Tumor necrosis factor-alpha (TNFalpha) inhibits progesterone and estradiol-17 beta production from cultured granulosa cells: Presence of TNFalpha receptors in bovine granulosa and theca cells
2003
Sakumoto, R. (Okayama Univ. (Japan)) | Shibaya, M. | Okuda, K.
Abstract. The aim of this study was to investigate whether functional tumor necrosis factor-a (TNFa) receptors are present in the granulosa cells and the cells of theca intena (theca cells), obtained from bovine follicles classified into one of three groups. Each group was defined as either small vesicular ovarian follicles (small follicles; 3-5 mm in diameter), preovulatory mature ovarian follicles (preovulatory follicles) or atretic follicles (12-18 mm) according to gross examination of the corpus luteum in the epsilateral or contralateral 6vary and the uterus (size, color, consistency and mucus), and the ratio of progesterone (P sub 4) and estradiol-17v(E sub 2) concentrations in follicular fluid. A Scatchard analysis showed the presence of a high-affinity binding site on both granulosa and theca cells from all follicles examined (dissociation constant: 4.7 =+- 0.15 to 6.9 =+- 1.40 nM). Moreover, TNFa receptor concentrations in granulosa and theca cells obtained from atretic follicles were significantly higher than those in the cells from preovulatory follicles (P<0.05). Exposure of cultured granulosa cells from small antral follicles to recombinant human TNFa (rhTNFa; 0.06-6 nM) inhibited E sub 2 secretion in a dose-dependent fashion (P<0.01), but did not affect P sub 4 secretion. In addition, rhTNFa inhibited follicle stimulating hormone-, forskolin- or dibutylyl cyclic AMP-induced P sub 4 and E sub 2 secretion by the cells (P<0.01). These results indicate the presence of functional TNFa receptors in bovine granulosa and theca cells in small, preovulatory and atretic follicles, and suggest that TNFa plays a role in regulating their secretory function.
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