Granulosa cells as a source and target organ for tumor necrosis factor‐α

Zolti, Mati; Meirom, R.; Shemesh, Mordechai; Wollach, D. R.; Mashiach, Shlomo; Shore, Laurence S.; Rafael, Zion Ben

doi:10.1016/0014-5793(90)80565-z

Cited by 136 publications

(62 citation statements)

References 10 publications

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“…One possible explanation for this pheno menon is t he reduc tion of T NFα receptors. Bioactive TNFα in bovine follicles increased during Days 3 to 20 of the estrous cycle [21], and the expression of TNFα receptors was reduced by TNFα itself [29], so that, as shown in this study, the low levels of TNFα receptor expression in the cells of preovulatory follicles might arise from a local TNFα-mediated reduction.…”

Section: Discussionsupporting

confidence: 64%

“…T h e s e v a l u e s a r e c o m p a r a b l e w i t h t h e characteristics of TNFα receptors in the granulosa cells of pigs [19] and cows [8], and in the corpus luteum of pigs [20] and cows [13]. Previous studies have shown that bovine follicular fluid contains TNFα-like activity, and that the levels of TNFα measured in bovine follicular fluid [21] and serum [22] are comparable with the effective doses of TNFα and the affinity of TNFα receptors described in the present study. Collectively, locally produced TNFα in bovine follicles may act as an autocrine and/or paracrine factor regulating follicular cell function.…”

Section: Discussionmentioning

confidence: 87%

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Tumor Necrosis Factor-.ALPHA. (TNF.ALPHA.) Inhibits Progesterone and Estradiol-17.BETA. Production from Cultured Granulosa Cells: Presence of TNF.ALPHA. Receptors in Bovine Granulosa and Theca Cells

Sakumoto

Shibaya

Okuda

2003

Journal of Reproduction and Development

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Abstract. 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. Key words: Tumor necrosis factor-α, Receptor, Ovary, Bovine (J. Reprod. Dev. 49: [441][442][443][444][445][446][447][448][449] 2003) umor necrosis factor-α (TNFα) has been identified in the follicles of many species, including rats [1], mice [2], rabbits [3] and humans [4]. Furthermore, it has been shown that TNFα m o d ula tes bas a l o r g on ad o tr o pi n-in d uc ed s ter o ido genes is a nd pr o tein pro du ct ion in granulosa and theca cells in vitro [5]. Therefore, it is lik ely t hat lo cally pro d uced T NFα plays a physiological role in the regulation of ovarian function in several species.Immunoreactive or bioactive TNFα is present in bovine follicles during follicular development [6]. It has been demonstrated that TNFα inhibits follicle stimulating hormone (FSH)-, insulin-or insulin-like growth factor-I (IGF-I)-induced estradiol-17β (E2) production by granulosa cells of the small antral follicles [7,8]. In addit ion, T NF α inhibits l u t e i n i z i n g h o r m o n e ( L H ) -s t i m u l a t e d

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Section: Discussionsupporting

confidence: 64%

Section: Discussionmentioning

confidence: 87%

Tumor Necrosis Factor-.ALPHA. (TNF.ALPHA.) Inhibits Progesterone and Estradiol-17.BETA. Production from Cultured Granulosa Cells: Presence of TNF.ALPHA. Receptors in Bovine Granulosa and Theca Cells

Sakumoto

Shibaya

Okuda

2003

Journal of Reproduction and Development

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“…Immunoreactive TNF-a has been localized in the human granulosa cell layer of healthy antral follicles, in the ooplasm of the oocyte, and can be measured in human follicular¯uid (14,15). Granulosa cells collected from patients undergoing in vitro fertilization released TNF-a into the culture medium over a 15-h incubation period (15).…”

Section: Introductionmentioning

confidence: 99%

Plasma soluble tumor necrosis factor-alpha receptors circulate in proportion to leptin levels during the menstrual cycle in lean but not in obese women

