Interleukin-1 alpha as a potent inhibitor of gonadotropin action in porcine Leydig cells: site(s) of action.
The effects of interleukin on testicular steroidogenesis have been studied in several laboratories, most often by using cultured rat Leydig cells. Several reports have indicated that interleukin-1 beta (IL-1 beta), but not interleukin-1 alpha (IL-1 alpha), exert a potent effect on gonadotropin action in rat Leydig cells. By using cultured porcine Leydig cells as a model, we found that IL-1 alpha (and to a lesser extent IL-1 beta), contrary to previous reports, is a potent inhibitor of LH/hCG steroidogenic action; and we further localized the steroidogenic biochemical step(s) affected by IL-1 alpha. IL-1 alpha inhibited hCG-induced testosterone secretion (about 67%) in a dose- and time-dependent manner. Half maximal and maximal effects were obtained with 4 U/ml (approximately 0.4 ng/ml, 0.3 x 10(-10) M) and 20 U/ml (approximately 2 ng/ml, 1.4 x 10(-10) M) of IL-1 alpha, respectively. The inhibitory effect of IL-1 alpha on gonadotropin action was detected at 6 h and was maximal after 24 h of treatment with the cytokine. The IL-1 alpha inhibitory effect was more potent than that of IL-1 beta: the maximal inhibitory effect of IL-1 beta was obtained with 400 U/ml. Subsequent investigations indicated that IL-1 alpha inhibited different biochemical steps involved in gonadotropin-induced testicular steroidogenesis. In this context, although IL-1 alpha appears to inhibit Leydig cell membrane functions (through a decrease in LH/hCG binding and gonadotropin-induced cAMP production), the antigonadotropin action of the cytokine is probably exerted predominantly at a step(s) located beyond cAMP formation.(ABSTRACT TRUNCATED AT 250 WORDS)
Mauduit
C
C
INSERM CJF n. 90-08, Laboratoire de Biochimie Hôpital Sainte Eugénie, Lyon, France.
Chauvin
M A
MA
Hartmann
D J
DJ
Revol
A
A
Morera
A M
AM
Benahmed
M
M
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000502:physiology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D006888:Hydroxycholesterols / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D007985:Leydig Cells / Q000187:drug effects / Q000378:metabolism*; D007986:Luteinizing Hormone / Q000494:pharmacology*; D008297:Male; D013552:Swine; D013739:Testosterone / Q000096:biosynthesis* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D006063:Chorionic Gonadotropin; D006888:Hydroxycholesterols; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; C003585:22-hydroxycholesterol; D015124:8-Bromo Cyclic Adenosine Monophosphate; D013739:Testosterone; D004815:Epidermal Growth Factor; D007986:Luteinizing Hormone; D000242:Cyclic AMP