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Molecular and Cellular Endocrinology

Peyvand Amini, Rachel Wilson, William Koeblitz, Junye Wang, Huiqing Tan, Lijuan Yi, Zachary Stanfield, Andrea Romani, Charles Malemud, Sam Mesiano
Progesterone (P4) acting through the P4 receptor (PR) isoforms, PR-A and PR-B, promotes uterine quiescence for most of pregnancy, in part, by inhibiting the response of myometrial cells to pro-labor inflammatory stimuli. This anti-inflammatory effect is inhibited by phosphorylation of PR-A at serine-344 and -345 (pSer344/345 -PRA). Activation of the cyclic adenosine monophosphate (cAMP) signaling pathway also promotes uterine quiescence and myometrial relaxation. This study examined the cross-talk between P4/PR and cAMP signaling to exert anti-inflammatory actions and control pSer344/345 -PRA generation in myometrial cells...
August 14, 2018: Molecular and Cellular Endocrinology
Jimena S Beltrame, Micaela S Sordelli, Vanesa A Cañumil, Carlos A I Alonso, Silvina Perez Martinez, María L Ribeiro
Successful implantation and placentation requires that extravillous cytotrophoblast acquires an endovascular phenotype and remodels uterine spiral arteries. Progesterone (P4) and estradiol (E2) control many of the placental functions, but their role in vascular remodeling remains controversial. Here, we investigated whether P4 and E2 regulate the acquisition of the human first trimester trophoblast endovascular phenotype, and the participation of the lysophosphatidic acid pathway. For this purpose, human first trimester HTR-8/SVneo cells were seeded on Geltrex and assayed for capillary-like tube formation...
August 9, 2018: Molecular and Cellular Endocrinology
Ming Wu, Weixia Han, Shan Song, Yunxia Du, Chao Liu, Nan Chen, Haijiang Wu, Yonghong Shi, Huijun Duan
Diabetic nephropathy (DN) is the leading cause of end-stage renal disease. Activation of the nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome has been reported in diabetic kidney, yet the potential role of NLRP3 inflammasome in DN is not well known. In this study, we explored the role of NLRP3 inflammasome on inflammation and fibrosis in diabetic kidney using NLRP3 knockout mice. Renal expression of NLRP3, caspase-1 p10, interleukin-18 (IL-18) and cleaved IL-1β was increased in diabetic wild-type (WT) mice at 24 weeks...
August 8, 2018: Molecular and Cellular Endocrinology
Noah J Levi, Christopher W Wilson, Graham A J Redweik, Nathan W Gray, Cody W Grzybowski, Joseph A Lenkey, Anthony W Moseman, Alec D Bertsch, Nhien Dao, Heidi E Walsh
Obesity is a risk factor for infertility, but mechanisms underlying this risk are unclear. Fertility is regulated by hypothalamic gonadotropin-releasing hormone, encoded by the Gnrh1 gene. Because obesity promotes endoplasmic reticulum (ER) stress, we sought to determine how tunicamycin-induced ER stress affected Gnrh1 gene expression in the mouse hypothalamic cell line GT1-7. Tunicamycin repressed expression of Gnrh1 in a PKC- and JNK-dependent manner, while upregulating expression of a known Gnrh1 repressor, Fos...
July 29, 2018: Molecular and Cellular Endocrinology
Liang Zhao, Chenwei Wang, Melanie L Lehman, Mingyu He, Jiyuan An, Terje Svingen, Cassy M Spiller, Ee Ting Ng, Colleen C Nelson, Peter Koopman
Mammalian sex determination hinges on sexually dimorphic transcriptional programs in developing fetal gonads. A comprehensive view of these programs is crucial for understanding the normal development of fetal testes and ovaries and the etiology of human disorders of sex development (DSDs), many of which remain unexplained. Using strand-specific RNA-sequencing, we characterized the mouse fetal gonadal transcriptome from 10.5 to 13.5 days post coitum, a key time window in sex determination and gonad development...
July 24, 2018: Molecular and Cellular Endocrinology
Almas R Juma, Nathan E Hall, Joanne Wong, Jemma G Gasperoni, Yugo Watanabe, Akashdeep Sahota, Pauliina E Damdimopoulou, Sylvia V H Grommen, Bert De Groef
Knockout of pleomorphic adenoma gene 1 (PLAG1) in mice results in reduced fertility. To investigate whether PLAG1 is involved in reproductive control by the hypothalamo-pituitary system in males, we determined PLAG1 expression sites and compared gene expression between hypothalami and pituitary glands from Plag1 knockout and wildtype animals. Abundant expression of PLAG1 was detected throughout the pituitary gland, including gonadotropes and somatotropes. The hypothalamus also contained a large number of PLAG1-expressing cells...
July 24, 2018: Molecular and Cellular Endocrinology
Martine Perrot-Applanat, Martine Kolf-Clauw, Cécile Michel, Claire Beausoleil
The development and function of the mammary gland are endocrine-dependent processes, depending on the stage of development. Foetal and/or postnatal exposure to low doses of BPA alters tissue organisation through epithelial proliferation and stroma-epithelial interactions. BPA also alters the expression of E2-dependent epithelial and stroma transcriptomes. Several signalling pathways are consistent with the observed phenotype: proliferation and apoptosis, a focal adhesion pathway indicating changes in biomechanical properties of the extracellular matrix, and immune function...
