Prostaglandins Mediate the Stimulation of Deoxyribonucleic Acid Synthesis by Transforming Growth Factor α in Hen Granulosa Cells during Ovarian Follicular Development1

Li, Julang; Tsang, Benjamin K.

doi:10.1095/biolreprod52.5.1050

Cited by 17 publications

(5 citation statements)

References 33 publications

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“…In the granulosa cells, inhibin-α expression is stimulated by LH, FSH, cAMP analogs, and activin [2,16,37,41,46,47], whereas treatment with GnRH, protein kinase C activator, estradiol and estradiol with progesterone suppress FSH-stimulated inhibin-α expression [2,15,37,41]. Transforming growth factor (TGF)-α/epidermal growth factor (EGF) is thought to be a primary mitogen of granulosa cells [21], and the arachidonic acid metabolites by PGS, not the lipoxygenase metabolites, mediate the mitogenic effects of TGF-α/EGF, as demonstrated in the hen granulosa cells [17]. These investigations, along with previous studies [12][13][14], suggest that indomethacin treatment of immature female rats disrupts mitosis of the granulosa cells in the growing follicles, the major source of inhibin and estradiol, thereby decreasing peripheral inhibin levels and suppressing estradiol increase.…”

Section: Discussionmentioning

confidence: 99%

Effects of Indomethacin on the Selective Release of Follicle-Stimulating Hormone during the Period of Ovulation in the Rat.

Shirota

Watanabe

Taya

et al. 1998

The Journal of Veterinary Medical Science

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ABSTRACT. To determine whether indomethacin, a potent inhibitor of prostaglandins endoperoxide synthetase, affects the selective folliclestimulating hormone (FSH) surge during the period of ovulation, the compound was administered intravenously (iv), concurrent with 10 IU human chorionic gonadotropin (hCG), to diestrous female rats at 16:00 hr. Indomethacin inhibited the number of ovulations in a dosedependent manner, and treatment with 500 µg indomethacin reduced number of oocytes in the ampullae most effectively without enteric lesions. In the histological observation, oocytes that had began to mature were found not only in unruptured luteinized follicles but also in ovarian interstitium beneath ruptured luteinized follicle. Despite the inhibitory effects of indomethacin on ovulation, peri-ovulatory FSH and progesterone surges occurred in comparable levels and duration to vehicle-treated animals. These results indicate that indomethacininduced inhibition of prostaglandin synthesis does not affect the selective release of FSH during the peri-ovulatory period. [30], and that pretreatment with indomethacin reduces these effects of PGs on hypothalamicpituitary axis [32]. On the other hand, indomethacin decreased peripheral levels of inhibin during the period of eguine chorionic gonadotropin (eCG)-stimulated and -non stimulated folliclular development in immature rats [12][13][14] with an increase of peripheral FSH level [13]. However, these reports do not provide an answer to the question whether indomethacin treatment at the dose level to inhibit ovulation affects the secondary FSH surge which has been observed during the period of ovulation.The present study was undertaken to predict whether indomethacin affects the secondary FSH surge, and effects of indomethacin on the selective release of FSH during the period of induction of ovulation in diestrous rats by hCG [28] were examined by measuring plasma levels of FSH after concurrent injection of hCG and indomethacin at the dose level to inhibit inducing ovulation. Plasma levels of LH and progesterone were also determined to examine effects of the compound on hypothalamic-pituitary axis and luteinization, respectively, and histological changes in the ovary were examined for oocyte maturation and ovulation. The present results provide the evidence that indomethacin at the dose level to inhibit ovulation does not affect the selective release of FSH during the period of ovulation, suggesting that PGS-generated arachidonic acid metabolites might not be involved in the rapid fluctuation of inhibin/ activin biosynthesis during this period. Ovulation is the process by which gametes are supplied for fertilization; in addition, ovulation promotes the ensuing ovulatory cycles unless fertilization has occurred in the rat. Once preovulatory gonadotropin surges occur, mitotic maturation of the oocytes is initiated and is followed by luteinization of the granulosa cells and rupture of folliclular walls in the Graaffian follicle. A new set of follicles, which reach the antral s...

