PARENT SESSION
Corpus Luteum

PROSTAGLANDIN F₂ RAPIDLY INDUCES NEUTROPHIL CHEMOATTRACTANT PROTEIN (CINC/gro) IN RAT CORPORA LUTEA AND LUTEAL CELLS.

Gao, Shiping¹, Preston, Sandra¹, Kayisli, Umit¹, Arici, Aydin¹, Behrman, Harold¹, ¹

ABSTRACT- The functional neutrophil chemoattractant in the rat is referred to as CINC/gro, which is the rat counterpart of human GRO, an interleukin (IL)-8-like chemokine. In the rat, CINC/gro is induced in the theca layer of the preovulatory follicle by gonadotropin as well IL-1 and tumor necrosis factor (TNF). We showed that prostaglandin F₂ induces leukocyte infiltration in the corpus luteum within 2 hours in vivo and this response is associated with an enormous increase in protein kinase C-dependent production of oxygen radicals. Our preliminary cytological studies indicate that neutrophils are the predominant cellular source of this oxygen radical production, but we found leukocytes are refractory to PGF₂. We therefore examined if CINC/gro may be induced by PGF₂ and thereby serve to recruit neutrophils into the corpus luteum. Functional corpora lutea were generated in immature female rats with gonadotropin treatment. In one series of studies, the animals were treated with a luteolytic dose of PGF₂ (0.4mg/Kg) 8 days after ovulation. The ovaries were removed 2 hours after PGF₂ treatment and then examined for the presence of CINC/gro by immunohistochemistry. Very low, but detectable levels of CINC/gro were seen in control corpora lutea, but PGF₂ induced a highly significant and more than 10-fold increase (p<0.001) in CINC/gro expression as determined by morphometry. In another series of studies, luteal cells were isolated 8 days after ovulation and incubated with PGF₂ (1M) for 2, 4 or 18 hours and CINC/gro in media was determined by immunoassay. Media alone showed no detectable CINC/gro. A substantial and near linear secretion of CINC/gro was evident in media of control cells, but PGF₂ increased CINC/gro secretion by about 15% after 18 hours of culture (272 ± 36 versus 313 ± 26 pg/ml/10⁵ cells; p<0.03), a response that was evident within 2 hours of incubation. These findings indicate that PGF₂ stimulates the secretion of CINC/gro by luteal cells, which probably serves an important role in the rapid recruitment of neutrophils in the corpora lutea and the production of oxygen radicals that initiate functional regression. Supported by NIH-HD-10718.

KEY WORDS: oxygen radicals, luteal regression, neutrophils, chemokine