Modulation of Bovine Luteal Cell Synthetic Capacity by Interferon-γ1

Abstract

Previous work from our laboratory has demonstrated that major histocompatibility complex (MHC) antigens are expressed on cultured bovine luteal cells following exposure to the T lymphocyte-derived cytokine, interferon-gamma (IFN-gamma). In light of these actions of IFN-gamma, it was of interest to investigate the effects of this cytokine on other aspects of luteal function. Therefore, bovine luteal cells were cultured for 7 days in the presence or absence of IFN-gamma, and luteal progesterone (P4), prostaglandin F2 alpha (PGF2 alpha), and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) production were evaluated. After a 24-h exposure to IFN-gamma (100 U), both PGF2 alpha and 6-keto-PGF1 alpha production were decreased approximately 50% (p less than 0.05). However, as time in culture progressed, IFN-gamma markedly increased the synthesis of both prostaglandins approximately 400% above controls (p less than 0.05). Stimulation of prostaglandin production by IFN-gamma was abrogated by the addition of exogenous P4. During the period of IFN-gamma-stimulated prostaglandin synthesis, LH-stimulated P4 production was inhibited by IFN-gamma treatment. However, the suppression of P4 production by IFN-gamma was not mediated by the increase in prostaglandins since concomitant treatment with indomethacin did not reverse the inhibition of steroidogenesis. These results suggest that IFN-gamma, in addition to an indirect role in promoting immune response mechanisms, may also directly affect luteal function by enhancing luteal prostaglandin synthesis and by inhibiting luteal steroidogenesis.

Expressions of Estrogen Receptors in the Bovine Corpus Luteum: Cyclic Changes and Effects of Prostaglandin F2.ALPHA. and Cytokines

“…The doses of TNFα (1.45 nM) and IFNγ (1.25 nM) used in the present study did not affect cell viability (data not shown), although we have previously demonstrated that higher concentrations of TNFα and IFNγ have cytotoxic effects on bovine luteal cells [24]. TNFα and IFNγ are present in the bovine CL throughout the luteal phase [37,39] and are potent stimulators of luteal PGF2α production [37,38,40]. Since PGF2α stimulates progesterone production in the bovine CL in vitro [31], we suggest that TNFα and IFNγ act as luteotropic agents at the concentration used in the present study.…”

Acid sphingomyelinase involvement in tumor necrosis factor α-regulated vascular and steroid disruption during luteolysis in vivo

“…It is generally accepted that cytokines serve a significant role in PGF-induced luteal regression because they are capable of disrupting steroidogenesis (20)(21)(22)(23) and stimulating apoptosis of MVECs (24,25) and steroidogenic luteal cells (26,27). Each of the cell types within the CL has the capacity to respond differently to various cytokines (18).…”

Fas Antigen-Mediated Apoptosis of Ovarian Surface Epithelial Cells*

“…It is not known whether IFN is a physiological trigger for Fas antigen expression in the ovary or whether another factor(s) might regulate Fas antigen expression and/or responsiveness. However, IFN has been shown to have other effects on ovarian function, including inhibition of LH receptor induction (31), gonadotropin-stimulated steroidogenesis (31)(32)(33)(34), and inhibin production (34) by granulosa cells and inhibition of progesterone secretion by bovine luteal cells (35). Infiltration by leukocytes occurs as part of the normal physiology of the ovary (36), and these cells could provide a source of IFN; T lymphocytes and IFN were found in the follicular fluid of human ovaries (37,38).…”