Effects of the oestrogen receptor antagonist Fulvestrant on expression of genes that affect organization of the epididymal epithelium.
The role of oestrogens in epididymal function is still unclear. Knockout of the oestrogen receptor ESR1 (Esr1(-/-) ) or treatment with the anti-oestrogen Fulvestrant affect epididymal milieu and sperm motility. We investigated the effect of in vivo treatment of rats with Fulvestrant on: (i) expression of genes that may be important for the architecture and function of the epididymal epithelium: prominins 1 and 2, metalloproteinase 7, claudin 7, beta-catenin and cadherin 13, and (ii) levels of oestradiol and testosterone, and expression of oestrogen and androgen receptors, in the initial segment (IS), caput, corpus and cauda epididymis. Fulvestrant (i) reduced gene expression of prominin 1 (variant 1) in the caput, reduced prominin 1 protein content in the caput epididymis and in the efferent ductules, and increased the localization of prominin 1 in microvilli of the caput and corpus; (ii) reduced gene expression of prominin 2 in the corpus and cauda epididymis; (iii) increased the metalloproteinase 7 content in the apical region of principal cells from IS/caput; (iv) reduced in the corpus epididymis, but increased in the efferent ductules, the cadherin 13 mRNA level; (v) reduced testosterone but increased oestradiol levels in the corpus and cauda; (vi) increased the androgen receptor protein content in all regions of the epididymis, and the oestrogen receptor GPER in the corpus and cauda epididymis. In conclusion, treatment with Fulvestrant induced regional-specific changes in hormonal and steroid receptor content, and affected expression of proteins important for epithelial organization and absorption/secretion. The mechanisms of oestrogen action may differ among epididymal regions, which may contribute to determine region-specific sperm functions.
Section of Experimental Endocrinology, Department of Pharmacology, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
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Fernandes
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Nascimento
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Siu
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Oliveira
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Lazari
D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D004822:Epididymis / Q000187:drug effects* / Q000378:metabolism; D004958:Estradiol / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D065171:Estrogen Receptor Antagonists / Q000494:pharmacology*; D000077267:Fulvestrant; D006023:Glycoproteins / Q000096:biosynthesis; D008297:Male; D020783:Matrix Metalloproteinase 7 / Q000096:biosynthesis; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D010455:Peptides; D017208:Rats, Wistar; D011960:Receptors, Estrogen / Q000378:metabolism; D013739:Testosterone / Q000378:metabolism
D000071916:AC133 Antigen; D015703:Antigens, CD; D065171:Estrogen Receptor Antagonists; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D010455:Peptides; C000606025:Prom1 protein, rat; C473221:Prom2 protein, rat; D011960:Receptors, Estrogen; D000077267:Fulvestrant; D013739:Testosterone; D004958:Estradiol; D020783:Matrix Metalloproteinase 7
animal models; epididymis; gene expression; oestrogens; rat