Abstract:
:The aim of this study was to elucidate whether metformin can regulate the expression of vascular endothelial growth factor (VEGF) in rat-derived uterine leiomyoma cells (ELT-3 cells). In vitro studies were conducted using ELT-3 cells. Under normoxic conditions, metformin suppressed VEGF protein levels in the supernatant and cells in a dose-dependent manner. In hypoxia-mimicking conditions, VEGF and hypoxia-inducible factor-1α (HIF-1α) proteins were both highly expressed and were suppressed by the metformin treatment. Metformin did not affect HIF-1α mRNA levels, which indicated that its effects occurred at the post-translational level. Metformin inhibited mammalian target of rapamycin complex 1 (mTORC1) activity by phosphorylating the mTORC1 component raptor. This study revealed the anti-angiogenic activity of metformin in ELT-3 cells by suppressing the expression of VEGF via the mTORC1/HIF-1α pathway. These results indicate that metformin may represent an effective alternative in the future treatment of uterine leiomyomas.
journal_name
Mol Cell Endocrinoljournal_title
Molecular and cellular endocrinologyauthors
Tadakawa M,Takeda T,Li B,Tsuiji K,Yaegashi Ndoi
10.1016/j.mce.2014.08.012subject
Has Abstractpub_date
2015-01-05 00:00:00pages
1-8eissn
0303-7207issn
1872-8057pii
S0303-7207(14)00269-Xjournal_volume
399pub_type
杂志文章abstract::For eutherian mammals a continuum of maternal support insures that development of progeny follows an optimal program. Beginning in utero, such support extends into the early neonatal period when bioactive factors are communicated from mother to offspring in colostrum/milk. Defined as lactocrine signaling, communicatio...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章,评审
doi:10.1016/j.mce.2011.10.008
更新日期:2012-05-06 00:00:00
abstract::The effect of thyroid status on the postnatal development of the two molecular forms of Na+,K+-ATPase, distinguished kinetically on the basis of their ouabain sensitivity, was examined in rat brain. Hypothyroidism induced by PTU from day 1 postnatally significantly reduced the Na+,K+-ATPase activity in cerebellum (22-...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/0303-7207(85)90170-4
更新日期:1985-05-01 00:00:00
abstract::A macromolecular component binding 3H-labelled 17 beta-oestradiol in a specific manner and sedimenting in the 8-10-S region on sucrose gradient has been detected in the mammary gland cytosol of ovariectomized adult virgin mice. The dissociation constant of the macromolecule-oestradiol complex is 4.2 times 10(-10)M at ...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/0303-7207(76)90007-1
更新日期:1975-12-01 00:00:00
abstract::The actions of ACTH to regulate the synthesis of the various enzymes involved in steroid hormone biosynthesis have been studied using bovine adrenocortical cells in monolayer culture. ACTH causes an increase in the synthesis of both the mitochondrial and the microsomal forms of cytochrome P-450 involved in steroid hor...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章,评审
doi:10.1016/0303-7207(85)90123-6
更新日期:1985-02-01 00:00:00
abstract::Several forms of phosphodiesterase are present in the male gonad, and their relative concentrations vary during testicular development. On the basis of kinetic analysis and chromatography on DEAE cellulose, 3 forms were separated: (a) a high-affinity cGMP phosphodiesterase, regulated by Ca2+ and calmodulin, similar to...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/0303-7207(82)90039-9
更新日期:1982-09-01 00:00:00
abstract::Alternative mRNA splicing diversifies the products encoded by the NCoR and SMRT corepressor loci. There is a programmed alteration in NCoR mRNA splicing during adipocyte differentiation from an NCoRω isoform, which contains three nuclear receptor interaction domains, to an NCoRδ isoform that contains two nuclear recep...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/j.mce.2015.06.036
更新日期:2015-09-15 00:00:00
abstract::We examined the effect of growth hormone on local growth factor mRNA expression in male Sprague-Dawley rats. Repetitive systemic administration of growth hormone (0.4 IU every 4 h) increased the expression of IGF-I mRNA up to 2.8-fold in costal cartilage tissue compared with controls. Basic FGF (bFGF) mRNA expression ...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/0303-7207(95)03591-t
更新日期:1995-07-01 00:00:00
abstract::The mitochondria are critical for steroidogenesis since the ability of cholesterol to move into mitochondria to be available for cytochrome P450, CYP11A1, determines the efficacy of steroid production. Several proteins kinases, such as PKA, MEK and ERK which are essential to complete steroidogenesis, form a mitochondr...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章,评审
