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Keiko Yasuda - One of the best experts on this subject based on the ideXlab platform.
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the roles of thy1 and integrin beta3 in Cell adhesion during Theca Cell layer formation and the effect of follicle stimulating hormone on thy1 and integrin beta3 localization in mouse ovarian follicles
Biology of Reproduction, 2011Co-Authors: Saori Itami, Atsushi Sakai, Satoshi Tamotsu, Keiko YasudaAbstract:The mechanism of Theca Cell layer formation in mammalian ovaries has not been elucidated. In the present study, we examined the roles of THY1 and integrin beta3 in Theca Cell layer formation during mouse folliculogenesis. The localization pattern of THY1 and integrin beta3 in adult mouse ovary was investigated immunohistochemically. The strongest THY1 signal was observed in Theca Cell layers from secondary to preantral follicles, at which time Theca Cells have begun to participate in follicle formation. Integrin beta3 also localized to the Theca Cell layer of secondary to preantral follicles and showed a localization pattern similar to that of THY1. Moreover, the role of THY1 in Theca Cell layer formation was examined using a follicle culture system. When anti-THY1 antibody was added to this culture, no Theca Cell layers were formed, and the granulosa Cells were distanced from each other. Because a THY1 signal was not observed in ovaries at stages earlier than prepuberty, THY1 localization also appeared to be affected by mouse development. This possibility was examined by determining the effect of administering follicle-stimulating hormone, luteinizing hormone, and 17beta-estradiol to 7-day-old mice on THY1 localization in the ovary 3 days later. Only follicle-stimulating hormone induced a THY1 signal in 10-day-old mouse ovaries. No THY1 signal was observed in untreated 10-day-old ovaries. In conclusion, THY1 might play a role in Cell adhesion via binding to integrin beta3 in mouse ovaries. The present results suggest that THY1 localization may be affected by follicle-stimulating hormone in mouse ovaries.
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Co-culturing of follicles with interstitial Cells in collagen gel reproduce follicular development accompanied with Theca Cell layer formation.
Reproductive Biology and Endocrinology, 2011Co-Authors: Saori Itami, Keiko Yasuda, Yuka Yoshida, Chiyuki Matsui, Sachie Hashiura, Atsushi Sakai, Satoshi TamotsuAbstract:Background The mechanism of Theca Cell layer formation in mammalian ovaries has not been elucidated; one reason is that there is no follicle culture system that can reproduce Theca Cell layer formation in vitro. Therefore, a three-dimensional follicle culture system that can reproduce Theca Cell layer formation is required.
Aaron J W Hsueh - One of the best experts on this subject based on the ideXlab platform.
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growth differentiation factor 9 gdf9 stimulates proliferation and inhibits steroidogenesis by bovine Theca Cells influence of follicle size on responses to gdf9
Biology of Reproduction, 2008Co-Authors: L J Spicer, D T Allen, Sabine Mazerbourg, Anita H Payne, Aaron J W HsuehAbstract:Ovarian follicular development is controlled by numerous paracrine and endocrine regulators, including oocyte-derived growth differentiation factor 9 (GDF9), and a localized increase in bioavailable insulin-like growth factor 1 (IGF1). The effects of GDF9 on function of Theca Cells collected from small (3–6 mm) and large (8–22 mm) ovarian follicles were investigated. In smallfollicle Theca Cells cultured in the presence of both LH and IGF1, GDF9 increased Cell numbers and DNA synthesis, as measured by a 3 H-thymidine incorporation assay, and dose-dependently decreased both progesterone and androstenedione production. Theca Cells from large follicles had little or no response to GDF9 in terms of Cell proliferation or steroid production induced by IGF1. Small-follicle Theca Cell studies indicated that GDF9 decreased the abundance of LHR and CYP11A1 mRNA in Theca Cells, but had no effect on IGF1R, STAR ,o rCYP17A1 mRNA abundance or the percentage of Cells staining for CYP17A1 proteins. GDF9 activated similar to mothers against decapentaplegics (SMAD) 2/3-induced CAGA promoter activity in transfected Theca Cells. Small-follicle Theca Cells had more ALK5 mRNA than large-follicle Theca Cells. Small-follicle granulosa Cells appeared to have greater GDF9 mRNA abundance than large-follicle granulosa Cells, but Theca Cells had no detectable GDF9 mRNA. We conclude that Theca Cells from small follicles are more responsive to GDF9 than those from large follicles and that GDF9 mRNA may be produced by granulosa Cells in cattle. Because GDF9 increased Theca Cell proliferation and decreased Theca Cell steroidogenesis, oocyteand granulosa Cell-derived GDF9 may simultaneously promote Theca Cell proliferation and prevent premature differentiation of the Theca interna during early follicle development.
