In vitro regulation of rat Sertoli cell inhibin messenger RNA levels by transforming growth factor-beta 1 and tumour necrosis factor alpha.
In the present study, we examined the in vitro regulation of 20-day-old rat Sertoli cell inhibin alpha- and beta B-subunits mRNA levels by transforming growth factor-beta 1 (TGF-beta 1) and tumour necrosis factor alpha (TNF alpha), two factors produced in the testis. Addition of TGF-beta 1 to highly purified cultured Sertoli cells resulted in a time- and dose-dependent enhancement in the alpha-subunit mRNA levels (ED50 = 2.4 pM; maximal increase of 2.6-fold after 48 h of treatment), without affecting the beta B-subunit mRNA levels. Similarly, activin A up-regulated the alpha- but did not modulate the beta B-subunit mRNA levels. By contrast, TNF alpha decreased in a time- and dose-dependent fashion the mRNA levels of the two inhibin subunits alpha and beta B (IC50 = 29 pM for both subunits; maximal decrease of 4.4- and of 4-fold after 72 and 24 h of treatment for respectively the alpha- and beta B-subunits). The effects of TGF-beta 1 and TNF alpha on inhibin mRNA levels occurred within a dose range that might be expected under physiological conditions. In addition, TGF-beta 1-treated Sertoli cells responded to FSH or dibutyryl cyclic AMP ((Bu)2cAMP) by a further and significant additive increase of the alpha-subunit mRNA levels. TNF alpha-treated Sertoli cells responded significantly to FSH and to (Bu)2cAMP, thus attenuating the inhibitory action of TNF alpha on the alpha-inhibin mRNA levels. Together, the present findings emphasize the ability of some local growth factors to modulate the effects of FSH on Sertoli cell function.
Le Magueresse-Battistoni
B
B
INSERM U 407, Centre Hospitalier Lyon-Sud, Pierre-Bénite, France.
Morera
A M
AM
Benahmed
M
M
D028341:Activins; D000818:Animals; D015152:Blotting, Northern; D003994:Bucladesine / Q000494:pharmacology; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005640:Follicle Stimulating Hormone / Q000494:pharmacology; D006133:Growth Substances / Q000494:pharmacology; D007265:Inhibins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012708:Sertoli Cells / Q000187:drug effects / Q000276:immunology*; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016207:Cytokines; D006133:Growth Substances; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D028341:Activins; D007265:Inhibins; D003994:Bucladesine; D005640:Follicle Stimulating Hormone