Interactions between interleukin-1 beta, nitric oxide and prostaglandin E2 in the rat ovary: effects on steroidogenesis

Abstract

It has been reported that interleukin (IL)-1 b induces the synthesis of both nitric oxide (NO) and prostaglandin (PG)E 2 in cultures of dispersed ovarian cells and exerts cytotoxic effects on these cells. Since PGE 2 , NO and IL-1 b have been implicated as modulators of steroidogenesis, experiments have been undertaken to determine how IL-1 b -induced NO and PGE 2 production may affect steroidogenesis in cultures of ovarian dispersates obtained from untreated adult oestrous rats and to compare the action of IL-1 b in cultures of granulosa/luteal (GL) cell-only cultures and GL cells co-cultured with peritoneal macrophages.IL-1 b significantly increased the production of NO (assessed by nitrite measured in the culture medium) and PGE 2 in cultures of ovarian dispersates but had no effect on cultures of GL cells in which NO production was typically very low and PGE 2 production was undetectable. In contrast both NO and PGE 2 were high in co-cultures and were not significantly altered by the addition of IL-1 b . The NO donor sodium nitroprusside inhibited steroidogenesis in cultures of ovarian cells in a dose-dependent manner while PGE 2 had a stimulatory effect. Concomitant inhibition of NO production with aminoguanidine and PG production with indomethacin resulted in a significant enhancement of basal progesterone production in these cultures. Finally, IL-1 b inhibited progesterone responses to forskolin and PGE 2 in ovarian dispersates; an effect not observed in GL cell-only cultures nor in co-cultures in which forskolin-induced progesterone production is always inhibited. No cytotoxic effects of IL-1 b during the 48 h period of culture were observed. A comparison of the steroidogenic NO and PGE 2 responses to IL-1 b in the three culture models suggests that (i) the responses to IL-1 b observed in ovarian dispersates could be due to cytokine activation of resident and infiltrating macrophages or that the action of IL-1 b requires some other heterologous cell-cell contact, and (ii) IL-1 b acts indirectly on signal transduction pathways which stimulate steroidogenesis.

Involvement of inducible nitric oxide synthase in stress-impaired testicular steroidogenesis

“…Thus, it is highly probable that 3 HSD activity is negatively controlled by the stress-activated NO signaling pathway. A similar idea has recently been suggested by others (Ahsan et al 1997).…”

Expression of endothelial nitric oxide synthase in the ovine ovary throughout the estrous cycle

“…In mice, decreased or fully suppressed eNOS expression was associated with reduced ovulation rates (Yamauchi et al 1997, Jablonka-Shariff & Olson 1998. Moreover, it has been suggested that NO upregulates the ovulatory process by stimulation of prostaglandin production and/or through interactions with cytokines (Ahsan et al 1997, Yamauchi et al 1997Rosselli et al 1998, Gregg 2003, Mitchell et al 2004. Based on these observations, we hypothesize that NO regulates ovulatory processes directly by affecting blood vessel function and indirectly by affecting regulatory factors involved in ovulation.…”

Tectorigenin inhibits IFN-γ/LPS-induced inflammatory responses in murine macrophage RAW 264.7 cells

“…Moreover, IL-1 consistently induces COX-2 gene expression and PGE 2 synthesis in several cell lines and in primary human blood monocytes (Dinarello and Thompson 1991;Reznikov et al, 2000). In addition, IL-1β stimulated NO release and iNOS expression (Ahsan et al, 1997;Ellman et al, 1993). Taken together, IL-1β has powerful activity in the inflammation and therefore specific inhibition activity of tectorigenin on IL-1β production, not on TNF-α production, was considered as an important meaning in medicinal food.…”