Regulation of Sertoli cell activin A and inhibin B by tumour necrosis factor α and interleukin 1α: interaction with follicle-stimulating hormone/adenosine 3',5'-cyclic phosphate signalling.
Regulation of crucial events during spermatogenesis involves dynamic changes in cytokine production and interactions across the cycle of the seminiferous epithelium. Regulation of activin A and inhibin B production by the inflammatory cytokines, tumour necrosis factor α (TNFα) and interleukin 1α (IL1α), alone and in conjunction with FSH or a cAMP analogue (dibutyryl cAMP), was examined in cultures of Sertoli cells from 20-day old rats. Both TNFα and IL1α stimulated activin A secretion and expression of its subunit (β(A)) mRNA, and suppressed inhibin B secretion and expression of its subunit (α and β(B)) mRNAs. The actions of TNFα and IL1α were opposed by FSH and dibutyryl cAMP. Both cytokines inhibited FSH/dibutyryl cAMP-stimulated inhibin B secretion and mRNA expression as well as stem cell factor mRNA expression. Both cytokines also inhibited FSH-induced cAMP production, and reduced baseline FSH receptor mRNA expression. These data highlight the reciprocal relationship that exists between FSH/cAMP signalling and inflammatory cytokine signalling pathways in the control of Sertoli cell function, and production of activin A/inhibin B in particular. It is anticipated that these interactions play important roles in the fine control of events during the cycle of the seminiferous epithelium and in the inhibition of spermatogenesis during inflammation.
Centre for Reproduction and Development, Monash Institute of Medical Research, Monash University, Melbourne, Victoria, Australia.
Saito
S
Kazutaka
Wendy R
WR
Winnall
Julie A
JA
Muir
Mark P
MP
Hedger
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015536:Down-Regulation; D005640:Follicle Stimulating Hormone / Q000494:pharmacology* / Q000502:physiology; D028322:Inhibin-beta Subunits / Q000235:genetics / Q000378:metabolism*; D007265:Inhibins / Q000235:genetics / Q000378:metabolism*; D053582:Interleukin-1alpha / Q000494:pharmacology* / Q000502:physiology; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011962:Receptors, FSH / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D012708:Sertoli Cells; D015398:Signal Transduction; D013110:Sphingosine / Q000031:analogs & derivatives / Q000494:pharmacology; D019089:Stem Cell Factor / Q000235:genetics; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology* / Q000502:physiology; D015854:Up-Regulation
D053582:Interleukin-1alpha; C064769:N-acetylsphingosine; D010726:Phosphodiesterase Inhibitors; D021122:Protein Subunits; D011962:Receptors, FSH; D011994:Recombinant Proteins; D019089:Stem Cell Factor; D014409:Tumor Necrosis Factor-alpha; C422364:inhibin B; C103008:inhibin beta A subunit; D007265:Inhibins; D003994:Bucladesine; D005640:Follicle Stimulating Hormone; D028322:Inhibin-beta Subunits; D000242:Cyclic AMP; D013110:Sphingosine