Age-dependent stimulation of Leydig cell steroidogenesis by interleukin-1 isoforms.
Different isoforms of testicular interleukin-1 (IL-1) were analysed to determine whether there were differences in the ability to modulate rat Leydig cell steroidogenesis in vitro. Rat 17K IL-1alpha and IL-1beta, 32K IL-1alpha precursor (32proIL-1alpha) and a 24K splice variant (24proIL-1alpha) stimulated testosterone production by Leydig cells from 40- but not 80-day-old rats. The potency of the isoforms was IL-1alpha>IL-1beta>32proIL-1alpha>24proIL-1alpha, IL-1alpha being 50-fold more potent than IL-1beta. IL-1 receptor antagonist reversed the effects and IL-1 receptor type I mRNA was expressed by the responding Leydig cells, indicating a receptor mediated action. Inhibition of PKA and Ca(2+) channels abolished IL-1-induced steroidogenesis, while inhibition of PKC had no significant effect. Except for 24proIL-1alpha which was stimulatory, all IL-1 isoforms suppressed hCG-driven testosterone production. This inhibitory effect was abolished by androstendione, suggesting that P450c17 was suppressed by IL-1. Our results indicate that IL-1 plays a paracrine role in the regulation of Leydig cell steroidogenesis.
Svechnikov
K V
KV
Department of Woman and Child Health, Astrid Lindgren Children's Hospital, Pediatric Endocrinology Unit, Karolinska Institute and Hospital (Q2:08), SE-17176 Stockholm, Sweden. konstantin.svechnikov@kbh.ki.se
Sultana
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Söder
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D000375:Aging / Q000502:physiology*; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007546:Isoquinolines / Q000494:pharmacology; D007985:Leydig Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D013449:Sulfonamides; D013739:Testosterone / Q000096:biosynthesis* / Q000378:metabolism; D013997:Time Factors
D004791:Enzyme Inhibitors; D007375:Interleukin-1; D007546:Isoquinolines; D009281:Naphthalenes; D020033:Protein Isoforms; D017472:Receptors, Interleukin-1; D013449:Sulfonamides; D013739:Testosterone; D003994:Bucladesine; C058819:calphostin C; D009543:Nifedipine; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide