Androgen receptor SUMOylation regulates bone mass in male mice.


:The crucial effects of androgens on the male skeleton are at least partly mediated via the androgen receptor (AR). In addition to hormone binding, the AR activity is regulated by post-translational modifications, including SUMOylation. SUMOylation is a reversible modification in which Small Ubiquitin-related MOdifier proteins (SUMOs) are attached to the AR and thereby regulate the activity of the AR and change its interactions with other proteins. To elucidate the importance of SUMOylation of AR for male bone metabolism, we used a mouse model devoid of the two AR SUMOylation sites (ARSUM-; K381R and K500R are substituted). Six-month-old male ARSUM- mice displayed significantly reduced trabecular bone volume fraction in the distal metaphyseal region of femur compared with wild type (WT) mice (BV/TV, -19.1 ± 4.9%, P < 0.05). The number of osteoblasts per bone perimeter was substantially reduced (-60.5 ± 7.2%, P < 0.001) while no significant effect was observed on the number of osteoclasts in the trabecular bone of male ARSUM- mice. Dynamic histomorphometric analysis of trabecular bone revealed a reduced bone formation rate (-32.6 ± 7.4%, P < 0.05) as a result of reduced mineralizing surface per bone surface in ARSUM- mice compared with WT mice (-24.3 ± 3.6%, P < 0.001). Furthermore, cortical bone thickness in the diaphyseal region of femur was reduced in male ARSUM- mice compared with WT mice (-7.3 ± 2.0%, P < 0.05). In conclusion, mice devoid of AR SUMOylation have reduced trabecular bone mass as a result of reduced bone formation. We propose that therapies enhancing AR SUMOylation might result in bone-specific anabolic effects with minimal adverse effects in other tissues.


Mol Cell Endocrinol


Wu J,Movérare-Skrtic S,Zhang FP,Koskela A,Tuukkanen J,Palvimo JJ,Sipilä P,Poutanen M,Ohlsson C




Has Abstract


2019-01-05 00:00:00












  • 1,25-Dihydroxyvitamin D3 selectively translocates PKCalpha to nuclei in ROS 17/2.8 cells.

    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


    authors: Rivera-Bermúdez MA,Bertics PJ,Albrecht RM,Mosavin R,Mellon WS

    更新日期:2002-02-25 00:00:00

  • Vitamin A modulates the effects of thyroid hormone on UDP-glucuronosyltransferase expression and activity in rat liver.

    abstract::We studied the influence of thyroid hormones and vitamin A status on the regulation of UDP-glucuronosyltransferase (UGT) expression and the glucuronidation of thyroid hormones by UGTs. For this, we used an original model of rats fed with different vitamin A diets and implanted subcutaneously by osmotic minipumps deliv...

    journal_title:Molecular and cellular endocrinology

    pub_type: 杂志文章


    authors: Haberkorn V,Heydel JM,Mounie J,Artur Y,Goudonnet H

    更新日期:2002-04-25 00:00:00

  • Transcript profiles and triiodothyronine regulation of sex steroid- and thyroid hormone-related genes in the gonad-mesonephros complex of Silurana tropicalis.

    abstract::In amphibians, the main role of thyroid hormones (THs) is to regulate metamorphosis; however, there is evidence that THs also affect gonadal sexual differentiation. In this study, Silurana (Xenopus) tropicalis tadpoles were exposed to triiodothyronine (T3; 0, 0.5, 5 and 50 nM), the bioactive form of THs for 48h. Real-...

    journal_title:Molecular and cellular endocrinology

    pub_type: 杂志文章


    authors: Duarte-Guterman P,Trudeau VL

    更新日期:2011-01-01 00:00:00

  • Regulation of the mouse mammary tumor virus (MMTV) binding site in cultured mammary tissue.

    abstract::The mouse mammary tumor virus (MMTV) initiates infection when the envelope protein, gp52, binds to a cell surface protein and triggers internalization. The hormonal regulation of this protein was studied both in vitro and in vivo. In mammary gland explant culture, levels of the MMTV binding protein were maintained onl...

    journal_title:Molecular and cellular endocrinology

    pub_type: 杂志文章


    authors: Bolander FF Jr

    更新日期:1991-12-01 00:00:00

  • Bioactive forms of vitamin D selectively stimulate the skin analog of the hypothalamus-pituitary-adrenal axis in human epidermal keratinocytes.

    abstract::Ultraviolet radiation B stimulates both the production of vitamin D3 in the skin and the activation of the skin analog of the hypothalamic-pituitary-adrenal axis (HPA) as well as the central HPA. Since the role of vitamin D3 in the regulation of the HPA is largely unknown, we investigated the impact of 1,25(OH)2D3 and...

    journal_title:Molecular and cellular endocrinology

    pub_type: 杂志文章


    authors: Wierzbicka JM,Żmijewski MA,Piotrowska A,Nedoszytko B,Lange M,Tuckey RC,Slominski AT

    更新日期:2016-12-05 00:00:00

  • Characterization and regulation of a mRNA encoding the prostaglandin F2alpha receptor in the rat ovary.

    abstract::The recent cloning of several cDNAs encoding prostaglandin (PG) receptors has paved the way for a more detailed investigation of the postulated regulatory role of prostaglandins in corpus luteum function. We have utilized the reverse transcription-polymerase chain reaction (RT-PCR) to isolate a mRNA encoding the ovari...

    journal_title:Molecular and cellular endocrinology

    pub_type: 杂志文章


    authors: Olofsson JI,Leung CH,Bjurulf E,Ohno T,Selstam G,Peng C,Leung PC

    更新日期:1996-10-14 00:00:00

  • Effect of glutathione redox state on Leydig cell susceptibility to acute oxidative stress.

    abstract::The free radical, or oxidative stress, theory posits that imbalance in cells between prooxidants and antioxidants results in an altered redox state and, over time, an accumulation of oxidative damage. We hypothesized herein that cells with an increasingly prooxidant intracellular environment also might be particularly...

    journal_title:Molecular and cellular endocrinology

    pub_type: 杂志文章


    authors: Chen H,Zhou L,Lin CY,Beattie MC,Liu J,Zirkin BR

    更新日期:2010-07-29 00:00:00

  • Relaxin-like factor (RLF) mRNA expression in the fallow deer.

    abstract::Employing RT- and RACE-PCR on RNA isolated from testicular tissue, we have cloned the coding cDNA sequence for the RLF, also known as Insl3, of the fallow deer. The RLF coding sequence consisted of 396 bp encoding a peptide of 131 amino acids and shared highest homology with bovine, sheep and goat RLF. Northern analys...

    journal_title:Molecular and cellular endocrinology

    pub_type: 杂志文章


    authors: Hombach-Klonisch S,Kauffold J,Rautenberg T,Steger K,Tetens F,Fischer B,Klonisch T

    更新日期:2000-01-25 00:00:00

  • Identification and characterization of the glucagon receptor from adipose tissue.

    abstract::125I-glucagon was directly cross-linked to its receptor in isolated adipocyte plasma membranes using a UV irradiation procedure. This investigation resulted in identification of an adipocyte glucagon receptor complex of 62 kDa, present both in white and brown adipose tissues. The specificity of labeling was shown by i...

    journal_title:Molecular and cellular endocrinology

    pub_type: 杂志文章


    authors: Iwanij V,Amos TM,Billington CJ

    更新日期:1994-05-01 00:00:00

  • A selective biotinylated probe for V1a vasopressin receptors.

    abstract::We have designed and synthesized a biotinylated vasopressin antagonist which is a selective probe for studying the V1a subtype of vasopressin receptor. Initially we synthesized the novel vasopressin analogue d(CH2)5Tyr(Me)2LysNH2(9)AVP (ALVP). Biotinamidocaproate was subsequently coupled to the epsilon-amino group of ...

    journal_title:Molecular and cellular endocrinology

    pub_type: 杂志文章


    authors: Howl J,Kerr ID,Chan CH,Wheatley M

    更新日期:1991-05-01 00:00:00

  • Plasminogen activator inhibitor-1 expression and secretion are stimulated by growth hormone and interleukin-6 in 3T3-L1 adipocytes.

    abstract::Various adipocytokines have been described which influence insulin sensitivity and vascular function profoundly and might, therefore, potentially link obesity, insulin resistance, and atherosclerosis. Among those, plasminogen activator inhibitor (PAI)-1 is an adipose-secreted factor upregulated in obesity and insulin ...

    journal_title:Molecular and cellular endocrinology

    pub_type: 杂志文章


    authors: Kralisch S,Klein J,Lossner U,Blüher M,Paschke R,Stumvoll M,Fasshauer M

    更新日期:2006-07-11 00:00:00

  • Mammary Stat5 abundance and activity are not altered with lactation state in cows.

    abstract::Stat5 is a key intracellular mediator of prolactin signalling and can activate transcription of milk proteins in response to prolactin. Therefore, in animals such as mice where lactation is dependent on prolactin, Stat5 is likely to play an important role in establishing or maintaining lactation in the mammary gland. ...

    journal_title:Molecular and cellular endocrinology

    pub_type: 杂志文章


    authors: Wheeler TT,Kuys YM,Broadhurst MM,Molenaar AJ

    更新日期:1997-10-20 00:00:00

  • Effects of thyroidectomy on heart and liver rat tRNAs: study of chromatographic and electrophoretic behaviour.

    abstract::Modifications of tRNAs in various physiological or experimental conditions are well documented. We have compared isoacceptor tRNAs extracted from target organs (heart and liver) from thyroidectomized rats to those of control animals. Nine liver aminoacyl-tRNAs and eight heart aminoacyl-tRNAs from thyroidectomized and ...

    journal_title:Molecular and cellular endocrinology

    pub_type: 杂志文章


    authors: Kessous C,Befort JJ,Befort N,Benmiloud M

    更新日期:1983-02-01 00:00:00

  • Concentration of activin A and follistatin in follicular fluid from human small antral follicles associated to gene expression of the corresponding granulosa cells.

    abstract::The present study correlated concentrations of activin A and follistatin in follicular fluid (FF) from human small antral follicles to FF concentrations of AMH, inhibin B, progesterone, and oestradiol and to the mRNA expression of FSH-receptor (FSHR), LH-receptor (LHR), AMH-receptor2 (AMHR2), CYP19a, and androgen-rece...

    journal_title:Molecular and cellular endocrinology

    pub_type: 杂志文章


    authors: Jeppesen JV,Nielsen ME,Kristensen SG,Yding Andersen C

    更新日期:2012-06-05 00:00:00

  • Differential impact of oleate, palmitate, and adipokines on expression of NF-κB target genes in human vascular smooth muscle cells.

    abstract::It is widely accepted that obesity is a major risk factor for the development of atherosclerosis. In this context, adipose tissue produces a variety of adipokines and releases free fatty acids, contributing to a chronic-low grade inflammation state implicated in vascular complications. In this study, we investigated t...

    journal_title:Molecular and cellular endocrinology

    pub_type: 杂志文章


    authors: Lamers D,Schlich R,Horrighs A,Cramer A,Sell H,Eckel J

    更新日期:2012-10-15 00:00:00

  • The control of liver regeneration by calcitonin, parathyroid hormone and 1 alpha,25-dihydroxycholecalciferol.

    abstract::Removal of the thyroid in normocalcemic rats with functional parathyroid transplants was found to reduce the hepatocyte DNA synthetic activity which normally follows partial hepatectomy. This proliferative incapacitation of hepatocytes appeared to be due specifically to a calcitonin deficiency since it was overcome by...

    journal_title:Molecular and cellular endocrinology

    pub_type: 杂志文章


    authors: Rixon RH,MacManus JP,Whitfield JF

    更新日期:1979-08-01 00:00:00

  • A putative role for endogenous FGF-2 in FGF-1 mediated differentiation of human preadipocytes.

    abstract::The defining characteristic of obesity is increased adipose tissue (AT) mass following chronic positive energy supply. AT mass is determined by adipocyte number and size, which reflect proliferation and differentiation of preadipocytes and hypertrophy of pre-existing adipocytes. The molecular pathways governing AT exp...

