Stimulation of steroidogenesis in immature rat Leydig cells evoked by interleukin-1alpha is potentiated by growth hormone and insulin-like growth factors.
The cytokine IL-1alpha is produced constitutively by the intact testis, but its function in this organ remains largely unknown. In this study we examined cooperation between IL-1alpha and GH and IGFs with regard to stimulation of steroidogenesis by Leydig cells from 40-d-old rats in vitro. IL-1alpha alone stimulated testosterone (T) and dihydrotestosterone (DHT) production. GH, IGF-I, or IGF-II alone was without effect on T production, but they were found to elevate DHT release, albeit without an obvious dose-response effect. Costimulation with IL-1alpha and GH or with IL-1alpha and IGF-I or IGF-II elevated the rate of steroidogenesis (both T and DHT) above that observed with IL-1alpha alone. GH was found to increase the level of IGF-I in the cultured Leydig cells, an effect that was potentiated by IL-1alpha. The costimulatory effect of GH on steroidogenesis was abolished by treatment with picropodophyllin, a specific inhibitor of the IGF-I receptor, indicating that the action of GH is mediated via IGF-I. Moreover, cells costimulated with IL-1alpha and GH exhibited a marked decrease in the level of intact IGF-binding protein-3 in the culture medium due to the induction of proteolytic activity toward this binding protein. In contrast, secretion of IGF-binding protein-2 was increased by such costimulation. These findings suggest that the stimulation of steroidogenesis in Leydig cells evoked by GH and IGFs requires cooperation with IL-1alpha. This cooperation may play an important role in connection with postnatal Leydig cell maturation and steroidogenesis.
Colón
Eugenia
E
Department of Woman and Child Health, Pediatric Endocrinology Unit, Astrid Lindgren Children's Hospital, Karolinska Institute and Hospital, S-171 76 Stockholm, Sweden.
Svechnikov
Konstantin V
KV
Carlsson-Skwirut
Christine
C
Bang
Peter
P
Soder
Olle
O
D000728:Androgens / Q000096:biosynthesis*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D013196:Dihydrotestosterone / Q000378:metabolism; D004357:Drug Synergism; D013006:Growth Hormone / Q000494:pharmacology*; D018969:Insulin-Like Growth Factor Binding Proteins / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D007985:Leydig Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors; D013002:Somatomedins / Q000494:pharmacology*; D013739:Testosterone / Q000378:metabolism
D000728:Androgens; D018969:Insulin-Like Growth Factor Binding Proteins; D007375:Interleukin-1; D013002:Somatomedins; D013196:Dihydrotestosterone; D013739:Testosterone; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D013006:Growth Hormone; D017526:Receptor, IGF Type 1