OVARIAN EXPRESSION, CELLULAR-LOCALIZATION, AND HORMONAL-REGULATION OFRAT SECRETORY PHOSPHOLIPASE A(2) - INCREASED EXPRESSION BY INTERLEUKIN-1 AND BY GONADOTROPINS

It has been suggested that ovulation may constitute a cyclic inflammat ory-like process and that gonadotropin-inducible intraovarian interleu kin (IL)-1, an established mediator of inflammation, may play a centra l role in this regard. In support of this hypothesis, our group has be en able to document the ability of IL-1 to potently stimulate prostagl andin biosynthesis by cultured rat ovarian cells. Herein we explore th e possibility that the prostaglandin-stimulating action of IL-1 is due , in part, to the enhanced expression of ovarian secretory phospholipa se-A(2) (sPLA(2)). A single sPLA(2) transcript of 1.4 kilobases was no ted in all extraovarian tissues of immature rat origin subjected to No rthern blot analysis. However, only a barely detectable signal was app arent in ovarian tissue. In contrast, the more sensitive RNase protect ion assay revealed the unequivocal presence of ovarian sPLA, transcrip ts. Cellular localization studies by way of in situ hybridization docu mented sPLA(2) transcripts primarily in the granulosa cell of the peri ovulatory ovary. Molecular probing of untreated cultured whole ovarian dispersates disclosed spontaneous elaboration of sPLA(2) transcripts as early as 20 h after the introduction of cells into culture. Treatme nt of cultured whole ovarian dispersates with IL-1 beta for 48 h produ ced a 1.7-fold increase (over the value in untreated controls) in the relative expression of sPLA(2) transcripts (p < 0.01) along with a 1.7 -fold increase in media PLA(2) activity (p < 0.01). A more marked incr ease was documented for IL-1 beta-treated cultured isolated granulosa cells (12.5-fold increase, p < 0.001). Treatment of whole ovarian disp ersates with an IL-1 receptor antagonist (IL-1RA) produced a reduction in the basal expression of sPLA(2) transcripts (55% at the 5 mu g/ml dose level; p < 0.01) and PLA(2) activity (40%; p < 0.01), thereby sug gesting basal endogenous IL-1-like bioactivity. Treatment of cultured whole ovarian dispersates with either hCG or FSH led to 2.6-fold (p = 0.056) and 3-fold (p = 0.029) increases in the abundance of sPLA(2) tr anscripts, respectively, effects blocked by the concurrent presence of IL-1RA. These observations 1) document the immature rat ovary as a si te of sPLA(2) gene expression, 2) localize the relevant transcripts to the postovulatory granulosa cell, 3) confirm the presence of function al secreted ovarian PLA(2) activity, 4) reveal PLA(2) expression to be IL-1- and gonadotropin-dependent, and 5) suggest the existence of end ogenous PLA(2)-stimulating IL-1-like activity. These findings also sug gest that the ability of hCG or FSH to up-regulate ovarian sPLA(2) tra nscripts may be due, in part, to the endogenous elaboration of IL-like activity.