Androgens and postmeiotic germ cells regulate claudin-11 expression in rat Sertoli cells.
In the present study we investigated whether fetal exposure to flutamide affected messenger and protein levels of claudin-11, a key Sertoli cell factor in the establishment of the hemotesticular barrier, at the time of two key events of postnatal testis development: 1) before puberty (postnatal d 14) during the establishment of the hemotesticular barrier, and 2) at the adult age (postnatal d 90) at the time of full spermatogenesis. The data obtained show that claudin-11 expression was inhibited in prepubertal rat testes exposed in utero to 2 and 10 mg/kg x d flutamide. However, in adult testes, the inhibition was observed only with 2, and not with 10, mg/kg x d of the antiandrogen. It is shown here that these differences between prepubertal and adult testes could be related to dual and opposed regulation of claudin-11 expression resulting from positive control by androgens and an inhibitory effect of postmeiotic germ cells. Indeed, testosterone is shown to stimulate claudin-11 expression in cultured Sertoli cells in a dose- and time-dependent manner (maximum effect with 0.06 microm after 72 h of treatment). In contrast, postmeiotic germ cells potentially exert a negative effect on claudin-11 expression, because adult rat testes depleted in spermatids (after local irradiation) displayed increased claudin-11 expression, whereas in a model of cocultured Sertoli and germ cells, spermatids, but not spermatocytes, inhibited claudin-11 expression. The apparent absence of claudin-11 expression changes in adult rat testes exposed to 10 mg/kg x d flutamide therefore could result from the antagonistic effects of 1) the inhibitory action of the antiandrogen and 2) the stimulatory effect of the apoptotic germ cells on claudin-11 expression. Together, due to the key role of claudin-11 in the hemotesticular barrier, the present findings suggest that such regulatory mechanisms may potentially affect this barrier (re)modeling during spermatogenesis.
Florin
Anne
A
Institut National de la Santé et de la Recherche Médicale, Unité 407, Faculté de Médecine Lyon-Sud, BP 12, 69921 Oullins Cedex, France.
Maire
Magali
M
Bozec
Aline
A
Hellani
Ali
A
Chater
Sonia
S
Bars
Remi
R
Chuzel
Franck
F
Benahmed
Mohamed
M
D000728:Androgens / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D057167:Claudins; D018920:Coculture Techniques; D015536:Down-Regulation; D005260:Female; D005485:Flutamide / Q000737:chemistry / Q000494:pharmacology; D005786:Gene Expression Regulation; D005854:Germ Cells / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D008297:Male; D008540:Meiosis; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics*; D012313:RNA / Q000737:chemistry; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012708:Sertoli Cells / Q000378:metabolism*; D013091:Spermatogenesis; D013737:Testis / Q000254:growth & development / Q000378:metabolism; D013997:Time Factors
D000728:Androgens; D057167:Claudins; C492353:Cldn11 protein, rat; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D012313:RNA; D005485:Flutamide