Modulatory Role of Epidermal Growth Factor in  Follicle-Stimulating Hormone-lnduced DNA Synthesis in Cultured Rat Granulosa Cells.

Liang, Shanshan; Yano, Tetsu; Tsutsumi, Osamu; Taketani, Yuji

doi:10.1507/endocrj.41.319

Cited by 4 publications

(5 citation statements)

References 24 publications

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“…In addition, both EGF, a mitogen and prodevelopmental substance for granulosa cells [1,20,21], and buserelin decreased iNOS mRNA levels in cultured rat granulosa cells. Along with our recent findings that iNOS mRNA and its protein are predominantly localized in the granulosa cells in immature follicles, but not in mature follicles with an antrum or atretic follicles [15,16], the present data further strengthen our hypothesis that NO produced by iNOS in immature follicles acts as a cytostatic factor [16].…”

Section: Discussionmentioning

confidence: 89%

“…More specifically, we employed two agents. The first, epidermal growth factor (EGF), is a mitogenic and antiapoptotic factor for granulosa cells and is supposed to be involved in follicular development, presumably, in part, by suppressing granulosa cell apoptosis [1,20,21]. The second, buserelin, is a GnRH agonist and is known to induce apoptosis and inhibit cell proliferation in granulosa cells [1,21].…”

Section: Introductionmentioning

confidence: 99%

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Regulation of Nitric Oxide Synthase to Promote Cytostasis in Ovarian Follicular Development1

Matsumi

Yano

Osuga

et al. 2000

Biology of Reproduction

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Our own recent studies have demonstrated that inducible nitric oxide synthase (iNOS) is predominantly localized in granulosa cells of healthy immature follicles in the rat ovary, whereas granulosa cells of either healthy mature follicles or follicles destined to be atretic are devoid of iNOS. These findings suggest that iNOS is pivotal for immature follicles to remain dormant. To test this hypothesis, we examined the effects of a GnRH agonist (buserelin), a proapoptotic substance, and epidermal growth factor (EGF), a mitogenic and, consequently, antiapoptotic factor, on the amount of iNOS mRNA in rat granulosa cells. Administration of buserelin in immature female rats transiently diminished iNOS mRNA levels in the ovaries as determined by Northern blot analysis. In cultured rat granulosa cells, buserelin and EGF increased the incidence of apoptosis and DNA synthesis, respectively, whereas both reduced iNOS mRNA levels as determined by reverse transcription-coupled polymerase chain reaction. The concomitant addition of S-nitroso-N-acetyl-DL-penicillamine, an NO donor, together with buserelin or EGF eliminated the observed effects of these substances (i.e., induction of apoptosis and stimulation of DNA synthesis, respectively). These results suggest that the changes in developmental status of immature follicles either into development or atresia are associated with reduced iNOS levels in granulosa cells, thus reinforcing the notion of NO as a cytostatic factor in ovarian follicles.

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Section: Discussionmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Regulation of Nitric Oxide Synthase to Promote Cytostasis in Ovarian Follicular Development1

Matsumi

Yano

Osuga

et al. 2000

Biology of Reproduction

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“…A scale bar of 500 µm is included. (Hsueh et al 1981, Downs 1989, Roy & Greenwald 1991, Das et al 1992, Liang et al 1994, Prochazka et al 2000. However, most of these data were obtained from in vitro studies, and the physiological functions of these growth factors continue to remain unclear.…”

Section: Discussionmentioning

confidence: 99%

“…The epidermal growth factor (EGF) family growth factors, EGF and transforming growth factor-(TGF-), are also thought to be involved in this process. Both act as mitogens (Roy & Greenwald 1991, Liang et al 1994) and modulators of FSH-stimulated steroid secretion (Hsueh et al 1981) in ovarian granulosa cells. Furthermore, EGF induces cumulus expansion and oocyte maturation that usually occurs after the preovulatory LH surge (Downs 1989, Das et al 1992, Prochazka et al 2000.…”

