Navegando por Palavras-chave "Proteína Dissulfeto Isomerase"

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    Proteínas dissulfeto isomerase (PDIs): relação com hormônios esteroidais sexuais e função epididimária
    (Universidade Federal de São Paulo (UNIFESP), 2019-07-25) Fernandes, Samuel Guilerme [UNIFESP]; Winston, Maria Christina Werneck De Avellar [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Protein disulfide isomerase (PDI) family is a member of the thioredoxin protein superfamily. There are at least 21 genes encoding PDIs that greatly vary in their protein structure, tissue expression, and cellular distribution. PDIs are multifunctional chaperones primarily involved in the catalysis of thiol-disulfide exchange reactions for protein folding, which are rate-limiting steps for protein maturation in the endoplasmic reticulum. In addition to their roles in different physiological processes, including sperm maturation and male fertility, PDIs have also been associated with several pathologies. The mechanisms by which PDIs regulate the male reproductive function in health and disease, however, are still poorly understood. Surprisingly, we observed in pilot studies that transcripts encoded by at least 20 Pdi genes are present in the caput epididymis from adult rats. Considering the crucial role of the epididymis to sperm function, we set to uncover in the present study the expression pattern and androgen regulation of a subset of Pdi genes (P4hb, Pdia3, Pdia5, Pdia6, Pdilt and Erp29) in the epididymis of developing rats. Firstly, we detected Pdi mRNAs in the Wolffian duct (embryonic epididymal precursor) from fetuses at embryonic ages (e) e17.5 and e20.5, a temporal window when epididymal morphogenesis occurs; in contrast to similar mRNA levels of Pdilt and Erp29 genes, upregulation of P4hb, Pdia3, Pdia5 and Pdia6 mRNA was observed in WD from e17.5 to e20.5. Next, we observed that these Pdi genes were differentially expressed during postnatal in epididymis from neonatal rats (pnd1, pnd5, pnd10 and pnd20; whole epididymis) and in epididymal regions from sexually immature (pnd40) and mature rats (adult, pnd120); in these studies, only Pdia3, Pdia5 and Pdia6 genes displayed significant age-related changes in their transcript levels. Surgical castration, followed or not by testosterone replacement and efferent ductules ligation were then performed in adult rats to evaluate Pdi gene modulation by androgens and/or testicular factors, respectively. The downregulation of Pdia3, Pdia5, Pdia6 and Erp29 transcripts in androgen-deprived caput epididymis was prevented by testosterone replacement, indicating their positive regulation by androgens. Conversely, the castration-induced decrease in caput epididymis P4hb and Pdilt mRNA levels were only partially or not restored, respectively, by the androgen treatment. P4hb was the only Pdi gene to be downregulated following efferent ductules ligation, suggesting its modulation by both androgens and testicular factors. The bioinformatic-based analysis revealed potential role for androgen/AR signaling pathways in the regulatory modulation of some, but not all Pdi genes. Lastly, immunohistochemistry was conducted with antibodies against two PDIs, i.e. PDILT and P4HB; both PDIs were immunolocalized in epithelial and non-epithelial cells along the adult epididymis and also in the luminal spermatozoa. Altogether, our results give support for PDIs as novel players in the developing and adult epididymis.