Multiple roles of TNF super family members in corpus luteum function

Abstract

The main function of the corpus luteum (CL) is the production of progesterone. Adequate luteal progesterone is crucial for determining the physiological duration of the estrous cycle and for achieving a successful pregnancy. The CL is regulated not only by hypophyseal gonadotropin, but also by a number of cytokines that are locally produced. Tumor necrosis factor-alpha (TNF) and its specific receptors (TNFR) are present in the CL of many species. TNF plays multiple and likely important roles in CL function throughout the estrous cycle. TNF appears to have luteotropic and luteolytic roles in the CLs. In contrast, Fas ligand (Fas L), another member of TNF super family (TNF-SF), is primarily recognized for its apoptotic actions. Presumably, Fas L binds its cognate receptor (Fas) to induce structural luteolysis. This review is designed to focus on recent studies documenting the expression of TNF and Fas L, their receptors, and intracellular signaling mechanisms in the CL.

Figure 1

Possible actions of TNF and Fas L in the luteal cells. TNF and Fas show multiple actions on luteal cell function through complex intracellular pathways. Fig. 1A shows the possible luteolytic actions of TNF and Fas L in the luteal cells. Fig. 1B shows the possible luteotropic actions of TNF in the luteal cells. * Abbreviations; tumor necrosis factor-α (TNF), TNF receptor type I (TNFRI), TNF receptor type II (TNFRII), Fas antigen (Fas), Fas ligand (Fas L), interferon-γ (IFN), insulin-like growth factor-I (IGF), progesterone (P4), P4 receptor (P4-R), mitogen-activated protein kinase (MAPK), phospholipase-A2 (PL-A2), arachidonic acid (AA), nuclear factor-κB (NFκB), jun-n-terminal kinase (JNK).