Structural variants of sex steroid hormone receptors in the testis: from molecular biology to physiological roles

Abstract

IntroductionSex 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. ConclusionThe 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.

Effects of Estrogens and Estrogenic Disrupting Compounds on Fish Mineralized Tissues

“…In the classical model of estrogen actions ( Figure 2 A), ERs regulate gene expression in the nucleus of target cells by binding to estrogen-response elements (ERE) in the promoters of target genes [ 49 , 50 ]. Estrogens (as well as EDCs) can also act via alternative pathways (see Figure 2 B–D for details), and studies in mammals reveal the indirect regulation of gene expression by interaction with other transcription factors (TFs) or by binding to membrane receptors, which may result in changes in gene expression or in rapid non-genomic effects, such as the activation of specific enzymes [ 7 , 50 , 51 ].…”

“…In the classical model of estrogen actions ( Figure 2 A), ERs regulate gene expression in the nucleus of target cells by binding to estrogen-response elements (ERE) in the promoters of target genes [ 49 , 50 ]. Estrogens (as well as EDCs) can also act via alternative pathways (see Figure 2 B–D for details), and studies in mammals reveal the indirect regulation of gene expression by interaction with other transcription factors (TFs) or by binding to membrane receptors, which may result in changes in gene expression or in rapid non-genomic effects, such as the activation of specific enzymes [ 7 , 50 , 51 ]. The nature of the receptors mediating membrane-initiated actions of estrogens remains controversial, but probably includes both classical ERs and their variants, as well as novel membrane receptors, such as the G protein-coupled estrogen receptor 1 (GPER, formerly known as GPR30), recently characterized in mammals and fish [ 52 , 53 , 54 ].…”

“…Natural estrogens may compete with several EDCs (represented by different colors and shapes) for multiple receptors and pathways, resulting in a complex response that depends on the cellular context in terms of receptors and interacting proteins and, thus, may differ between tissues and circumstances. cAMP, cyclic AMP; PKA, protein kinase A; PLC, phospholipase C; IP3, inositol 1,4,5-triphosphate; DAG, diacylglycerol; PKC, protein kinase C. Adapted from [ 50 ].…”

Duplicated membrane estrogen receptors in the European sea bass (Dicentrarchus labrax): Phylogeny, expression and regulation throughout the reproductive cycle

“…In the classical model of action, estrogens diffuse through the cell membrane and interact with specific intracellular nuclear receptors, two of which, Esr1 and Esr2, exist in terrestrial vertebrates while in fish three forms, one Esr1 and two Esr2s (expressed from duplicate genes) have been detected [4]. The resulting ligand-receptor complex binds to specific response elements in the promoter regions of target genes and regulates their transcription, a process that can take hours or days to be completed [5,6].…”

“…Several alternative mechanisms of estrogen action have been described including indirect genomic effects through interaction with other transcription factors or rapid non-genomic effects initiated by binding to membrane receptors [5,7] that can produce effects within minutes [8]. No consensus exists about the identity of the membrane receptors mediating non-genomic effects of estrogens and they have been attributed to membrane sub-populations of nuclear estrogen receptors or to novel membrane receptors such as the G protein-coupled estrogen receptor, Gper (formerly known as Gpr30).…”