Effects of Cytokines on Porcine Granulosa Cell Steroidogenesis in Vitro1

Abstract

Recent evidence indicates that factors produced by immune cells (cytokines) may play a role in ovarian function. To explore this possibility, we examined the effects of conditioned medium obtained from cultures of either unstimulated splenocytes (splenocyte-conditioned medium; SCM) or concanavalin A-stimulated splenocytes (CAS) on estrogen and progesterone production by porcine granulosa cells. Granulosa cells were obtained from small (less than 3 mm) or large (greater than 7 mm) follicles and treated with increasing doses of SCM or CAS in the presence or absence of pFSH (100 ng/ml) for 24 h at 37 degrees C. In granulosa cells obtained from small follicles it was found that both SCM and CAS evoked a dose-dependent increase in estrogen but not progesterone production. Estrogen production was no further enhanced by the presence of FSH. Additionally, SCM was able to augment FSH-stimulated progesterone production by these cells, whereas CAS had no effect. Identical treatment of granulosa cells obtained from large follicles demonstrated that both SCM and CAS caused dose-dependent increases in estrogen as well as progesterone production. In response to CAS, FSH augmented progesterone production but exerted a biphasic on estrogen production (inhibiting at lower doses while stimulating at higher doses). In contrast, SCM had no effect on FSH-stimulated estrogen production. Additional controls indicated that the above results could not be attributed to either concanavalin A or serum. Taken together, these findings suggest that cytokines can exert significant effects over granulosa cell steroidogenesis and further imply that these factors may play an important role in the differentiation and developmental regulation of granulosa cell function.

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

“…Our studies also indicate that the granulosa cell responsiveness to cytokines is dependent on size of follicle. Similarly, previous studies have indicated that the response of granulosa cells from small porcine follicles to conditioned medium from cultured splenocytes (a source of cytokines) is different from that of granulosa cells from large porcine follicles [16]. Why granulosa cells from large bovine follicles are 40 times less sensitive to IL-6 than granulosa cells from small bovine follicles is uncertain.…”

“…Other potential sources of cytokines within the ovary include the CL [12,13] and various immune cells [14,15]. Whether cytokines differentially affect granulosa cell functions in small and large follicles is unknown, although a recent study indicates that granulosa cells from small and large follicles respond differently to conditioned medium from cultured splenocytes (a source of cytokines) [16]. Also, reports on direct effects of cytokines on aromatase activity of bovine ovarian cells are meager.…”

Effects of the thymic peptide thymulin on in vitro and in vivo testicular steroid concentrations in white composite and Meishan boars.

“…Functions of immuno-peptides outside of the regulatory and control aspects on the immune system are now being elucidated (Adashi, 1990;Pollanen et al, 1990). Secretory products from media of macrophage, splenic, and thymic cell cultures can stimulate (Yee and Hutson, 1985;Gorospe and Kasson, 1988;Hughes et al, 1990;Uzumcu and Lin, 1994) or inhibit ovarian and testicular steroidogenesis (Aguilera and Romano, 1989;Reyes-Esparza and Romano, 1989;Watson et al, 1994). Within the testis reside numerous immune cells (Hermo and Lalli, 1978;Pollanen and Maddocks, 1988;Setchell et al, 1990;Bergh et al, 1993;Gaytan et al, 1994;Pinilla et al, 1994;Wang et al, 1994), and the potential for local immunoregulation of testicular function is under evaluation Skinner, 1991;Hutson, 1992;Gaytan et al, 1996).…”

The Shifting Role and Regulation of the Corpus Luteum in Vertebrate Reproduction: A Synthetic Review

“…The luteotrophic and luteolytic nature of immune factors depends on the luteal environment, particularly on the absence of immunosuppressive factors such as progesterone (Walusimbi and Pate 2013). Macrophages likely play a crucial role in the resolution of the luteolytic process and avoidance of an inflammatory response (Pate and Keyes 2001), whereas T lymphocytes enhance progesterone production in the CL of several species(Emi et al 1991, Hughes et al 1990. On the other hand, progesterone inhibits lymphocyte proliferation and interferes with the cytokine action on the luteal cells (reviewed bySiiteri and Stities 1982, Grossmanm 1984, Kelly 1994).…”