    journal_title:Molecular and cellular endocrinology

    pub_type: 杂志文章


    authors: Hutley LJ,Newell FS,Kim YH,Luo X,Widberg CH,Shurety W,Prins JB,Whitehead JP

    更新日期:2011-06-06 00:00:00

  • Estrogen receptor development in the absence of growth hormone and prolactin: studies in dwarf mice.

    abstract::The concentration of high-affinity estradiol binding sites in the uteri and pituitaries of normal and two dwarf strains of mice was studied. The two dwarf strains are characterized by their total absence of growth hormone or prolactin synthesis and low or absent TSH production. The uteri of the dwarf mice are small bu...

    journal_title:Molecular and cellular endocrinology

    pub_type: 杂志文章


    authors: Sartor P,Slabaugh M,Sakai D,Gorski J

    更新日期:1983-01-01 00:00:00

  • The role of estrogen in folliculogenesis.

    abstract::Gonadotrophins are fundamental to the mechanisms regulating follicle status and development. Follicles in the ovary are either quiescent or committed to one of two pathways: growth or atresia. The requirement for gonadotrophins by the follicles varies with development: committed follicles grow independently of gonadot...

    journal_title:Molecular and cellular endocrinology

    pub_type: 杂志文章,评审


    authors: Drummond AE,Findlay JK

    更新日期:1999-05-25 00:00:00

  • Differential regulation of corticotropin-releasing factor receptor type 1 (CRF1 receptor) mRNA via protein kinase A and mitogen-activated protein kinase pathways in rat anterior pituitary cells.

    abstract::Corticotropin-releasing factor (CRF) receptor type 1 (CRF(1) receptor) mRNA levels are down-regulated by CRF via the cyclic AMP-protein kinase A (PKA) pathway. In this study, we focused on the involvement of both the mitogen-activated protein (MAP) kinase pathway and PKA in this regulation. Real-time PCR (RT-PCR) reve...

    journal_title:Molecular and cellular endocrinology

    pub_type: 杂志文章


    authors: Moriyama T,Kageyama K,Kasagi Y,Iwasaki Y,Nigawara T,Sakihara S,Suda T

    更新日期:2005-11-24 00:00:00

  • Understanding primary aldosteronism: impact of next generation sequencing and expression profiling.

    abstract::Primary aldosteronism (PA) encompasses a broad, heterogeneous group of disorders including both sporadic and familial forms (familial hyperaldosteronism type I, II and III). PA is the most common form of secondary hypertension and associated with a higher rate of cardiovascular complications, compared with essential h...

    journal_title:Molecular and cellular endocrinology

    pub_type: 杂志文章,评审


    authors: Monticone S,Else T,Mulatero P,Williams TA,Rainey WE

    更新日期:2015-01-05 00:00:00

  • Rapid responses to thyroxine in the testis: active protein synthesis-independent pathway.

    abstract::We investigated the involvement of protein synthesis in the stimulatory action of thyroid hormones on amino acid accumulation and characterized K(+) currents involved in the hyperpolarizing effect of thyroxine (T(4)) on Sertoli cells. Immature rat testes were incubated in Krebs Ringer-bicarbonate buffer (KRb) in the p...

    journal_title:Molecular and cellular endocrinology

    pub_type: 杂志文章


    authors: Menegaz D,Zamoner A,Royer C,Leite LD,Bortolotto ZA,Silva FR

    更新日期:2006-02-26 00:00:00

  • Cytochrome P-450 and the aromatization of 16alpha-hydroxytestosterone and androstenedione by human placental microsomes.

    abstract::When measured in vitro using human placental microsomal preparations, the aromatization of 16alpha-hydroxytestosterone to estriol and androstenedione to estrone and estradiol proceeds at almost identical initial rates. Important differences between 16alpha-hydroxytestosterone and adrostenedione aromatization are evide...

    journal_title:Molecular and cellular endocrinology

    pub_type: 杂志文章


    authors: Canick JA,Ryan KJ

    更新日期:1976-12-01 00:00:00

  • Oxytocin mRNA: increase of polyadenylate tail size during pregnancy and lactation.

