Inhibitory actions of interleukin-1β on steroidogenesis in primary cultures of neonatal rat testicular cells

Abstract

Abstract. Interleukin-1 is an important cytokine produced by activated macrophages. Because macrophages have been localized in the testis and interleukin-1 bioactivity has been observed in the testis, the potential effect of interleukin-1 on gonadotropin-stimulated androgen production was investigated using primary cultures of neonatal rat testis cells. Cells were incubated for 3 days before change of medium and treatment with human chorionic gonadotropin and interleukin-1. After 3 additional days medium testosterone and progesterone levels were determined. Human chorionic gonadotropin treatment (0.30–30 μg/l) of cultured cells stimulated testosterone production dose-dependently with a maximum increase > 18-fold over control values. Although interleukin-1 treatment alone did not affect testosterone production, the concomitant addition of interleukin-1 β (0.5–5 × 103 U/l) caused a dose-dependent decrease of human chorionic gonadotropin action, with 50% inhibition occurring at 1.4 × 103 U/l (0.6 × 10−11 mol/l; N = 5 experiments). Interleukin-1β also inhibited forskolin- and dibutyryl cAMP-stimulated testosterone production. The suppression of human chorionic gonadotropin-induced testosterone production by testis cells was accompanied by increased (>3-fold) progesterone levels. Moreover, the conversion of exogenously added androgen precursors (progesterone and 17α-hydroxyprogesterone) to testosterone by human chorionic gonadotropin-stimulated cells was suppressed by interleukin-1β suggesting that the activity of the 17α-hydroxylase enzyme may be decreased. The present study shows that interleukin-1β is a potent inhibitor of androgen biosynthesis by rat testiscular cells in culture and it can be hypothesized that this cytokine may play intratesticular paracrine roles.