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Section: Discussionmentioning

confidence: 99%

Effects of Indomethacin on the Selective Release of Follicle-Stimulating Hormone during the Period of Ovulation in the Rat.

Shirota

Watanabe

Taya

et al. 1998

The Journal of Veterinary Medical Science

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“…Specifically, tumor necrosis factor alpha (TNF␣) is an inhibitor of gonadotropin-induced differentiation [3][4][5][6][7] and transforming growth factor alpha (TGF␣) is an established mitogenic [8][9][10][11][12], antidifferentiative [13], and antiapoptotic [14] factor for granulosa cells during follicular development. In addition, recent studies on mammalian [15] and avian [16] granulosa cells have suggested that TNF␣ is proapoptotic prior to follicular selection at the antral and large white follicle stage of development in mammalian and avian species, respectively.…”

Section: Introductionmentioning

confidence: 99%

Follicular Stage-Dependent Tumor Necrosis Factor α-Induced Hen Granulosa Cell Integrin Production and Survival in the Presence of Transforming Growth Factor α In Vitro1

Soboloff

Sasaki

Tsang

2001

Biology of Reproduction

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The link between cell adhesion to extracellular matrix and integrin-mediated survival signals has been established in several physiological systems, and roles for the cytokines tumor necrosis factor alpha (TNF alpha) and transforming growth factor alpha (TGF alpha) have been suggested. TGF alpha stimulates fibronectin production in hen granulosa cells and is an important survival factor during follicular maturation. In contrast, the role of TNF alpha and its possible interaction with TGF alpha in the regulation of granulosa cell fate (death versus survival) during ovarian follicular development have not been fully elucidated. The object of the current study was to determine if TNF alpha and TGF alpha interact in the regulation of hen granulosa cell fibronectin and integrin content in the context of cell death and survival during follicular development. TGF alpha (0.1 or 10 ng/ml), but not TNF alpha (0.1 or 10 ng/ml), increased both cellular and secreted fibronectin content in granulosa cell cultures of F5,6 but not F1 follicles. The expression of integrin beta(3) subunit was also stimulated by TGF alpha in a follicular stage-dependent manner, and culture of F5,6 granulosa cells with TNF alpha in the presence of maximal stimulatory concentrations of TGF alpha potentiated this response. TGF alpha increased both F5,6 and F1 granulosa cell [(3)H]thymidine incorporation but not 3-(4,5-dimethylthiazol-2-yl)3,5-diphenyl tetrazolium bromide (MTT) metabolism. Although TNF alpha had no effect on [(3)H]thymidine incorporation irrespective of the presence of the growth factor, MTT metabolism was higher in F5,6 granulosa cells cultured for 24 h with both TNF alpha and TGF alpha than with either cytokine alone. Incubation of F5,6 granulosa cells for 48 and 72 h resulted in a TGF alpha-inhibited loss of cellular adhesion and detachment of granulosa cells from the growth surface. Although TNF alpha alone had no effect on cell morphology, it facilitated the reorganization of the granulosa cells into multicellular follicle-like structures in the presence of the growth factor. DNA degradation significantly increased between 0 and 72 h of culture in the absence of the cytokine but was suppressed by the addition of TGF alpha but not of TNF alpha. However, fluorometric analysis indicated that the primary type of cell death exhibited by F5,6 granulosa cells during extended culture and attenuated by the presence of TNF alpha and TGF alpha was necrosis and not apoptosis. The current study demonstrates that TNF alpha and TGF alpha interact in the regulation of granulosa cell integrin content and cell survival in vitro in a follicular stage-dependent manner. These findings suggest that follicular development is accompanied by a change in the intraovarian role of TNF alpha; it is atretogenic prior to follicular selection but prevents follicular demise during preovulatory growth.