    abstract::Earlier studies indicate that rat hypothalamic oxytocin (OT) mRNA accumulation rises gradually during pregnancy and remains elevated throughout the lactation period. Here we show that, in addition, hypothalamic OT mRNA undergoes a structural change during this period. On gel electrophoresis, the size of rat OT mRNA in...

    journal_title:Molecular and cellular endocrinology

    pub_type: 杂志文章


    authors: Zingg HH,Lefebvre DL

    更新日期:1989-08-01 00:00:00

  • Roles of gonadotropins and meiosis-activating sterols in meiotic resumption of cultured follicle-enclosed mouse oocytes.

    abstract::This study describes a model for short-term culture of intact mouse follicles under serum-free conditions. Follicles were either obtained from immature mice receiving no ovarian stimulation (i.e. no eCG-primed protocol, group I) or from mice undergoing ovarian stimulation (i.e. eCG-primed protocol, group II). Follicle...

    journal_title:Molecular and cellular endocrinology

    pub_type: 杂志文章


    authors: Xie H,Xia G,Byskov AG,Andersen CY,Bo S,Tao Y

    更新日期:2004-04-15 00:00:00

  • Specific transgene expression in mouse pancreatic beta-cells under the control of the porcine insulin promoter.

    abstract::The availability of regulatory sequences directing tissue-specific expression of transgenes in genetically modified mice and large animals is a prerequisite for the development of adequate models for human diseases. The rat insulin 2 gene (Ins2) promoter, widely used to achieve transgene expression in pancreatic beta-...

    journal_title:Molecular and cellular endocrinology

    pub_type: 杂志文章


    authors: Grzech M,Dahlhoff M,Herbach N,Habermann FA,Renner-Müller I,Wanke R,Flaswinkel H,Wolf E,Schneider MR

    更新日期:2010-02-05 00:00:00

  • Expression of adrenocortical steroidogenic acute regulatory (StAR) protein is influenced by chromaffin cells.

    abstract::Cell-cell interactions are crucial role for the proper functioning of endocrine glands. We recently demonstrated that interactions of chromaffin and cortical cells are important for adrenocortical steroidogenesis. However, the molecular mechanisms have not been elucidated and it is unclear if this involves acute and/o...

    journal_title:Molecular and cellular endocrinology

    pub_type: 杂志文章


    authors: Haidan A,Bornstein SR,Liu Z,Walsh LP,Stocco DM,Ehrhart-Bornstein M

    更新日期:2000-07-25 00:00:00

  • Fasting modulates GH/IGF-I axis and its regulatory systems in the mammary gland of female mice: Influence of endogenous cortistatin.

    abstract::Growth hormone (GH) and insulin-like growth factor-I (IGF-I) are essential factors in mammary-gland (MG) development and are altered during fasting. However, no studies have investigated the alterations in the expression of GH/IGF-I and its regulatory systems (somatostatin/cortistatin and ghrelin) in MG during fasting...

    journal_title:Molecular and cellular endocrinology

    pub_type: 杂志文章


    authors: Villa-Osaba A,Gahete MD,Cordoba-Chacon J,de Lecea L,Castaño JP,Luque RM

    更新日期:2016-10-15 00:00:00

  • Administration of growth hormone modulates the gene expression of basic fibroblast growth factor in rat costal cartilage, both in vivo and in vitro.

    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


    authors: Izumi T,Shida J,Jingushi S,Hotokebuchi T,Sugioka Y

    更新日期:1995-07-01 00:00:00

  • Estrogen receptor mutations.

    abstract::The purpose of this paper is to review potential novel functional pathways by which estradiol and estrogenic compounds elicit biological responses in mammals. We will limit our approach to those novel functions suggested by phenotypes associated with estrogen receptor-alpha (ER alpha) gene mutations and polymorphisms....

    journal_title:Molecular and cellular endocrinology

    pub_type: 杂志文章,评审


    authors: Taylor JA,Lewis KJ,Lubahn DB

    更新日期:1998-10-25 00:00:00