doi:10.1016/j.mce.2012.12.024
更新日期:2013-05-22 00:00:00
abstract::17beta-hydroxysteroid dehydrogenase type 1 (17β-HSD1) is a steroidal enzyme which, in breast cancer cells, mainly synthesizes 17-beta-estradiol (E2), an estrogenic hormone that stimulates breast cancer cell growth. We previously showed that the enzyme increased breast cancer cell proliferation via a dual effect on E2 ...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/j.mce.2016.08.026
更新日期:2017-01-05 00:00:00
abstract::Estetrol (E4) is a natural estrogen synthesized exclusively during pregnancy by the human fetal liver, and the physiological role of this hormone is unknown. Interestingly, E4 was recently evaluated in preclinical and phase II-III clinical studies in combination with a progestin, with the advantage to not increase the...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/j.mce.2018.06.010
更新日期:2018-12-05 00:00:00
abstract::Valproic acid (VPA) has been shown to increase the reprogramming efficiency of induced pluripotent stem cells (iPSC) from somatic cells, but the mechanism by which VPA enhances iPSC induction has not been defined. Here we demonstrated that VPA directly activated Oct4 promoter activity through activation of the PI3K/Ak...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/j.mce.2013.12.008
更新日期:2014-03-05 00:00:00
abstract::Estrogen plays a major role in bone mineral homeostasis, maintaining a balance between bone formation and bone resorption not only in women but also in men. Extraglandular aromatization of circulating androgen is the major source of estrogen in post-menopausal women and men. In order to assess the capacity of bone cel...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/s0303-7207(98)00069-0
更新日期:1998-04-30 00:00:00
abstract::The peculiarities of cellular and tissue distribution of prolactin receptors (PRLR) in the liver of female and male rats with different sex steroid status were investigated in paraplast-embedded tissue with the indirect immunoperoxidase technique. Two clones of antibodies directed outside the PRL-binding site (U6) or ...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/0303-7207(94)90037-x
更新日期:1994-10-01 00:00:00
abstract::Aromatase, estrone sulfatase, and 17β-hydroxysteroid dehydrogenase type 1 are involved in the key steps of 17β-estradiol biosynthesis. Structure-function studies of aromatase, estrone sulfatase and 17β-hydroxysteroid dehydrogenase type 1 are important to evaluate the molecular basis of the interaction between these en...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章,评审
doi:10.1016/j.mce.2010.09.012
更新日期:2011-07-04 00:00:00
abstract::The effect of insulin on human red blood cells was investigated, both on intact cells and on isolated plasma membranes, testing the responsiveness of membrane-bound enzymes--such as (Na+-K+)-ATPase and 5'-nucleotidase--as well as the ouabain binding and ionic fluxes. It appears that insulin stimulates Na-pumping mecha...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/0303-7207(86)90087-0
更新日期:1986-07-01 00:00:00
abstract::Accumulating evidence suggests that the human follitropin receptor is unusually sensitive to mutation. Previous results (Mol. Cell. Endo. 166 (2000) 101) determined that scanning mutations in a.a. 12-14 and 22-30 neither bound follitropin nor were present on the cell surface, suggesting that these regions are involved...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/s0303-7207(02)00424-0
更新日期:2003-03-28 00:00:00
abstract::The type 1 diabetes (T1D) risk locus on chromosome 15q25.1 harbors the candidate gene CTSH (cathepsin H). We previously demonstrated that CTSH regulates β-cell function in vitro and in vivo. CTSH overexpression protected insulin-secreting INS-1 cells against cytokine-induced apoptosis. The purpose of the present study...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/j.mce.2020.110993
更新日期:2020-12-01 00:00:00
abstract::We have shown previously that activin A increases the number of immunoreactive follicle-stimulating hormone (FSH) cells. To further investigate the action of activin A, we examined its effects on anterior pituitary cells fractionated by centrifugal elutriation. Before activin A treatment, FSH cells were widely distrib...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/0303-7207(91)90071-y
更新日期:1991-05-01 00:00:00
abstract::The molecular cloning and nucleotide sequencing of the gonadotropin-releasing hormone (GnRH) receptor represented an enhanced step in the experimental effort to understand this key molecule in the reproductive process at a cell and molecular level. A subsequent step in this broad effort is heterologous expression of t...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/s0303-7207(96)04003-8
更新日期:1997-03-28 00:00:00