Section: Introductionmentioning

confidence: 99%

Expression of epiregulin and amphiregulin in the rat ovary

Sekiguchi¹,

Mizutani²,

Yamada³

et al. 2004

Journal of Molecular Endocrinology

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We have previously reported that the epidermal growth factor (EGF) family growth factor, epiregulin, is expressed in rat ovarian granulosa cells by induction with pregnant mare serum gonadotropin (PMSG). In this study, we report that amphiregulin, another member of the EGF family, was also induced in the rat ovary by gonadotropin treatment. Northern blot analysis revealed that PMSG treatment induced the expression of both epiregulin and amphiregulin mRNA after 24 h, but the expression then decreased 48 h after treatment. Further treatment with human chorionic gonadotropin (hCG) rapidly induced the expression of both epiregulin and amphiregulin genes and maximal levels were reached 4 h after hCG treatment. A marginal increase in amphiregulin mRNA levels was also observed 6 h after PMSG treatment. In situ hybridization revealed that epiregulin and amphiregulin mRNAs were localized in the granulosa cells of large antral follicles. These spatio-temporal expression patterns were similar to those of cyclo-oxygenase-2 (COX-2) and progesterone receptor (PR). In adult cycling rats, epiregulin and amphiregulin were strongly induced at 1800 and 2000 h on proestrus coinciding with the preovulatory LH surge. An in situ hybridization study also showed that epiregulin and amphiregulin mRNAs were detectable in the granulosa cells of preovulatory ovarian follicles at 2000 h on proestrus, where transcripts of COX-2 and PR were co-localized with those of epiregulin and amphiregulin. These observations suggested that the EGF family members, epiregulin and amphiregulin, may play a role in the ovulatory process of cycling rats as well as in the induction of ovulation in immature rats.

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“…The effect of EGF at the ovarian level was mainly studied in vitro. EGF stimulates the proliferation of rat and porcine granulosa cells [11,12]. This effect is likely regulated by LH and FSH [13].…”

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confidence: 95%

In Vivo Effect of Epidermal Growth Factor, Interleukin-1β, and Interleukin-1RA on Equine Preovulatory Follicles1

Martoriati

Duchamp

Gérard

2003

Biology of Reproduction

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Paracrine factors have significant effects during folliculogenesis. Because of various morphological features, the mare is a convenient model to study in vivo the effects of factors involved in periovulatory events. In the present work, epidermal growth factor (EGF; experiment 1, n = 49 mares) and interleukin-1beta and interleukin-1RA (IL-1beta and IL-1RA, respectively; experiment 2, n = 80 mares) were injected intrafollicularly to evaluate the influence of these factors on in vivo maturation of equine preovulatory follicles. A transvaginal ultrasound-guided injection was performed when the diameter of the dominant follicle reached 30-34 mm. In experiment 1, the four experimental groups were 1) EGF group, intrafollicular (i.f.) injection of EGF (2 ml; 0.5 microg/ml) plus i.v. injection of physiological serum; 2) control group, no injection; 3) PBS group, i.f. injection of 2 ml of PBS plus i.v. injection of physiological serum; 4) crude equine gonadotropins (CEG) group, i.f. injection of PBS plus i.v. injection of CEG (20 mg). In experiment 2, groups 3 and 4 were the same as in experiment 1, but groups 1 and 2 were changed as follows: 1) IL-1beta group, i.f. injection of IL-1beta (2 ml; 0.5 microg/ml) plus i.v. injection of physiological serum; 2) IL-1RA group, i.f. injection of IL-1RA (2 ml; 0.5 microg/ml) plus i.v. injection of physiological serum. In each experiment, cumulus-oocyte complexes from dominant/injected follicles were collected by transvaginal ultrasound-guided aspiration 38 h after intrafollicular injection. Cumulus morphology and oocyte nuclear stage were assessed. Additionally, in experiment 2, 40 mares were used to determine the time of ovulation after treatments. Our results indicate that intrafollicular injection of EGF or PBS induced lower cumulus expansion and oocyte maturation rates compared with the CEG group (P < 0.05). In experiment 2, the IL-1beta and CEG groups showed the same expansion rate, the same oocyte maturation rate, and the same ovulation distribution. On the other hand, the intrafollicular injection of IL-1RA, as PBS, did not induce follicle and cumulus-oocyte complex (COC) maturation. In conclusion, we confirmed that the technique of intrafollicular injection can be used in the mare to study the role of specific molecules. We demonstrated for the first time in mares that the injection of EGF did not influence in vivo COC maturation. In contrast, IL-1beta injection into the dominant follicle induced in vivo oocyte maturation and the ovulation process whereas IL-1RA seemed to block these mechanisms.

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Modulatory Role of Epidermal Growth Factor in Follicle-Stimulating Hormone-lnduced DNA Synthesis in Cultured Rat Granulosa Cells.

Cited by 4 publications

References 24 publications

Regulation of Nitric Oxide Synthase to Promote Cytostasis in Ovarian Follicular Development1

Regulation of Nitric Oxide Synthase to Promote Cytostasis in Ovarian Follicular Development1

Expression of epiregulin and amphiregulin in the rat ovary

In Vivo Effect of Epidermal Growth Factor, Interleukin-1β, and Interleukin-1RA on Equine Preovulatory Follicles1

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