Gene regulation of interleukin-1 beta, interleukin-1 receptor type I, and plasminogen activator inhibitor-1 and -2 in human granulosa-luteal cells.

OBJECTIVE

To investigate the regulation of messenger ribonucleic acid (mRNA) levels of interleukin-1 beta (IL-1 beta), interleukin-1 (IL-1) receptor type 1, and plasminogen activator (PA) inhibitor-1 and -2 in cumulus cells, granulosa-luteal cells, and macrophage-depleted granulosa-luteal cells obtained from human preovulatory follicles.

DESIGN

Prospective longitudinal study.

SETTING, PATIENTS: Patients undergoing assisted reproductive technologies (ART) in the Department of Gynecology and Obstetrics, Stanford University, Stanford, California.

INTERVENTIONS

Cumulus cells and granulosa-luteal cells were collected by ultrasound-guided transvaginal aspiration at the time of ART.

MAIN OUTCOME MEASURES

Northern blot analysis of mRNA levels of IL-1 beta, IL-1 receptor type 1, PA inhibitor-1 and -2 in cumulus cells, granulosa-luteal cells and macrophage-depleted granulosa-luteal cells, and indirect immunocytochemical analysis of the IL-1 system and macrophages in granulosa-luteal cell preparations were performed.

RESULTS

Interleukin-1 beta mRNA levels in uncultured cumulus cells were less than those of uncultured granulosa-luteal cells with no differences in IL-1 receptor type 1 mRNA levels between these two cell types. Granulosa-luteal cell IL-1 receptor type 1 mRNA levels were expressed constitutively throughout 24 hours of culture with no effect by hCG, whereas IL-1 beta mRNA levels increased within 6 hours, and then remained elevated for 24 hours with no effect by hCG. Interleukin-1 beta significantly increased granulosa-luteal cell mRNA levels of IL-1 beta (over twofold), IL-1 receptor type 1 (over twofold), PA inhibitor-1 (approximately 1.4-fold), and PA inhibitor-2 (approximately 1.6-fold). In contrast, IL-1 beta had no effect on IL-1 beta and IL-1 receptor type 1 mRNA levels in macrophage-depleted granulosa-luteal cells. Granulosa-luteal cells, not macrophages, account for the majority of the immunocytochemical staining for IL-1 beta and IL-1 receptor type 1 in follicular aspirates.

CONCLUSIONS

These studies suggest that the IL-1 system is regulated in human granulosa-luteal cells during the periovulatory period. Furthermore, the augmentation of PA inhibitor-1 and -2 mRNA levels by IL-1 beta suggests a potential role for IL-1 beta in remodeling of the human ovary during the periovulatory period.