Effects and interactions of prostaglandin F2 alpha, oxytocin, and cytokines on steroidogenesis of porcine luteal cells.

Abstract

In the porcine corpora lutea (CL), prostaglandin F2 alpha (PGF2 alpha) and oxytocin (OXT) inhibit progesterone (P) but stimulate estradiol (E2) secretion from luteal cells kept under primary culture conditions. In vivo, both compounds are reported to have luteolytic properties when administered during the late luteal phase; in young CL, however, both substances stimulate P secretion, an effect which is E2-mediated. During the late luteal phase luteal cells appear to produce cytokines, and in addition, cytokine-producing macrophages invade the CL. We tested therefore whether cytokines, particularly tumor necrosis factor-alpha (TNF), have effects on basal or human CG-stimulated steroidogenesis. Furthermore, the interactions of cytokines with PGF2 alpha and/or OXT were investigated. TNF, and less potently interleukin (IL)-1 and IL-2 but not IL-6, inhibited basal as well as human CG-stimulated release of P and E2 in both small and large luteal cells. The inhibiting effect of PGF2 alpha and OXT on P secretion was augmented by these active cytokines. The stimulatory effect of PGF2 alpha and OXT on small and large luteal cell E2 production was completely inhibited. A profound stimulatory effect of E2 and small luteal cell P secretion was completely prevented by the cytokines, with TNF being more potent than IL-1 or -2. We conclude that the cytokines, particularly TNF, have luteolytic functions by their direct inhibiting effects on luteal cell P production. In addition, the cytokines inhibit synthesis and action of PGF2 alpha- and OXT-stimulated E2 secretion. Since E2 is a potent stimulator of luteal cell P production, this luteotropic signal is eliminated by cytokines, which add to the process of luteolysis.

Expression of factors associated with apoptosis in the porcine corpus luteum throughout the luteal phase of the estrous cycle and early pregnancy: Their possible involvement in acquisition of luteolytic sensitivity

“…Macrophages infiltrating porcine CL during the midluteal phase [31] produce TNFa, a cytokine possessing a wide repertoire of physiological functions in the ovary of various animal species [32], including pigs [33]. The present results confirm the expression of TNFa in CL of cyclic and pregnant pigs as previously reported [34].…”

“…The discrepancy between mRNA and protein levels may have resulted from posttranscriptional modification. Nevertheless, the increase of TNFa observed in the present study at the late luteal phase could be the necessary step in sensitization of porcine CL to further luteolytic action of PGF2a, as reported previously in both in vitro [33] and in vivo studies [35]. Interestingly, increased content of TNFa was The luteal (ng/g of luteal tissue; A) and blood plasma progesterone (P 4 ; pg/mL; B) concentrations throughout the luteal phase of the estrous cycle and the corresponding days of early pregnancy.…”

Effects of Interleukin-6 on Proliferation and Follicle-Stimulating Hormone-Induced Estradiol Production by Bovine Granulosa Cells in Vitro: Dependence on Size of Follicle1

“…In contrast, others have observed no significant effect of IL-2 or IL-3 on FSH-induced estradiol production by cultured rat granulosa cells [26]. In comparison, no significant effect of IL-6 was observed on basal or hCG-induced progesterone or estradiol production by porcine luteal cells [30] whereas IL-1 was found to inhibit hCG-induced estradiol production by both porcine [30] and human [29,31] luteal cells. Also, IL-1 inhibited hCG-induced androsterone production by rat whole ovarian dispersates whereas IL-2 and IL-6 had no effect [32].…”

Possible Role of Interleukin-1 in the Regulation of Bovine Corpus Luteum Throughout the Luteal Phase1

“…This should be taken into consideration for future studies in IL-1 effects on P 4 production using a cell culture system. PGF 2␣ functions not only as a luteolytic factor [21,[29][30][31] but also as a luteotropic factor [16][17][18], whereas PGE 2 functions mainly as a luteotropic factor [32,33]. Therefore, the ratio of PGE 2 and PGF 2␣ secretion may be more interesting than the absolute amounts of each PG.…”

“…These results imply that IL-1␣ and IL-1␤ function as luteotropic factors by stimulating luteal PG production in the bovine CL. In addition, IL-1 has been reported to inhibit basal and gonadotropin-stimulated P 4 from luteal cells of pigs [21] and cattle [12]. These findings suggest that IL-1␣ and IL-1␤ act not only as luteotropic, but also as luteolytic mediators in cattle.…”