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in vivo treatment with gdf 9 stimulates primordial and primary follicle progression and Theca Cell marker cyp17 in ovaries of immature rats
Endocrinology, 2000Co-Authors: Ursula A Vitt, Elizabeth A Mcgee, Masaru Hayashi, Aaron J W HsuehAbstract:Growth differentiation factor (GDF)-9 is a cystine knot-containing hormone of the transforming growth factor-β superfamily produced by the oocyte. In GDF-9 null mice, follicle development is arrested at the primary stage and GDF-9 treatment in vitro enhances preantral follicle growth. Immature female rats were treated with recombinant GDF-9 for 7 or 10 days. At 10 days, treatment with GDF-9 augmented ovarian weights, concomitant with an increase in the number of primary and small preantral follicles by 30 and 60%, respectively. Furthermore, the number of primordial follicles was decreased by 29%, but the number of large preantral follicles was not affected. In contrast, treatment with FSH increased the number of small and large preantral follicles by 36 and 177% but did not influence the number of primary and primordial follicles. Immunoblot analysis showed an increase of CYP17, a Theca Cell marker, in the ovarian homogenate after treatment with GDF-9 but not FSH. The present results indicate that in vivo...
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growth differentiation factor 9 stimulates rat Theca interstitial Cell androgen biosynthesis
Biology of Reproduction, 2000Co-Authors: Elena V Solovyeva, Aaron J W Hsueh, Masaru Hayashi, Karen Margi, Claudine Barkats, Cynthia Klein, Abraham Amsterdam, A TsafririAbstract:Growth differentiation factor-9 (GDF-9) was shown recently to be essential for early follicular development, including the appearance of the Theca layer. Theca Cells provide the androgen substrate for aromatization and estrogen production by granulosa Cells. Using biologically active recombinant GDF-9 (rGDF-9) and an androgen-producing immortalized Theca-interstitial Cell (TIC) line or primary TIC, we have examined the action of this paracrine hormone on Theca Cell steroidogenesis. The effect of GDF-9 on TIC progesterone synthesis was marginal and inconsistent in the primary cultures. In immortalized Theca Cells, GDF-9 attenuated the forskolin-stimulated progesterone accumulation. More significantly, this oocyte-derived growth factor enhanced both basal and stimulated androstenedione accumulation in the primary and transformed TIC cultures. The effects of GDF-9 on steroidogenesis by preovulatory follicles were relatively modest. Likewise, it did not affect the maturation of follicle-enclosed oocytes. The effect of GDF-9, an oocyte product, on TIC androgen production suggests a regulatory role of the oocyte on Theca Cell function and hence on follicle development and differentiation. This direct effect of GDF-9 on Thecal steroidogenesis is consistent with its recently demonstrated actions on Thecal Cell recruitment and differentiation.
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equine granulosa Theca Cell tumors express inhibin alpha and beta a subunit messenger ribonucleic acids and proteins
Biology of Reproduction, 1990Co-Authors: Gary N Piquette, R M Kenney, P L Sertich, Mareo Yamoto, Aaron J W HsuehAbstract:The association of equine granulosa-Theca Cell tumors with atrophied contralateral ovaries and abnormal estrous cycles suggests that these tumors produce hormones that affect pituitary gonadotropin production. Because inhibin, a heterodimer protein secreted by granulosa Cells, decreases FSH production, we examined the presence of inhibin alpha- and beta A-subunits and their mRNAs in ovarian tumors obtained from three mares. These tumors contained neoplastic cords and nodules, multiple fluid-filled cysts, and a predominance of neoplastic granulosa Cells. Reduced proteins from tumor-conditioned media were analyzed by electrophoresis and immunoblotting using antibodies directed against peptide fragments of the alpha- and beta A-chains of porcine inhibin. Specific bands at 50-kDa and 36-kDa for the inhibin alpha-subunit and at 44 kDa and 13 kDa for the inhibin beta A-subunit were observed in these tumors. Northern blot hybridization of 32P-labeled rat inhibin alpha- and beta A-subunit complementary RNAs to total RNA from each tumor revealed predominant bands of activity in all three tumors at 1.5 and 7 kb for the alpha- and beta A-subunit mRNAs, respectively. These results demonstrate that equine granulosa-Theca Cell tumors express the mRNAs for inhibin alpha- and beta A-subunits and also secrete inhibin subunits that could potentially affect gonadotropin production in afflicted mares. Furthermore, Cells derived from these tumors may provide a useful model for understanding inhibin gene regulation and ovarian tumorigenesis.
