Tumor necrosis factor-α (TNFα) inhibits progesterone and estradiol-17β production from cultured granulosa cells: Presence of TNFα receptors in bovine granulosa and theca cells

Ryosuke Sakumoto, Masami Shibaya, Kiyoshi Okuda

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The aim of this study was to investigate whether functional tumor necrosis factor-α (TNFα) receptors are present in the granulosa cells and the cells of theca interna (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 ovary and the uterus (size, color, consistency and mucus), and the ratio of progesterone (P4) and estradiol-17β (E2) 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, TNFα 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 TNFα (rhTNFα; 0.06-6 nM) inhibited E2 secretion in a dose-dependent fashion (P<0.01), but did not affect P4 secretion. In addition, rhTNFα inhibited follicle stimulating hormone-, forskolin- or dibutylyl cyclic AMP-induced P4 and E2 secretion by the cells (P<0.01). These results indicate the presence of functional TNFα receptors in bovine granulosa and theca cells in small, preovulatory and atretic follicles, and suggest that TNFα plays a role in regulating their secretory function.

Original languageEnglish
Pages (from-to)441-449
Number of pages9
JournalJournal of Reproduction and Development
Issue number6
Publication statusPublished - Dec 1 2003



  • Bovine
  • Ovary
  • Receptor
  • Tumor necrosis factor-α

ASJC Scopus subject areas

  • Animal Science and Zoology

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