July 23, 2018: Molecular and Cellular Endocrinology
Elodie P Gregoire, Isabelle Stevant, Anne-Amandine Chassot, Luc Martin, Simon Lachambre, Magali Mondin, Dirk G de Rooij, Serge Nef, Marie-Christine Chaboissier
Testis differentiation requires high levels of proliferation of progenitor cells that give rise to two cell lineages forming the testis, the Sertoli and the Leydig cells. Hence defective cell cycling leads to testicular dysgenesis that has profound effects on androgen production and fertility. The growth factor NRG1 has been implicated in adult Leydig cell proliferation, but a potential function in the fetal testis has not been analysed to date. Here we show that Nrg1 and its receptors ErbB2/3 are already expressed in early gonadal development...
July 21, 2018: Molecular and Cellular Endocrinology
María Julia Martín, Graciela Gigola, Ariel Zwenger, Martín Carriquiriborde, Florencia Gentil, Claudia Gentili
Although PTHrP is implicated in several cancers, its role in chemoresistance is not fully elucidated. We found that in CRC cells, PTHrP exerts proliferative and protective effects and induces cell migration. The aim of this work was to further study the effects of PTHrP in CRC cells. Herein we evidenced, for the first time, that PTHrP induces resistance to CPT-11 in Caco-2 and HCT116 cells; although both cell lines responded to the drug through different molecular mechanisms, the chemoresistance by PTHrP in these models is mediated through ERK, which in turn is activated by PCK, Src and Akt...
July 21, 2018: Molecular and Cellular Endocrinology
Juliana Tonietto Domingues, Carolinne Sayury Wajima, Patricia Acordi Cesconetto, Eduardo Benedetti Parisotto, Elisa Winkelmann-Duarte, Karin Dos Santos, Najla Saleh, Fabíola Branco Filippin-Monteiro, Guilherme Razzera, Fátima Regina Mena Barreto Silva, Regina Pessoa-Pureur, Ariane Zamoner
In this study, we used an experimental model of congenital hypothyroidism to show that deficient thyroid hormones (TH) disrupt different neurochemical, morphological and functional aspects in the cerebral cortex of 15-day-old offspring. Our results showing decreased glutamine synthetase (GS) activity and Ca2+ overload in the cerebral cortex of hypothyroid pups suggest misregulated glutamate metabolism associated with developmentally induced TH deficiency. The 14 C-MeAIB accumulation indicates upregulated System A activity and glutamine uptake by neurons...
July 18, 2018: Molecular and Cellular Endocrinology
Paula Bargi-Souza, Francemilson Goulart-Silva, Maria Tereza Nunes
Rapid actions of triiodothyronine (T3) on thyrotropin (TSH) synthesis and secretion have been described in hypothyroid male rats. However, the molecular mechanisms remain unknown. TαT1 cells, a thyrotroph cell line, was used herein to characterize the possible non-genomic actions of T3 on the expression of alpha (Cga) and Tshb genes, and the posttranscriptional processing and translation of both transcripts. The involvement of αVβ3 integrin was also assessed. T3 quickly reduced Tshb mRNA content, poly(A) tail length and its association with ribosomes...
July 18, 2018: Molecular and Cellular Endocrinology
Kai Jin, Lunliang Ruan, Jiujun Pu, Ailing Zhong, Fuchao Wang, Song Tan, Hua Huang, Jiamin Mu, Gang Yang
Pituitary corticotroph tumors lead to excess adrenocorticotrophic hormone (ACTH) secretion, resulting in Cushing's disease (CD), which is associated with significant mortality. Standard treatments include neurosurgery, radiotherapy and medical therapy. Both surgery and radiotherapy have undesirable complications and high recurrence rates. At present, there is only one medical option available that targets pituitary adenoma and ACTH secretion, the drug pasireotide. However, hyperglycemia is common during pasireotide treatment...
July 17, 2018: Molecular and Cellular Endocrinology
Trevor M Penning
Aldo-Keto-Reductase 1C3 (type 5 17β-hydroxysteroid dehydrogenase (HSD)/prostaglandin (PG) F2α synthase) is the only 17β-HSD that is not a short-chain dehydrogenase/reductase. By acting as a 17-ketosteroid reductase, AKR1C3 produces potent androgens in peripheral tissues which activate the androgen receptor (AR) or act as substrates for aromatase. AKR1C3 is implicated in the production of androgens in castration-resistant prostate cancer (CRPC) and polycystic ovarian syndrome; and is implicated in the production of aromatase substrates in breast cancer...
