Claudin-11 expression and localisation is regulated by androgens in rat Sertoli cells in vitro

• Published in: Reproduction (Cambridge, England) Vol. 133; no. 6; pp. 1169 - 1179
• Main Authors: Kaitu’u-Lino, Tu’uhevaha J, Sluka, Pavel, Foo, Caroline F H, Stanton, Peter G
• Format: Journal Article
• Language: English
• Published: England Society for Reproduction and Fertility 01.06.2007; BioScientifica Ltd
• Subjects: Animals; Blood-Testis Barrier - drug effects; Cells, Cultured; Claudins; Follicle Stimulating Hormone - pharmacology; Immunohistochemistry; Male; Membrane Proteins - analysis; Membrane Proteins - genetics; Membrane Proteins - metabolism; Nerve Tissue Proteins - analysis; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Occludin; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - analysis; Sertoli Cells - chemistry; Sertoli Cells - drug effects; Sertoli Cells - metabolism; Testosterone - pharmacology; Tight Junctions - chemistry; Tight Junctions - drug effects; Tight Junctions - metabolism
• DOI: 10.1530/REP-06-0385
• ISSN: 1470-1626

Claudin-11 and occludin are protein components in tight junctions (TJs) between Sertoli cells which are important for the maintenance of the blood–testis barrier. Barrier formation occurs during puberty, with evidence suggesting hormonal regulation of both claudin-11 and occludin. This study aimed to investigate the regulation of claudin-11 and occludin mRNA expression by testosterone (T) and FSH and their immunolocalisation at rat Sertoli cell TJs in vitro, and to correlate any steroid regulation with the functional capacity of TJs. Sertoli cells formed functional TJs within 3 days as assessed by transepithelial electrical resistance (TER). Both T and dihydrotestosterone significantly (P < 0.01) increased TER twofold and claudin-11 mRNA two- to threefold within 3 days. FSH partially stimulated TER and claudin-11 mRNA, but estradiol had no effect. T also promoted claudin-11 localisation into extensive intercellular contacts. In contrast to claudin-11, Tand FSH did not change occludin mRNA expression, however, T promoted localisation of occludin at cell contacts in a similar manner to claudin-11. Addition of flutamide to T-stimulated cells caused a twofold decrease in both TER and claudin-11 mRNA expression, and resulted in the loss of both proteins from cell contacts. This effect was reversible following flutamide removal. It is concluded that androgens i) co-regulate claudin-11 mRNA expression and TER, implicating claudin-11 in TJ formation and ii) promote the localisation of claudin-11 and occludin at Sertoli cell contacts. Hence, the ability of androgens to maintain spermatogenesis in vivo is partly via their effects on TJ proteins and regulation of the blood–testis barrier.