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.
Department of Woman and Child Health, Pediatric Endocrinology Unit, Astrid Lindgren Children's Hospital, Karolinska Institute and Hospital, S-171 76 Stockholm, Sweden.
Eugenia
E
Colón
Konstantin V
KV
Svechnikov
Christine
C
Carlsson-Skwirut
Peter
P
Bang
Olle
O
Soder
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