Saori Itami - One of the best experts on this subject based on the ideXlab platform.
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the roles of thy1 and integrin beta3 in Cell adhesion during Theca Cell layer formation and the effect of follicle stimulating hormone on thy1 and integrin beta3 localization in mouse ovarian follicles
Biology of Reproduction, 2011Co-Authors: Saori Itami, Atsushi Sakai, Satoshi Tamotsu, Keiko YasudaAbstract:The mechanism of Theca Cell layer formation in mammalian ovaries has not been elucidated. In the present study, we examined the roles of THY1 and integrin beta3 in Theca Cell layer formation during mouse folliculogenesis. The localization pattern of THY1 and integrin beta3 in adult mouse ovary was investigated immunohistochemically. The strongest THY1 signal was observed in Theca Cell layers from secondary to preantral follicles, at which time Theca Cells have begun to participate in follicle formation. Integrin beta3 also localized to the Theca Cell layer of secondary to preantral follicles and showed a localization pattern similar to that of THY1. Moreover, the role of THY1 in Theca Cell layer formation was examined using a follicle culture system. When anti-THY1 antibody was added to this culture, no Theca Cell layers were formed, and the granulosa Cells were distanced from each other. Because a THY1 signal was not observed in ovaries at stages earlier than prepuberty, THY1 localization also appeared to be affected by mouse development. This possibility was examined by determining the effect of administering follicle-stimulating hormone, luteinizing hormone, and 17beta-estradiol to 7-day-old mice on THY1 localization in the ovary 3 days later. Only follicle-stimulating hormone induced a THY1 signal in 10-day-old mouse ovaries. No THY1 signal was observed in untreated 10-day-old ovaries. In conclusion, THY1 might play a role in Cell adhesion via binding to integrin beta3 in mouse ovaries. The present results suggest that THY1 localization may be affected by follicle-stimulating hormone in mouse ovaries.
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Co-culturing of follicles with interstitial Cells in collagen gel reproduce follicular development accompanied with Theca Cell layer formation.
Reproductive Biology and Endocrinology, 2011Co-Authors: Saori Itami, Keiko Yasuda, Yuka Yoshida, Chiyuki Matsui, Sachie Hashiura, Atsushi Sakai, Satoshi TamotsuAbstract:Background The mechanism of Theca Cell layer formation in mammalian ovaries has not been elucidated; one reason is that there is no follicle culture system that can reproduce Theca Cell layer formation in vitro. Therefore, a three-dimensional follicle culture system that can reproduce Theca Cell layer formation is required.
Michael I Maggio - One of the best experts on this subject based on the ideXlab platform.
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synchronous bilateral testis tumor mixed germ Cell and Theca Cell tumors
Urology, 1993Co-Authors: Noah S Schenkman, Judd W Moul, Eric R Nicely, Michael I MaggioAbstract:Abstract Synchronous bilateral testis tumors of different histologic types are rare. All previous cases have demonstrated germ Cell tumors on both sides. The simultaneous appearance of a germ Cell tumor and a contralateral non-germ Cell tumor has not been reported. We herein report a thirty-four-year-old man who presented with a mixed nonseminomatous germ Cell tumor of the left testis and Theca Cell tumor of the right testis.
Michael K Skinner - One of the best experts on this subject based on the ideXlab platform.
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Regulation of granulosa and Theca Cell transcriptomes during ovarian antral follicle development.
Molecular Reproduction and Development, 2008Co-Authors: Michael K Skinner, Michelle A. Schmidt, Marina I. Savenkova, Ingrid Sadler-riggleman, Eric E NilssonAbstract:Coordinated interactions between ovarian granulosa and Theca Cells are required for female endocrine function and fertility. To elucidate these interactions the regulation of the granulosa and Theca Cell transcriptomes during bovine antral follicle development were investigated. Granulosa Cells and Theca Cells were isolated from small ( 10 mm) antral bovine follicles. A microarray analysis of 24,000 bovine genes revealed that granulosa Cells and Theca Cells each had gene sets specific to small, medium and large follicle Cells. Transcripts regulated (i.e., minimally changed 1.5-fold) during antral follicle development for the granulosa Cells involved 446 genes and for Theca Cells 248 genes. Only 28 regulated genes were common to both granulosa and Theca Cells. Regulated genes were functionally categorized with a focus on growth factors and cytokines expressed and regulated by the two Cell types. Candidate regulatory growth factor proteins mediating both paracrine and autocrine Cell-Cell interactions include macrophage inflammatory protein (MIP1 beta), teratocarcinoma-derived growth factor 1 (TDGF1), stromal derived growth factor 1 (SDF1; i.e., CXCL12), growth differentiation factor 8 (GDF8), glia maturation factor gamma (GMFG), osteopontin (SPP1), angiopoietin 4 (ANGPT4), and chemokine ligands (CCL 2, 3, 5, and 8). The current study examined granulosa Cell and Theca Cell regulated genes associated with bovine antral follicle development and identified candidate growth factors potentially involved in the regulation of Cell-Cell interactions required for ovarian function.
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growth and differentiation factor 9 stimulates progression of early primary but not primordial rat ovarian follicle development
Biology of Reproduction, 2002Co-Authors: Eric E Nilsson, Michael K SkinnerAbstract:The ovary contains a pool of primordial follicles containing oocytes arrested in meiosis that are the source of developing follicles for the female. Growth and differentiation factor-9 (GDF-9) is a member of the transforming growth factor beta superfamily of growth factors, and follicles of GDF-9 knockout mice arrest in the primary stage of development. The effect of GDF-9 treatment on the primordial to primary follicle transition and on subsequent follicle progression was examined using a rat ovary organ culture system. Ovaries from 4-day-old rats were cultured under serum-free conditions in the absence or presence of growth factors. GDF-9 treatment caused a decrease in the proportion of stage 1 early primary follicles and a concomitant increase in the proportion of stage 2 mature primary follicles. GDF-9 did not effect primordial follicles or stage 0 to stage 1 follicle transition. GDF-9 also did not influence stage 3 or 4 secondary follicle numbers. Isolated antral follicle granulosa and Theca Cell cultures were used to analyze the actions of GDF-9. GDF-9 treatment did not directly influence either granulosa or Theca Cell proliferation. The ability of GDF-9 to influence the expression of another growth factor was examined. GDF-9 treatment increased kit ligand (KL) mRNA expression in bovine granulosa Cells after 2 days of culture. Ovaries from 4-day-old rats were also cultured with or without GDF-9 treatment, and total ovary expression of KL mRNA was increased by GDF-9. In summary, GDF-9 was found to promote the progression of early primary follicle development but did not influence primordial follicle development. The actions of GDF-9 on specific stages of follicle development may in part be mediated through altering the expression of KL.
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Cellular interactions that control primordial follicle development and folliculogenesis
Journal of The Society for Gynecologic Investigation, 2001Co-Authors: Eric E Nilsson, Michael K SkinnerAbstract:: Specific factors that mediate local Cell--Cell interactions in the ovary related to the initiation and progression of follicle development will be discussed. Recently, several factors produced locally by the primordial follicle have been shown to induce primordial follicle development from a quiescent state to promote follicle development. Kit ligand/stem Cell factor (KL/SCF) produced by the immature granulosa Cells appears to promote Theca Cell organization. Basic fibroblast growth factor produced predominately by the oocyte, but by all Cells at reduced levels, also was found to induce primordial follicle development similar to KL. It is likely that numerous locally produced factors will mediate Cellular interactions and interact between each other to control the induction of primordial follicle development and influence processes such as the onset of puberty and menopause. After follicle development has been induced, Theca Cells and granulosa Cells interact through classical mesenchymal-epithelial type interactions to influence the progression of follicle development. Mesenchymally derived Theca Cells have been shown to produce transforming growth factor alpha (TGF-alpha), keratinocyte growth factor (KGF), hepatocyte growth factor (HGF), and transforming growth factor beta to regulate granulosa Cell growth and function. The epithelial granulosa Cells have been show to produce KL/SCF that can feed back on the Theca Cells to regulate Theca Cell growth and stimulate the production of the Theca Cell factors (TGF-alpha, KGF, and HGF). Therefore, a positive feedback loop between the Theca Cells and granulosa Cells appears to exist to promote the dramatic Cell growth required during folliculogenesis. Interestingly, hormones such as estrogen and gonadotropins stimulate the expression of these paracrine growth factors. Therefore, the actions of hormones to stimulate follicle development and growth are mediated in part through altering these local Cell--Cell interactions. In summary, the locally produced paracrine factors that mediate Cell-Cell interactions involved in primordial follicle development and the progression of follicle development during folliculogenesis are starting to be elucidated.
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Kit ligand actions on ovarian stromal Cells: effects on Theca Cell recruitment and steroid production.
Molecular Reproduction and Development, 2000Co-Authors: Jeff A. Parrott, Michael K SkinnerAbstract:Factors that control recruitment of Theca Cells from ovarian stromal-interstitial Cells are important for early follicle development in the ovary. During recruitment, Theca Cells organize into distinct layers around early developing follicles and establish essential Cell-Cell interactions with granulosa Cells. Recruitment of Theca Cells from ovarian stromal stem Cells is proposed to involve Cellular proliferation, as well as induction of Theca Cell-specific functional markers. Previously, the speculation was made that a granulosa Cell-derived "Theca Cell organizer" is involved in Theca Cell recruitment. Granulosa Cells have been shown to produce kit-ligand/stem Cell factor (KL). KL is known to promote stem Cell proliferation and differentiation in a number of tissues. Therefore, the hypothesis was tested in the current study that granulosa Cell-derived KL may help recruit Theca Cells from undifferentiated stromal stem Cells during early follicle development. The actions of KL were examined using adult bovine ovarian fragment organ culture and isolated ovarian stromal-interstitial Cells. In organ culture KL significantly increased the number of Theca Cell layers around primary follicles. Experiments using purified stromal-interstitial Cell cultures showed that KL stimulated ovarian stromal Cell proliferation in a dose-dependent manner. Stromal Cell differentiation into Theca Cells was analyzed by the induction of Theca Cell functional markers (i.e., androstenedione and progesterone production). Bovine ovarian stromal Cells produced low levels of androstenedione (5-40 ng/microg DNA) and progesterone (5-30 ng/microg DNA) in vitro that were approximately 20-fold lower than Theca Cells under similar conditions. Treatment with KL did not affect ovarian stromal Cell androstenedione or progesterone production. Interestingly, hormones such as estrogen and hCG did stimulate stromal Cell steroid production. The results in this study suggest that granulosa Cell-derived KL appears to promote the formation of Theca Cell layers around small (i.e., primary) ovarian follicles. KL directly stimulated ovarian stromal Cell proliferation but alone did not induce functional differentiation (i.e., high steroid production). Therefore, KL is proposed to promote early follicle development by inducing proliferation and organization of stromal stem Cells around small follicles. Observations suggest that KL may act as a granulosa-derived "Theca Cell organizer" to promote stem Cell recruitment of ovarian stromal Cells in a manner similar to the way that KL promotes hematopoietic and lymphoid stem Cells in bone marrow and the thymus.
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Direct actions of kit-ligand on Theca Cell growth and differentiation during follicle development.
Endocrinology, 1997Co-Authors: Jeff A. Parrott, Michael K SkinnerAbstract:The direct actions of kit-ligand/stem Cell factor (KL) in developing ovarian follicles were investigated. Previous studies have shown that granulosa Cells express KL that can support oocyte development. The current study demonstrates that KL can also act directly on Theca Cells to promote Cellular growth and differentiation. Through RT-PCR analysis it was shown that bovine granulosa Cells express KL, and Theca Cells express the receptor c-kit. Bovine Theca interna Cells were isolated and cultured in serum-free conditions to study KL actions. KL stimulated Theca Cell growth in a dose-dependent manner as measured by[ 3H]thymidine incorporation into DNA when Cells were cultured under subconfluent conditions. KL had no effect on Theca Cell androstenedione or progesterone production under these growth-permissive conditions. In contrast, KL stimulated Theca Cell androstenedione production but had no effect on progesterone production when Theca Cells were cultured under confluent (non-growth-permissive) conditio...