Fernández-Real¹,

Gutiérrez

Vendrell

et al. 2000

European Journal of Endocrinology

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Objective: In recent studies serum leptin levels were signi®cantly higher in the luteal phase than in the follicular phase, but the mechanism of changing leptin levels are unknown. Several research lines indicate a potential role for tumor necrosis factor (TNF-a) in ovulation and reproductive events. As TNF-a appears to regulate leptin secretion, we speculated that TNF-a might be involved in leptin variations during the menstrual cycle. Design and methods: Nine healthy never obese and ten overweight normally cycling women were studied. TNF-a action ± through the plasma levels of the soluble fraction of the tumor necrosis factor receptors 1 and 2 (sTNFR1 and sTNFR2) ± and leptin concentrations were measured in the follicular (F), peri-ovulatory (PO) and luteal phases (L) of their menstrual cycles. Results: Circulating leptin levels were signi®cantly associated with the stage of the menstrual cycle (P<0.001), being higher in PO and L phases. However, only three of ten overweight subjects vs eight of nine lean women (Chi square P 0.014 after Fisher's exact test) showed signi®cantly higher leptin levels in the PO and L than in the F phase (95% con®dence interval (95% CI) of the differences, 3.7 to 10.2 ng/ml, paired t-test P 0.001). In these women (group 1), the changes in leptin levels parallelled the variations observed in plasma sTNFR1 (2.50 6 0.1 vs 2.11 6 0.05 ng/ml, P < 0.0001, 95% CI, 0.21 to 0.56) and sTNFR2 levels (5.19 6 0.28 vs 4.55 6 0.25 ng/ml, P < 0.0001, 95% CI, 0.47 to 0.81). In the remaining women (group 2), leptin (95% CI, ±1 to 9.2 ng/ml, P not signi®cant (NS)), sTNFR1 (95% CI, ±0.3 to 0.14 ng/ml, P NS) and sTNFR2 levels (95% CI, ±0.95 to 0.39 ng/ml, P NS) were essentially unaltered throughout the menstrual cycle. Group 2 women were similar in age (36.1 6 2.9 vs 37.3 6 1.4 years) and signi®cantly overweight (body mass index 31 6 2.9 vs 23.9 6 1.2 kg/m 2 ) compared with group 1 women. A negative correlation was observed between leptin levels in the follicular phase and the change in plasma leptin from F to L phase in all subjects (r À 0.67, P 0.002). Conclusions: Circulating leptin and sTNFRs levels change signi®cantly during the menstrual cycle of most lean women. In contrast, the levels of these molecules remain essentially unaltered during the F, PO and L phases in the majority of overweight women. Obesity might be associated not only with blunted diurnal excursions and dampened pulsatility, but also with blunted excursions during the menstrual cycle.

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“…While the majority of studies reported inhibitory effects (1-3) others reported stimulation (4,5) and some no effects at all (6,7). The use of different animals and different experimental models may have been partially responsible for such discrepancies.…”

Section: Introductionmentioning

confidence: 99%

Interactions between interleukin-1 beta, nitric oxide and prostaglandin E2 in the rat ovary: effects on steroidogenesis

Ahsan

Lacey

Whitehead

1997

European Journal of Endocrinology

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It has been reported that interleukin (IL)-1 b induces the synthesis of both nitric oxide (NO) and prostaglandin (PG)E 2 in cultures of dispersed ovarian cells and exerts cytotoxic effects on these cells. Since PGE 2 , NO and IL-1 b have been implicated as modulators of steroidogenesis, experiments have been undertaken to determine how IL-1 b -induced NO and PGE 2 production may affect steroidogenesis in cultures of ovarian dispersates obtained from untreated adult oestrous rats and to compare the action of IL-1 b in cultures of granulosa/luteal (GL) cell-only cultures and GL cells co-cultured with peritoneal macrophages.IL-1 b significantly increased the production of NO (assessed by nitrite measured in the culture medium) and PGE 2 in cultures of ovarian dispersates but had no effect on cultures of GL cells in which NO production was typically very low and PGE 2 production was undetectable. In contrast both NO and PGE 2 were high in co-cultures and were not significantly altered by the addition of IL-1 b . The NO donor sodium nitroprusside inhibited steroidogenesis in cultures of ovarian cells in a dose-dependent manner while PGE 2 had a stimulatory effect. Concomitant inhibition of NO production with aminoguanidine and PG production with indomethacin resulted in a significant enhancement of basal progesterone production in these cultures. Finally, IL-1 b inhibited progesterone responses to forskolin and PGE 2 in ovarian dispersates; an effect not observed in GL cell-only cultures nor in co-cultures in which forskolin-induced progesterone production is always inhibited. No cytotoxic effects of IL-1 b during the 48 h period of culture were observed. A comparison of the steroidogenic NO and PGE 2 responses to IL-1 b in the three culture models suggests that (i) the responses to IL-1 b observed in ovarian dispersates could be due to cytokine activation of resident and infiltrating macrophages or that the action of IL-1 b requires some other heterologous cell-cell contact, and (ii) IL-1 b acts indirectly on signal transduction pathways which stimulate steroidogenesis.

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Granulosa cells as a source and target organ for tumor necrosis factor‐α

Cited by 136 publications

References 10 publications

Tumor Necrosis Factor-.ALPHA. (TNF.ALPHA.) Inhibits Progesterone and Estradiol-17.BETA. Production from Cultured Granulosa Cells: Presence of TNF.ALPHA. Receptors in Bovine Granulosa and Theca Cells

Tumor Necrosis Factor-.ALPHA. (TNF.ALPHA.) Inhibits Progesterone and Estradiol-17.BETA. Production from Cultured Granulosa Cells: Presence of TNF.ALPHA. Receptors in Bovine Granulosa and Theca Cells

Plasma soluble tumor necrosis factor-alpha receptors circulate in proportion to leptin levels during the menstrual cycle in lean but not in obese women

Interactions between interleukin-1 beta, nitric oxide and prostaglandin E2 in the rat ovary: effects on steroidogenesis

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