Regulation of the gap junction interplay during postnatal development in the rat epididymis.

Autor: Cyr DG; Laboratory for Reproductive Toxicology, INRS-Centre Armand-Frappier Santé Biotechnologie, Université du Québec, 531 Boul Des Prairies, Laval, Québec, H7V 1B7, Canada. daniel.cyr@inrs.ca.; Department of Anatomy and Cell Biology, McGill University, 3640 University St, Montreal, QC, H3A 0C7, Canada. daniel.cyr@inrs.ca.; Department of Obstetrics, Gynecology and Reproduction, Université Laval, Québec, QC, Canada. daniel.cyr@inrs.ca., Adam C; Laboratory for Reproductive Toxicology, INRS-Centre Armand-Frappier Santé Biotechnologie, Université du Québec, 531 Boul Des Prairies, Laval, Québec, H7V 1B7, Canada., Dufresne J; Laboratory for Reproductive Toxicology, INRS-Centre Armand-Frappier Santé Biotechnologie, Université du Québec, 531 Boul Des Prairies, Laval, Québec, H7V 1B7, Canada., Gregory M; Laboratory for Reproductive Toxicology, INRS-Centre Armand-Frappier Santé Biotechnologie, Université du Québec, 531 Boul Des Prairies, Laval, Québec, H7V 1B7, Canada.
Jazyk: angličtina
Zdroj: Cell and tissue research [Cell Tissue Res] 2024 Dec; Vol. 398 (3), pp. 191-206. Date of Electronic Publication: 2024 Oct 16.
DOI: 10.1007/s00441-024-03919-1
Abstrakt: During postnatal development of the rat epididymis, a change in the expression of gap junction proteins, or connexins (Cxs), occurs, in which Gjb2 (Cx26) and Gja1 (Cx43) levels in the proximal epididymis are decreased, while Gjb1 (Cx32), Gjb4 (Cx30.3) and Gjb5 (Cx31.1) levels increase. The mechanism(s) responsible for the switch in Cx expression is unknown. The aim of this study is to identify the mechanisms responsible for the decrease in GJB2 protein levels and the increase in other Cxs during postnatal development. Results indicate that decreased Gjb2 expression for 48 h does not alter the expression of other Cxs in RCE-1 principal cells, suggesting a lack of compensatory expression. Sequence analysis of both Gjb2 and Gjb1 promoters identified common multiple response elements to steroid hormones. Using RCE-1 cells, we observed that dexamethasone increased Gjb2 mRNA levels by twofold after 48 h, while estradiol had no effect. Orchidectomy in rats resulted in a significant increase in GJB2 and decreased GJB1 in the caput and corpus epididymidis. Changes in Cxs protein levels were prevented by testosterone in orchidectomized rats. Similar results were observed in the prostate, another androgen-receptive organ. LNCaP cells, which are androgen-responsive, showed that exogenous dihydrotestosterone (DHT) decreased Gjb2 mRNA levels by approximately 50% concomitant with a 1.5-fold increase in Gjb1 levels. Using a GJB1 promoter construct we showed that DHT could induce transactivation of the luciferase transgene, while transactivation of two GJB2 promoters were unaltered. Results indicate that androgens and glucocorticoids regulate the expression of epididymal Cxs.
Competing Interests: Declarations. Ethical approval: All the animal protocols used in this study were approved by the Institut National de la recherche Scientifique (INRS) university animal care committee according to the guidelines of the Canadian Council on Animal Care. Informed consent: All participants have given their verbal consent regarding their participation in this study and submission of this article. Summary statement: The expression of connexins during epididymal development is regulated by androgens which inhibit the expression of Gjb2 and Gja1 in principal cells and stimulate the expression of Gjb1, Gjb4 and Gjb5. Conflicts of interest: The authors declare that there is no financial or non-financial conflict of interest.
(© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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