Human intraovarian interleukin-1 (IL-1) system: highly compartmentalized and hormonally dependent regulation of the genes encoding IL-1, its receptor, and its receptor antagonist.

Abstract

To delineate the scope of the human intraovarian IL-1 system we used a solution hybridization/RNase protection assay to test for expression of the genes encoding IL-1, its type I receptor (IL-iR), and its receptor antagonist (IL-iRA). IL-1 transcripts were not detected in whole ovarian material from days 4 or 12 of an unstimulated menstrual cycle but transcripts (IL-i10 >> IL-lla) were detected in preovulatory follicular aspirates from gonadotropin-stimulated cycles. Concurrently obtained peripheral monocytes did not contain IL-1,6 transcripts but macrophage-depleted follicular aspirates did, thus implicating the granulosa cells as the site of IL-1 expression. IL-iR transcripts were detected in RNA from whole ovaries and follicular aspirates but not in RNA from peripheral monocytes. IL-iRA transcripts were detected in whole ovarian material as well as in macrophage-free follicular aspirates. Cultured human granulosa and theca cells did not contain mRNA for IL-1,B or IL-iRA but did contain mRNA for IL-1R. Treatment of cell cultures with forskolin (25 ,uM) induced IL-i#t transcripts in granulosa but not theca cells. Forskolin also increased the basal levels of IL-iR transcripts in both granulosa and theca cells but did not induce IL-RA transcripts in either cell type. Taken together, these findings reveal the existence of a complete, highly compartmentalized, hormonally dependent intraovarian IL-1 system replete with ligands, receptor, and receptor antagonist. (J.

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

“…It is likely that macrophages act as a source of intraovarian IL-1 (5). On the other hand, it has been reported that in the rat theca-interstitial cells are sites of IL-1b gene expression (5), and that cultured human granulosa cells produce IL-1b (6,7).…”

The midcycle increase in ovarian glucose uptake is associated with enhanced expression of glucose transporter 3. Possible role for interleukin-1, a putative intermediary in the ovulatory process.

“…Second, the addition of an IL-1 receptor antagonist has been shown to attenuate LH-supported ovulation under both ex vivo (4) and in vivo (5) circumstances. Third, some components of the intraovarian IL-1 system (e.g., IL-1 ␤ and the type I IL-1 receptor) appear to be expressed in vivo, mainly during a narrow periovulatory window (6)(7)(8)(9)(10)(11)(12). Fourth, IL-1 ␤ has been shown to induce a host of ovulation-associated phenomena in vitro, such as the promotion of prostaglandin production (13)(14)(15)(16), the stimulation of hyaluronic acid biosynthesis (17), the induction of collagenase activity (18), and the activation of nitric oxide synthase activity (19)(20)(21).…”

Nitric oxide mediates interleukin-1-induced cellular cytotoxicity in the rat ovary. A potential role for nitric oxide in the ovulatory process.

“…Indeed, recent studies have pointed to the macrophage and its secretory products as potential in situ regulators of ovarian function (2). Specifically, IL-1-like activity has been demonstrated in follicular fluid (3,4), and it appears that acquisition of intraovarian IL-1 synthetic capacity is gonadotropin dependent (2), pointing to an intermediary role for IL-1 in the ovulatory cascade.…”

“…Indeed, recent studies have pointed to the macrophage and its secretory products as potential in situ regulators of ovarian function (2). Specifically, IL-1-like activity has been demonstrated in follicular fluid (3,4), and it appears that acquisition of intraovarian IL-1 synthetic capacity is gonadotropin dependent (2), pointing to an intermediary role for IL-1 in the ovulatory cascade. The perception that this cascade involves tissue remodeling and cell death, along with the observation that treatment of primary rat ovarian cell cultures with IL-1 pro-duces marked time-dependent morphologic changes, including irreversible detachment and cell death (5 ), places IL-1 and the macrophage at the center of an incompletely described intraovarian network regulating follicular development and rupture.…”