July 13, 2018: Molecular and Cellular Endocrinology
Rayane Mendes de Lima, Laura Raniere Borges Dos Anjos, Thales Biffe Alves, Alexandre Siqueira Guedes Coelho, Gustavo Rodrigues Pedrino, Rodrigo da Silva Santos, Aline Helena da Silva Cruz, Angela Adamski da Silva Reis
Diabetic patients often develop Diabetic Nephropathy (DN) despite severe long-lasting hyperglycemia, while others develop DN even under intensive insulin therapy. This indicates that factors other than chronic hyperglycemia may also contribute to the susceptibility to the development of DN. The purpose of this case-control study was to investigate the possible role of GSTM1 and GSTT1 deletion polymorphisms, and Single Nucleotide Polymorphism (SNP), GSTP1 313 A > G (Ile105Val), in DN susceptibility. Multiple logistic regression analysis revealed that the occurrence of GST polymorphisms in the Central Brazilian population was not associated with increased risk of DN...
July 5, 2018: Molecular and Cellular Endocrinology
Latha M Malaiyandi, Harsh Sharthiya, Nuntida Surachaicharn, Yara Shams, Mohammad Arshad, Chad Schupbach, Phillip G Kopf, Kirk E Dineley
A previous body of work in bovine and rodent models shows that cholinergic agonists modulate the secretion of steroid hormones from the adrenal cortex. In this study we used live-cell Ca2+ imaging to investigate cholinergic activity in the HAC15 human adrenocortical carcinoma cell line. The cholinergic agonists carbachol and acetylcholine triggered heterogeneous Ca2+ oscillations that were strongly inhibited by antagonists with high affinity for the M3 muscarinic receptor subtype, while preferential block of M1 or M2 receptors was less effective...
June 28, 2018: Molecular and Cellular Endocrinology
Rebecca J Bollinger, Laura V Ellis, Maryline C Bossus, Christian K Tipsmark
In some freshwater fish species, the control of gill Na, Cl cotransporter (Ncc2b) by prolactin appears to be instrumental to ionic homeostasis. This study was carried out to examine the signaling pathways involved in prolactin-mediated salt retention using gill explants from Japanese medaka (Oryzias latipes). Ovine prolactin induced a concentration-dependent stimulation of ncc2b with significant effects of 10, 100 and 1000 ng of hormone per mL media (2-6 fold). To understand the molecular mechanisms mediating prolactin control of gill function, we analyzed effects on signaling pathways known to be involved in the hormones action in other systems, namely Stat5, Akt and Erk1/2...
June 28, 2018: Molecular and Cellular Endocrinology
Yao Gao, Yan Cao, Xianwei Cui, Xingyun Wang, Yahui Zhou, Fangyan Huang, Xing Wang, Juan Wen, Kaipeng Xie, Pengfei Xu, Xirong Guo, Lianghui You, Chenbo Ji
Recent discoveries of functional brown adipocytes in mammals illuminates their therapeutic potential for combating obesity and its associated diseases. However, on account of the limited amount and activity in adult humans of brown adipocyte depots, identification of miRNAs and characterization their regulatory roles in human brown adipogenesis are urgently needed. This study focused on the role of microRNA (miR)-199a-3p in human brown adipocyte differentiation and thermogenic capacity. A decreased expression pattern of miR-199a-3p was consistently observed during the differentiation course of brown adipocytes in mice and humans...
June 27, 2018: Molecular and Cellular Endocrinology
Magdalena Meyer, Ilona Berger, Julia Winter, Benjamin Jurek
Oxytocin (OT) has gained attention not only as anxiolytic drug and as potential treatment option for autistic children; it also acts as a growth and differentiation factor in neuronal cells. While behavioral effects of OT have been studied in detail, knowledge about the cellular effects of OT is relatively sparse. In this study, we present evidence for three hypotheses: 1) OT leads to neurite retraction in hypothalamic neurons via the OT receptor (OTR) 2) The transcription factor MEF-2A is a central regulator of OT-induced neurite retraction, and 3) The MAPK pathway is critical for OT-induced MEF-2A activation...
June 19, 2018: Molecular and Cellular Endocrinology
Marie-Cécile Valéra, Emmanuelle Noirrit-Esclassan, Marion Dupuis, Coralie Fontaine, Françoise Lenfant, Anne Briaux, Cendrine Cabou, Cedric Garcia, Olivier Lairez, Jean-Michel Foidart, Bernard Payrastre, Jean-François Arnal
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 circulating level of coagulation factors, at variance to oral estradiol or ethinylestradiol. Here, we evaluated the effect of E4 on hemostasis and thrombosis in mouse. Following chronic E4 treatment, mice exhibited a prolonged tail-bleeding time and were protected from arterial and also venous thrombosis in vivo...
June 19, 2018: Molecular and Cellular Endocrinology
I Savchuk, M L Morvan, J P Antignac, K Gemzell-Danielsson, B Le Bizec, O Söder, K Svechnikov
It is generally accepted that androgens produced by fetal Leydig cells (FLC) control proper masculinization of the male external genitalia. Here, we hypothesized that the human genital tubercle (GT) has potential to synthesize androgens independently of FLC at early pregnancy. We observed that human GT of both genders have capacity to synthesize steroids of the Δ4 , Δ5 and alternative pathway of DHT synthesis including the androgen itself. The presence of steroids in the GT was associated with the expression of corresponding steroidogenic enzymes...
June 19, 2018: Molecular and Cellular Endocrinology
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