Interleukin-1 inhibits Leydig cell steroidogenesis in primary culture.
Inflammation and infection induce an acute phase response. The response is characterized by fever and production of interleukin-1 (IL-1). In the present study we evaluated the effects of interleukin-1 on Leydig cell function in primary culture. hCG-stimulated testosterone formation was markedly reduced by IL-1, with an ED50 of 1 U/ml. Basal testosterone production was slightly enhanced in the presence of low concentrations of IL-1, while high concentrations of IL-1 inhibited testosterone formation. Significant inhibition of hCG-stimulated testosterone formation was noted as early as 8 h after the addition of IL-1. IL-1 also inhibited hCG-stimulated cAMP formation, as well as 8-bromo-cAMP- and forskolin-stimulated testosterone synthesis. Furthermore, LH binding to Leydig cells was reduced by human IL-1. The inhibitory effects of IL-1 were reversed only partially by the addition of a cyclooxygenase inhibitor, indomethacin (0.1 mM), even though prostaglandin E2 formation was completely blocked. This indicates that the observed effects of IL-1 are not completely mediated by increased PGE2 formation. The present study suggests that IL-1 is a potent modulator of Leydig cell steroidogenesis. Decreased testosterone formation may modulate the immune response and contribute to the catabolic changes occurring during infection.
Calkins
J H
JH
Medical Service, W.J.B. Dorn Veterans Hospital, Columbia, South Carolina 29201.
Sigel
M M
MM
Nankin
H R
HR
Lin
T
T
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D015232:Dinoprostone; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D007700:Kinetics; D007985:Leydig Cells / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D011458:Prostaglandins E / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D011974:Receptors, LH / Q000378:metabolism; D013739:Testosterone / Q000096:biosynthesis*
D006063:Chorionic Gonadotropin; D007375:Interleukin-1; D011458:Prostaglandins E; D011974:Receptors, LH; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D013739:Testosterone; D015232:Dinoprostone; D007213:Indomethacin