Expression and hormonal regulation of rat ovarian interleukin-1β converting enzyme, a putative apoptotic marker: endocrine- and paracrine-dependence

Abstract

It is the purpose of this paper to assess the expression, cellular localization, and hormonal regulation of rat ovarian interleukin (IL)-1β converting enzyme (ICE), a putative apoptotic marker. In agreement with previous observations ICE transcripts were noted in relatively increased abundance in the thymus, lung, spleen and small intestine. Although ICE transcripts were barely expressed in the untreated, immature rat ovary, they were apparent throughout a simulated estrous cycle. The in vivo expression of ovarian ICE rose gradually from 6 h after ovulation triggering to a peak (1.74-fold increase versus control, P<0.05) 24 h after human chorionic gonadotropin administration, a marked and significant decrease to baseline being noted 24 h later. To examine the effect of in vitro culture on ovarian ICE gene expression, whole ovarian dispersates from immature rats were cultured without treatment for 72 h. ICE gene expression significantly ( P<0.01) increased to a maximum 24 h post plating (2.55-fold increase as compared with time zero). Treatment with IL-1β was associated with a small but statistically insignificant increase in ovarian ICE gene expression. Similarly, provision of IL-RA resulted in a modest, albeit statistically insignificant, decrease in ovarian ICE gene expression. Treatment with GnRH (but not FSH, LH or PMSG) significantly ( P<0.05) increased ovarian ICE gene expression (41.5% increase versus control). Treatment with dexamethasone (but not diethylstilbestrol, R5020 or R1881) produced a significant ( P<0.05) 42.3% decrease in ovarian ICE gene expression as compared with untreated controls. Treatment with TNFα (but not ET-1, TGFα, TGFβ, IGF-I or bFGF) produced a significant ( P<0.01) 2.5-fold increase in ovarian ICE gene expression as compared with untreated controls. Taken together, our present findings: (1) reaffirm the ovarian expression of the ICE gene, (2) document a periovulatory increase in ovarian ICE gene expression, (3) show the inhibitory effect of glucocorticoids in this regard, and (4) establish TNFα as an upregulator. Taken together, these findings suggest a role for ovarian ICE either in the context of apoptosis/atresia or in the context of the ovulatory process.