The rat intraovarian interleukin (IL)-1 system: cellular localization, cyclic variation and hormonal regulation of IL-1 beta and of the type I and type IIIL-1 receptors

An increasing body of evidence supports the possibility that intraovarian i nterleukin (IL)-1 plays an intermediary role in the perovulatory cascade. T o gain further insight into the intraovarian IL-1 hypothesis, we studied th e cellular localization cyclic variation and hormonal regulation of IL-1 be ta, as well as of the type I and type II IL-1 receptors (IL-1R) in immature rats. In situ hybridization localized IL-I beta and type I IL-1R transcrip ts to the granulosa cell compartment, the innermost layers of the theca int erna and to the oocyte of the untreated immature ovary. Molecular probing o f whole ovarian material in the course of a simulated estrous cycle reveale d a progressive preovulatory increase in IL-1 beta and type I IL-1R transcr ipts to an in vivo peak at the time of ovulation (3.0- and 2.5-fold increas es over untreated controls; P < 0.05). Comparable efforts to localize and p robe for type II IL-1R transcripts failed to elicit a detectable signal. Th e basal in vitro expression pattern of IL-1 beta and type II IL-IR transcri pts by whole ovarian dispersates revealed an early (4 h) spontaneous increa se to a peak (2.1- and 5.8-fold increases over time 0; P < 0.05) followed b y a gradual decline to a 48 h nadir. Treatment of whole ovarian dispersates with the IL-1 receptor antagonist (IL-1RA) or with IL-1 beta failed to alt er the initial (4 h) burst of IL-IP or of type II IL-1R expression thereby suggesting IL-1-independence. Treatment with hCG proved equally ineffective . However, longer-term treatment of whole ovarian dispersates with IL-1 bet a produced a significant secondary increase (5.9-fold over time 0; P < 0.05 ) in IL-IP (but not type II IL-1R) transcripts by 48 h. This IL-1 effect wa s completely blocked by co-treatment with IL-1RA thereby suggesting mediati on via a specific IL-1 receptor. Qualitatively comparable but quantitativel y reduced results obtained for isolated granulosa cells. The basal in vitro expression pattern of type I IL-IR transcripts by whole ovarian dispersate s revealed a progressive spontaneous increase (3.1-fold increase overall) o ver the 48 h culture. Treatment with IL-1 beta produced a significant (P < 0.05) increase (5-fold) in type I IL-1R transcripts by 48 h, an effect whic h was completely blocked by co-treatment with IL-IRA. Taken together, these observations: (1) localize IL-IP and its type I receptor to granulosa cell s, the innermost layers of the theca interna and to the oocyte; (2) confirm their periovulatory in vivo expression pattern; (3) document their express ion by untreated cultured whole ovarian dispersates; and (4) demonstrate th eir in vitro responsiveness to receptor-mediated/IL-1-driven autocrine ampl ification. The type II IL-1R was undetectable in vivo, its in vitro express ion pattern proving IL-1- and hCG-independent. The periovulatory expression pattern of IL-1 beta and its receptor (type I) is compatible with the noti on that the intraovarian IL-I system may play an intermediary role in the o vulatory process. (C) 1999 Published by Elsevier Science Ireland Ltd. All r ights reserved.