Activator protein-1 in human male germ cell apoptosis.
Apoptosis limits germ cell number in the testis, and its dysregulation is associated with male infertility. Here, we evaluated the role of the transcription factor activator protein 1 (AP-1) in male germ cell apoptosis in a culture of human seminiferous tubules. AP-1 DNA-binding activity increased in cultured tubules within 2.5 h, which was earlier than the onset of apoptosis as detected by caspase 3 activation and apoptotic DNA fragmentation. The c-Jun, c-Fos and JunD proteins were detected in the Sertoli cell nuclei, whereas apoptosis occurred in the germ cells. Follicle-stimulating hormone (FSH), whose receptors are expressed in the Sertoli cells, inhibited germ cell apoptosis and concomitantly suppressed AP-1 DNA-binding activity, but had no effect on nuclear factor kappaB (NF-kappaB) activation. These results suggest that AP-1 transcription factors are involved in the Sertoli cell-mediated control of germ cell apoptosis, and that inhibition of germ cell apoptosis by FSH appears to involve suppression of AP-1 activation.
Suomalainen
Laura
L
Programme for Developmental and Reproductive Biology, Biomedicum Helsinki and Hospital for Children and Adolescents, University of Helsinki, FIN-00029, Helsinki, Finland. laura.suomalainen@hus.fi
Dunkel
Leo
L
Ketola
Ilkka
I
Eriksson
Minna
M
Erkkilä
Krista
K
Oksjoki
Riina
R
Taari
Kimmo
K
Heikinheimo
Markku
M
Pentikäinen
Virve
V
D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D053938:DNA Fragmentation; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000378:metabolism; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D005854:Germ Cells / Q000166:cytology / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D011944:Receptors, Androgen / Q000378:metabolism; D012671:Seminiferous Tubules / Q000166:cytology / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism*
D004791:Enzyme Inhibitors; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D011944:Receptors, Androgen; D018808:Transcription Factor AP-1; D005640:Follicle Stimulating Hormone; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases