Abstract:
:Estrogens are essential for female reproduction and overall well-being, and estrogens in the circulation are largely synthesized in ovarian granulosa cells. Using primary cultures of ovarian granulosa cells from gonadotropin-primed immature rats, we have recently discovered that pituitary FSH and ovarian cytokine transforming growth factor beta 1 (TGFβ1) induce calcineurin-mediated dephosphorylation-activation of cAMP-response element-binding protein (CREB)-regulated transcription coactivator (CRTC2) to modulate the expression of Star, Cyp11a1, and Hsd3b leading to increased production of progesterone. This study explored the role of calcineurin and CRTC2 in FSH and TGFβ1 regulation of Cyp19a1 expression in granulosa cells. Ovarian granulosa cells treated with FSH displayed increased aromatase protein at 24 h post-treatment, which subsided by 48 h, while TGFβ1 acting through its type 1 receptor augmented the action of FSH with a greater and longer effects. It is known that the ovary-specific Cyp19a1 PII-promoter contains crucial response elements for CREB and nuclear receptor NR5A subfamily liver receptor homolog 1 (LRH1/NR5A2) and steroidogenic factor 1 (SF1/NR5A1), and that the Nr5a2 promoter also has a potential CREB-binding site. Herein, we demonstrate that FSH+TGFβ1 increased LRH1 and SF1 protein levels, and their binding to the Cyp19a1 PII-promoter evidenced, determined by chromatin immunoprecipitation analysis. Moreover, pretreatment with calcineurin auto-inhibitory peptide (CNI) abolished the FSH+TGFβ1-upregulated but not FSH-upregulated aromatase activity at 48 h, and the corresponding mRNA changes in Cyp19a1, and Nr5a2 and Nr5a1 at 24 h. In addition, FSH and TGFβ1 increased CRTC2 binding to the Cyp19a1 PII-promoter and Nr5a2 promoter at 24 h, with CREB bound constitutively. In summary, the results of this study indicate that calcineurin and CRTC2 have important roles in mediating FSH and TGFβ1 collateral upregulation of Cyp19a1 expression together with its transcription regulators Nr5a2 and Nr5a1 in ovarian granulosa cells.
journal_name
J Mol Endocrinoljournal_title
Journal of molecular endocrinologyauthors
Lai WA,Yeh YT,Fang WL,Wu LS,Harada N,Wang PH,Ke FC,Lee WL,Hwang JJdoi
10.1530/JME-14-0048subject
Has Abstractpub_date
2014-10-01 00:00:00pages
259-70issue
2eissn
0952-5041issn
1479-6813pii
JME-14-0048journal_volume
53pub_type
杂志文章abstract::We have studied the action of peripheral blood lymphocytes (PBLs) and intrathyroidal lymphocytes (ITLs) on the biochemical and hormonal metabolism of autologous thyrocytes cultured in follicles in a collagen gel. The production of tumour necrosis factor alpha (TNF-alpha) in culture was also measured. Thyroid tissues a...
journal_title:Journal of molecular endocrinology
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journal_title:Journal of molecular endocrinology
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journal_title:Journal of molecular endocrinology
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journal_title:Journal of molecular endocrinology
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doi:10.1677/jme.0.0280137
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abstract::Murine double minute clone 2 (MDM2) is a multifunctional protein, which modulates nuclear receptor-mediated transactivation. In this study, we show that MDM2 significantly enhanced estrogen receptor α (ERα) and ERα/specificity protein-mediated transactivation in MCF-7 and ZR-75 breast cancer cells. This was demonstrat...
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journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
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journal_title:Journal of molecular endocrinology
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doi:10.1677/jme.0.0110037
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journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0130321
更新日期:1994-12-01 00:00:00
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更新日期:2005-12-01 00:00:00
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journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1530/JME-16-0116
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pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:2005-04-01 00:00:00
abstract::It has recently been shown that 20 kDa human growth hormone (hGH) forms the 1:2 hGH:hGH receptor (hGHR) complex and expresses full agonistic activity, although it hardly forms the 1:1 GH:GHR complex as compared with 22 kDa hGH. To clarify this mechanism, we analyzed the mode of receptor dimerization of 20 kDa hGH usin...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0230347
更新日期:1999-12-01 00:00:00
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journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1677/jme.0.0320571
更新日期:2004-04-01 00:00:00
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journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
doi:10.1530/JME-12-0202
更新日期:2013-01-11 00:00:00
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journal_title:Journal of molecular endocrinology
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journal_title:Journal of molecular endocrinology
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journal_title:Journal of molecular endocrinology
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journal_title:Journal of molecular endocrinology
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journal_title:Journal of molecular endocrinology
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abstract::Non-steroidal antioestrogens, such as tamoxifen, inhibit the growth of human breast cancer cells. The experiments described here compare and contrast the efficacy of tamoxifen and the 'pure' antioestrogen, ICI 164384, on the inhibition of proliferation of MCF-7 cells. Previous studies have shown that ICI 164384 has a ...
journal_title:Journal of molecular endocrinology
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journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
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journal_title:Journal of molecular endocrinology
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journal_title:Journal of molecular endocrinology
pub_type: 杂志文章
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journal_title:Journal of molecular endocrinology
pub_type: 历史文章,杂志文章
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journal_title:Journal of molecular endocrinology
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abstract::Fatty acids are essential nutrients that contribute to several intracellular functions. Fatty acid synthesis and oxidation are known to be regulated by sterol regulatory element-binding proteins (SREBPs), which play a pivotal role in the regulation of cellular triglyceride synthesis and cholesterol biogenesis. Recent ...
journal_title:Journal of molecular endocrinology
pub_type: 杂志文章,评审
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abstract::Synthesis of the uterine receptor for the hypothalamic hormone oxytocin has been induced in oocytes from Xenopus laevis previously primed with bovine endometrium mRNA. The injected oocytes responded to oxytocin by showing dose-dependent oscillations in membrane currents as recorded by the voltage-clamp method. The res...
journal_title:Journal of molecular endocrinology
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doi:10.1677/jme.0.0010077
更新日期:1988-07-01 00:00:00