable RIA contributions. The technical support of Celina Baravalle in obtaining experimental animals and the provision of Letrozole by ASPEN Argentina is gratefully acknowledged. This study was supported by grants from the National University of Litoral (CAID Program 2006).
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