Inhibition by gonadotropins of interleukin-1 production by rabbit granulosa and theca cells: effects on gonadotropin-induced progesterone production

Abstract

Increasing evidence suggests that cytokines may play a role in ovarian processes. The purpose of this study was to determine if interleukin-1 (IL-1) could modulate rabbit pre-ovulatory follicular function and to explore cellular sites of IL-1 biosynthesis in rabbit follicles. Development of rabbit pre-ovulatory follicles was induced by 200 mIU equine chorionic gonadotropin daily for 2 days. Seventy-two hours after the last injection, ovaries were excised and granulosa and theca cells isolated. The two types of cell were pre-incubated for 24 h in Minimum Essential Medium (MEM) with 5% fetal calf serum (FCS), and then incubated for 24 h in MEM with 2.5% FCS with appropriate stimulants. Results showed that rabbit granulosa and theca cell culture supernatants contain IL-1 bioactivity and that this bioactivity was diminished by gonadotropins, FSH and human chorionic gonadotropin, in a dose-dependent manner. Low doses of IL-1 (1 ng/ml) inhibited gonadotropin-induced progesterone production in both cell types and at the same time increased cell numbers. A study of the mechanism of IL-1 action demonstrated that it affects cAMP generation, and also steps distal to cAMP formation. We conclude that in our model gonadotropins, by inhibiting IL-1 production, could control IL-1 modulation of gonadotropin action on steroidogenesis.

Rabbit ovarian production of interleukin-6 and its potential effects on gonadotropin-induced progesterone secretion in granulosa and theca cells

“…1988, Santana et al 1996. However, in the present study, we could not document an inhibition by IL-6 of the FSH-induced cAMP accumulation (unpublished data), because, as previously reported (Bréard et al 1998), the dose of FSH used was unable to stimulate granulosa cAMP accumulation, although this gonadotropin concentration stimulated 15-fold the basal progesterone production (an apparent discrepancy which has been largely reported in the past (Azhar & Menon 1979)). However, the precAMP defect could be localized by the use of cholera toxin.…”

“…Moreover, Machelon et al (1994a) working on human granulosa cells demonstrated that levels of IL-6 transcripts were similar in preparations treated to remove immune cells and in untreated ones, and concluded that IL-6 biosynthesis by macrophages was a negligible source of IL-6. Taken together, these observations seem to exclude the possibility that cytokine bioactivity detected in supernatants of cell cultures in our study could originate from white blood cells (Bréard et al 1998).…”

“…This latter effect was apparently predominant when an intracellular cAMP rise was induced by FSH, since only the inhibitory effect was observed. Such antagonistic pre-and post-cAMP effects were previously observed when studying the role of IL-1 in the rabbit (Bréard et al 1998) as well as in other species (Gottschall Table 2 Effect of IL-6 on progesterone production by theca cells induced by Db-cAMP (1 mM) or forskolin (1 µg/ml). 1988, Santana et al 1996.…”

“…We previously observed that estradiol was released in response to FSH and hCG by cultured granulosa and theca cells respectively (Féral et al 1995) and estradiol has been shown to inhibit the ovarian IL-6 expression (Pottratz et al 1994). Moreover, IL-1 stimulated IL-6 production and we previously reported that, in the rabbit, IL-1 bioactivity production in cultured granulosa and theca cell supernatants was inhibited by gonadotropins (Bréard et al 1998). So we can assume that gonadotropins could inhibit IL-6 release at least in part through both an increase in estradiol production and a decrease in IL-1 production.…”

High doses of dietary zinc induce cytokines, chemokines, and apoptosis in reproductive tissues during regression

“…In our earlier studies, we have noticed a reduction of estrogen and progesterone in birds stimulated to molt by high doses of zinc (Anish et al 2007). In mammals, proinflammatory cytokines have been found to inhibit ovarian steroidogenesis by inhibiting the gonadotropin-support (Bornstein et al 2004;Breard et al 1998aBreard et al , 1998bHurwitz et al 1991;Best and Hill 1995;Yasuda et al 1990;Young et al 1997). Therefore, the effect of zinc on ovarian steroids might be mediated through cytokines.…”