abstract::We have investigated protein kinase C (PKC) regulation by 1,25-(OH)2D3 in the rat osteosarcoma cell line ROS 17/2.8 since previous reports have implicated PKC in the 1,25-(OH)2D3-mediated regulation of osteocalcin gene expression (J. Biol. Chem. 267 (1992) 12562; Endocrinology 136 (1995) 5685). Here we report that 1,2...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/s0303-7207(01)00670-0
更新日期:2002-02-25 00:00:00
abstract::The protein kinase C (PKC) activator, phorbol 12,13-dibutyrate (PDBu) induced the release of both luteinizing hormone (LH) and growth hormone (GH) from proestrous rat anterior pituitary pieces in vitro. Phorbol 12,13-dibutyrate-induced LH, but not GH release was readily inhibited by the phospholipase A2 (PLA2) inhibit...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/0303-7207(93)90031-e
更新日期:1993-09-01 00:00:00
abstract::Insulin receptor substrate-1 (IRS-1) is a protein expressed in 3T3-L1 adipocytes that is involved in most, if not all of the biological responses to insulin. Chronic exposure of these cells to insulin down-regulates IRS-1 by stimulating its degradation (Rice, K.M., Turnbow, M.A. and Garner, C.W. (1993) Biochem. Biophy...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/0303-7207(96)03875-0
更新日期:1996-08-30 00:00:00
abstract::The heterodimeric 'pregnancy-specific' hormone human chorionic gonadotropin (hCG) has been used as the basis for a contraceptive vaccine. More recently, the observation that hCG, particularly in the form of the beta-chain expressed in the absence of alpha-chain, is aberrantly expressed in a number of different tumors ...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/j.mce.2006.02.018
更新日期:2007-01-02 00:00:00
abstract::Recent evidence using GT1-7 cells indicates that GnRH pulsatility depends on exocytotic-release and gene transcription events. To determine whether calcium or DREAM may play a role in linking these processes, we used an L-type Ca(2+)-blocker (nimodipine) and found that not only GnRH gene expression (GnRH-GE) pulse act...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/j.mce.2006.12.040
更新日期:2007-03-15 00:00:00
abstract::This study examines the effect of preincubation of sheep ovarian follicles with hCG or FSH on the ability of isolated theca and granulosa to increase cAMP levels in response to a second incubation with hCG or FSH. Secondly, the effect of preincubation of small follicles with hCG on androstenedione and testosterone pro...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/0303-7207(79)90083-2
更新日期:1979-03-01 00:00:00
abstract::If human papillomavirus (HPV) is necessary for the development of (pre)neoplastic lesions of the uterine cervix, it is not sufficient. Among the cofactors involved in the malignant transformation of cells infected by HPV, sex hormones may facilitate the cervical carcinogenesis by different mechanisms, including the in...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章,评审
doi:10.1016/j.mce.2006.10.014
更新日期:2007-01-29 00:00:00
abstract::Mice carrying an RGS-insensitive Gαi2 mutation display growth retardation early after birth. Although the growth hormone (GH)-axis is a key endocrine modulator of postnatal growth, its functional state in these mice has not been characterized. The present study was undertaken to address this issue. Results revealed th...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/j.mce.2020.111098
更新日期:2021-02-05 00:00:00
abstract::There are multiple systems for cellular cholesterol delivery for steroidogenesis, including uptake of lipoprotein-derived cholesterol via LDL receptor mediated endocytic pathways and SR-BI mediated "selective" pathways, as well as from endogenous cholesterol synthesis and the mobilization of stored cholesteryl esters....
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章,评审
doi:10.1016/j.mce.2006.12.001
更新日期:2007-02-01 00:00:00
abstract::Human estrogen receptor alpha (ER) mRNA is a mixture of wild type and alternatively spliced variants. Many studies have examined the potential of ER mRNA profiles to serve as diagnostic/prognostic cancer biomarkers, but only a few have attempted to correlate ER mRNA profiles with protein expression. Representative ER ...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/s0303-7207(00)00194-5
更新日期:2000-04-25 00:00:00
abstract::Granulosa cells of small follicles differentiate in vitro in serum-free medium, resulting in increased estradiol secretion and abundance of mRNA encoding cytochrome P450aromatase (P450arom). We tested the hypothesis that differentiation in vitro also involves increased expression of 3beta- and 17beta-hydroxysteroid de...
journal_title:Molecular and cellular endocrinology
pub_type: 杂志文章
doi:10.1016/j.mce.2004.05.010
更新日期:2004-08-31 00:00:00