Interleukin-2 is a potent inhibitor of Leydig cell steroidogenesis.
Interstitial tissue of the testis consists of Leydig cells, macrophages, lymphocytes, plasma cells, mast cells and fibroblasts. Previously we have reported that interleukin-1 (IL-1) inhibits Leydig cell androgen production. In the present study, the effect of IL-2 was investigated. Leydig cells (10(5) cells/ml) from adult Sprague-Dawley rats were cultured with or without IL-2 for 24 h. After medium changes, human CG (hCG), 8-bromo-cAMP, or forskolin was added with or without IL-2. Cultures were continued for an additional 24 h, and testosterone and cAMP levels were measured. IL-2 up to 100 U/ml had no effect on basal testosterone production. hCG-stimulated testosterone formation was inhibited in a dose-dependent manner by the addition of IL-2. IL-2 in a concentration of 100 U/ml decreased hCG-induced testosterone formation from 49.6 +/- 3.6 ng/ml (mean +/- SE) to 8.5 +/- 4.2 ng/ml. The hCG dose-response curve was shifted to the right by the addition of IL-2. Maximal testosterone production in response to hCG was reduced 40% in the presence of IL-2 (50 U/ml) without alteration of median effective dose (ED50). IL-2 also inhibited hCG-induced cAMP formation and 8-bromo cAMP- and forskolin-stimulated testosterone production. However, IL-2 did not alter the binding of [125I]hCG to purified Leydig cells. Furthermore, IL-2 significantly inhibited the conversion of 20-OH-cholesterol, 22-OH-cholesterol, pregnenolone, progesterone, 17 alpha-hydroxypregnenolone, and 17 alpha-hydroxyprogesterone to testosterone but did not alter the conversion of dehydroepiandrosterone and androstenedione to testosterone. Our results suggest that a T cell growth factor, IL-2, is a potent inhibitor of steroidogenesis. IL-2 may play a paracrine role in modulating Leydig cell function.
Guo
H
H
Medical Service, WJB Dorn Veterans' Hospital, Columbia, South Carolina 29201.
Calkins
J H
JH
Sigel
M M
MM
Lin
T
T
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D006063:Chorionic Gonadotropin / Q000378:metabolism / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis; D006888:Hydroxycholesterols / Q000378:metabolism; D007376:Interleukin-2 / Q000494:pharmacology*; D007985:Leydig Cells / Q000378:metabolism*; D008297:Male; D011284:Pregnenolone / Q000378:metabolism; D011374:Progesterone / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000494:pharmacology; D013739:Testosterone / Q000096:biosynthesis*
D006063:Chorionic Gonadotropin; D006888:Hydroxycholesterols; D007376:Interleukin-2; D011994:Recombinant Proteins; C003585:22-hydroxycholesterol; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D013739:Testosterone; D011374:Progesterone; C025813:20-hydroxycholesterol; D011284:Pregnenolone; D000242:Cyclic AMP