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Experimental varicocoele in rats affects mechanisms that control expression and function of the androgen receptor
Author(s) -
Soares T. S.,
Fernandes S. A. F.,
Lima M. L.,
Stumpp T.,
Schoorlemmer G. H.,
Lazari M. F. M.,
Porto C. S.
Publication year - 2013
Publication title -
andrology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.947
H-Index - 43
eISSN - 2047-2927
pISSN - 2047-2919
DOI - 10.1111/j.2047-2927.2013.00103.x
Subject(s) - androgen receptor , downregulation and upregulation , biology , endocrinology , andrology , medicine , gene , biochemistry , genetics , prostate cancer , cancer
Summary Varicocoele is an important cause of male infertility. Normal male reproductive function and fertility depends on a delicate balance between androgen receptor ( AR ) and the classic oestrogen receptors ESR 1 ( ER α) and ESR 2 ( ER β). Using a model of surgically induced varicocoele in rats, this study aimed to investigate the effects of varicocoele on the expression of AR , ESR 1, ESR 2 and G‐protein coupled oestrogen receptor ( GPER ). Varicocoele did not affect the m RNA and protein expression of ESR 1 and ESR 2 in both testes. Varicocoele did not affect the m RNA and protein expression of GPER in the right testis, but slightly reduced the m RNA and increased the protein levels in the left testis. Varicocoele did not affect the m RNA for AR , but reduced the protein levels in both testes. A proteomic approach was used in an attempt to find differentially expressed targets with possible correlation with AR downregulation. Varicocoele caused the differential expression of 29 proteins. Six proteins were upregulated, including the receptor for activated C kinase 1 ( RACK 1), and 23 were downregulated, including dihydrolipoamide dehydrogenase, alpha‐enolase and pyrophosphatase 1. Western blot analysis confirmed that varicocoele upregulated the expression of RACK 1, a protein involved with tyrosine phosphorylation and regulation of AR transcriptional activity, AR metabolism and dynamics of the blood–testis barrier. In conclusion, this study suggests that varicocoele affects mechanisms that control AR expression and function. This regulation of AR may play an important role in the varicocoele‐induced testicular dysfunction. Furthermore, varicocoele downregulates several other proteins in the testis that may be useful markers of spermatozoa function and male infertility.