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“…Previous studies from our laboratory have demonstrated that the synthesis and action of PGs are important events in the biochemical cascade for the induction of DNA synthesis in hen granulosa cells by TGFot. Like TGFa, PGs are more effective in stimulating DNA synthesis at an early stage than at a late stage of follicular development [18]. In addition, the role of PG in the regulation of granulosa cell differentiation has also been extensively reported, and PGs of the E series are known to stimulate steroidogenesis in granulosa cells [6].…”

Section: Discussionmentioning

confidence: 99%

“…Granulosa cell PG production and DNA synthesis were markedly stimulated by TGFo in vitro, the magnitude of these responses being dependent on the stage of follicular development. In addition, suppression of the growth factor-induced PG production by PLA 2 inhibitors was accompanied by a significant decrease in the proliferative response of the cells, which was effectively reversed by exogenous PGs of the E series [18], suggesting the possible involvement of PLA 2 in this process. Recent studies have demonstrated the regulation of cPLA 2 by interleukin-1 in cultured whole ovarian dispersates of immature rats [19,20].…”

Section: Introductionmentioning

confidence: 92%

“…Ovarian follicular development is the culmination of coordinated proliferative and differentiative activities of both granulosa and theca cells. Granulosa cell proliferation and differentiation are regulated by gonadotropins and various intraovarian factors [11][12][13][14][15][16][17], many of whose actions are dependent on the synthesis and action of PGs [2,18]. Previous studies from our laboratory have demonstrated that an increase in PG production in avian granulosa cells is a necessary element in the TGFa-regulated cascade of biochemical events leading to mitogenesis during ovarian follicular development.…”

Section: Introductionmentioning

confidence: 99%

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Regulation of Cytosolic Phospholipase A2 in Hen Granulosa Cells by Transforming Growth Factors at Different Stages of Follicular Development1

Tsang

1997

Biology of Reproduction

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Phospholipase A2 (PLA2) is a key enzyme involved in the release of arachidonic acid and subsequent production of prostaglandins (PGs), which play important roles in regulating ovarian function, including mitogenic signalling by transforming growth factor (TGF) alpha. Cytosolic PLA2 (cPLA2), a newly identified member of the PLA2 family, is distinct from the well-characterized, secreted 14-kDa group I and II PLA2 in that cPLA2 selectively cleaves arachidonic acid-containing phospholipids at the sn-2 position. Our previous studies have demonstrated that TGF alpha stimulates and TGF beta suppresses PG production in hen granulosa cells during ovarian follicular development. The present work extends these findings. A cPLA2 is present as a 100-kDa protein doublet and has a transcript size of 3.2 kilobases (kb) in hen granulosa cells from the largest (F1) and the fifth and sixth (F5-6) preovulatory follicles. Treatment of these cells with TGF alpha caused a shift from an electrophoretically fast-migrating to slow-migrating protein, a phenomenon sensitive to inhibitors of serine/threonine kinase as well as mitogen-activated protein (MAP) kinase pathways and indicative of phosphorylation and activation of cPLA2. In contrast, TGF beta suppressed cPLA2 expression, as evidenced by a marked decrease of cPLA2 mRNA abundance and protein content, but failed to prevent the mobility shift of cPLA2 induced by TGF alpha. Consistent with the influence of this growth factor on PG production observed previously and in contrast to the action of TGF alpha, the inhibition of cPLA2 by TGF beta is more pronounced in granulosa cells at the early stage of follicular development. Our results demonstrate, for the first time, the regulation of granulosa cell cPLA2 at the transcriptional and posttranscriptional levels at different stages of follicular development. We propose that the activation by TGF alpha and suppression by TGF beta of cPLA2 may be important regulatory mechanisms in the control of granulosa cell PG production and thereby the mitogenic response of the cells to the growth factors during ovarian follicular development.

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Prostaglandins Mediate the Stimulation of Deoxyribonucleic Acid Synthesis by Transforming Growth Factor α in Hen Granulosa Cells during Ovarian Follicular Development1

Cited by 17 publications

References 33 publications

Effects of Indomethacin on the Selective Release of Follicle-Stimulating Hormone during the Period of Ovulation in the Rat.

Effects of Indomethacin on the Selective Release of Follicle-Stimulating Hormone during the Period of Ovulation in the Rat.

Follicular Stage-Dependent Tumor Necrosis Factor α-Induced Hen Granulosa Cell Integrin Production and Survival in the Presence of Transforming Growth Factor α In Vitro1

Regulation of Cytosolic Phospholipase A2 in Hen Granulosa Cells by Transforming Growth Factors at Different Stages of Follicular Development1

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