Abstract
For citation purposes: Laurentino S, Pinto P, Correia S, Cavaco JE, Canario AVM, Socorro S. Structural variants of sex steroid hormone receptors in the testis: from molecular biology to physiological roles. OA Biotechnology 2012 Dec 17;1(2):4. Licensee OA Publishing London 2012. Creative Commons Attribution License (CC-BY) Abstract Introduction Sex steroid hormones, androgens and oestrogens regulate diverse physiological processes by interacting with their intracellular protein receptors and modulating the expression of target genes. Classical sex steroid hormone receptors belong to the nuclear receptor superfamily, which forms the largest known family of transcription factors in eukaryotes. A common feature of sex steroid hormone receptors genes is the incidence of alternative splicing, a process that generates multiple variants from a single mRNA precursor molecule. This process facilitates the production of functionally distinct proteins and contributes to proteome diversity in higher eukaryotes. Herein we will critically review current information about the diversity of oestrogen receptors and androgen receptors variants, discussing their structural features and physiological functions. Conclusion The identification of structural variants of both ERs and ARs in healthy testis and a broad range of vertebrate species, highlights the newly revealed complexity of SSHRs signalling mechanisms in this tissue. Structural variants of sex steroid hormone receptors in the testis: from molecular biology to physiological roles
Highlights
Sex steroid hormones, androgens and oestrogens regulate diverse physiological processes by interacting with their intracellular protein receptors and modulating the expression of target genes
While the two oestrogen receptor (ER) subtypes (ERα and ERβ) have a typical steroid receptor structure, they are encoded by genes located on different chromosomes[5,6], sharing only 41%–65% of overall amino acid identity depending on the species being considered[2,4]
Steroid hormone receptors may establish protein–protein interactions with other sequence-specific transcription factors or establish cross-talk with signal transduction pathways that are activated by extracellular signals via membrane receptors [e.g., the G-protein coupled receptor (GPCR)] and the activation of protein kinase cascades[21,22,23]
Summary
Namely androgens and oestrogens, regulate multiple reproductive and non-reproductive processes by interacting with their cognate specific receptor protein and regulating the expression of target genes. While the two ER subtypes (ERα and ERβ) have a typical steroid receptor structure, they are encoded by genes located on different chromosomes[5,6], sharing only 41%–65% of overall amino acid identity depending on the species being considered[2,4] Both receptors exhibit similar binding affinity to 17β-oestradiol and display binding characteristics recognised for ER proteins; relative binding affinity for natural and synthetic oestrogens in addition to anti-oestrogenic compounds is higher than the binding affinity for androgens, progoestrogens or corticosteroids[7]. Alternative splicing is a widespread process in higher eukaryotes that facilitates the generation of distinct structural mRNA variants from a single gene, which in turn may produce functionally distinct protein isoforms in cell- or tissuespecific contexts[15,16] This critical review aims to provide an overview of existing information about alternative splice variants of ERs and ARs in the testis, from their molecular biology to phys-iological roles
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