Armando Ribeiro Florido Neto, Lucas Agostini, Luciano Pedro da Silva Junior, Maria Tereza Nunes
Alloxan-induced diabetic rats present hypothyroidism. When treated with triiodothyronine (T3), glycaemia and pro-inflammatory cytokine expression are downregulated, improving insulin sensitivity. The effectiveness of associating T3 with insulin [replacement dose (6U) and (3U)] in controlling glycaemia was investigated in this experimental model. Male Wistar rats were made diabetic by alloxan injection and sorted into groups treated or not with insulin (3 or 6U) associated or not with T3 (1.5 µg 100 g-1 BW) for 28 days...
June 12, 2024: Endocrinology
Guanliang Chen, Yanwen Yu, Yuqin Zhu, Mayumi Nagashimada, Yajiao Wang, Naoto Nagata, Liang Xu
The inhibition of hepatic macrophage and Kupfer cell recruitment and activation is a potential strategy for treating insulin resistance and nonalcoholic steatohepatitis (NASH). Cenicriviroc (CVC), a dual C-C chemokine receptor 2 (CCR2) and CCR5 antagonist, has shown anti-fibrotic activity in murine models of NASH and has been evaluated in clinical trials on patients with NASH. This study investigated the effects of CVC on macrophage infiltration and polarization in a lipotoxic model of NASH. C57BL/6 mice were fed a high-cholesterol, high-fat (CL) diet or a CL diet containing 0...
June 12, 2024: Endocrinology
Guilherme Gabriel de Almeida, Anaysa P Bolin, Alice Batistuzzo, Tatiana Fonseca, Miriam O Ribero, Antonio C Bianco
About half of the world population carries at least one allele of the Ala92-DIO2, which slows down the activity of the type 2 deiodinase (D2), the enzyme that activates T4 to T3. Carrying the Ala92-DIO2 allele has been associated with increased BMI and insulin resistance, but this has not been reproduced in all populations. To test if the genetic background affects the impact of this polymorphism, here we studied the genetically distant C57Bl/6J (B6) and FVB/N (FVB) mice carrying the Ala92-Dio2 allele as compared to control mice carrying the Thr92-Dio2 allele...
June 5, 2024: Endocrinology
Hailan Liu, Zhaoxun Liu, HueyXian Kelly Wong, Nathan Xu, Qingzhuo Liu, Yongxiang Li, Yao Liu, Huey Zhong Wong, Megan E Burt, Sanika V Jossy, Junying Han, Yang He
The serotonin 2C receptor (5-HT2CR)-melanocortin pathway plays well-established roles in the regulation of feeding behavior and body weight homeostasis. Dysfunctions in this system, such as loss-of-function mutations in the Htr2c gene, can lead to hyperphagia and obesity. In this study, we aimed to investigate the potential therapeutic strategies for ameliorating hyperphagia, hyperglycemia and obesity associated with a loss-of-function mutation in the Htr2c gene (Htr2cF327L/Y). We demonstrated that re-expressing functional 5-HT2CR solely in hypothalamic pro-opiomelanocortin (POMC) neurons is sufficient to reduce food intake and body weight in Htr2cF327L/Y mice subjected to a high-fat diet...
May 30, 2024: Endocrinology
María Paula Cornejo, Gimena Fernandez, Agustina Cabral, Franco Barrile, Florencia Heredia, Guadalupe García Romero, Juan Pablo Zubimendi Sampieri, Juan Ignacio Quelas, Sonia Cantel, Jean-Alain Fehrentz, Antonia Alonso, Ramon Pla, José Luis Ferran, María Florencia Andreoli, Pablo Nicolas De Francesco, Mario Perelló
The growth hormone secretagogue receptor (GHSR), primarily known as the receptor for the hunger hormone ghrelin, potently controls food intake, yet the specific Ghsr-expressing cells mediating the orexigenic effects of this receptor remain incompletely characterized. Since Ghsr is expressed in gamma-aminobutyric acid-producing neurons (GABA neurons), we sought to investigate whether the selective expression of Ghsr in a subset of GABA neurons is sufficient to mediate GHSR's effects on feeding. First, we crossed mice that express a tamoxifen-dependent Cre recombinase in the subset of GABA neurons that express glutamic acid decarboxylase 2 (Gad2) enzyme (Gad2-CreER mice) with reporter mice, and found that ghrelin mainly targets a subset of Gad2-expressing neurons located in the hypothalamic arcuate nucleus (ARH) and that is predominantly segregated from Agouti-related protein (AgRP)-expressing neurons...
May 30, 2024: Endocrinology
Zhongmin Li, Clara Wenhart, Andreas Reimann, Silvia Goebel, Yi-Li Cho, Goetz Muench
The thyroid in Graves' disease undergoes a considerable divergence in size and position from the normal anatomy. However, knowledge of the pathological anatomy related to the change, which is required before planned surgical or local intervention, or diagnosis, is neglected. To investigate Graves' disease, we well-established a model of mice that successfully mimics all the signs presented in the clinic. Under a long-term immunization (35 weeks), the animals displayed a big heterogeneity in thyroid size, like the cases of natural occurrence...
May 24, 2024: Endocrinology
Irene E Sucquart, Chris Coyle, Valentina Rodriguez Paris, Melanie Prescott, Kelly A Glendining, Kyoko Potapov, Denovan P Begg, Robert B Gilchrist, Kirsty A Walters, Rebecca E Campbell
Androgen excess is a hallmark feature of polycystic ovary syndrome (PCOS), the most common form of anovulatory infertility. Clinical and preclinical evidence links developmental or chronic exposure to hyperandrogenism with programming and evoking the reproductive and metabolic traits of PCOS. While critical androgen targets remain to be determined, central GABAergic neurons are postulated to be involved. Here, we tested the hypothesis that androgen signalling in GABAergic neurons is critical in PCOS pathogenesis in two well-characterised hyperandrogenic mouse models of PCOS...
May 23, 2024: Endocrinology
Ryota Tanida, Hisanori Goto, Hiroaki Takayama, Yujiro Nakano, Hein Ko Oo, Cynthia Monserrat Galicia-Medina, Kenta Takahashi, Kiyo-Aki Ishii, Arman Syah Goli, Takashi Matsuzaka, Kenichi Harada, Toshinari Takamura
Leukocyte cell-derived chemotaxin 2 (LECT2) is a protein initially isolated as a neutrophil chemotactic factor. We previously found that LECT2 is an obesity-associated hepatokine that senses liver fat and induces skeletal muscle insulin resistance. In addition, hepatocyte-derived LECT2 activates macrophage pro-inflammatory activity by reinforcing the LPS-induced c-Jun N-terminal kinase (JNK) signaling. Based on these findings, we examined the impact of LECT2 deletion on NAFLD/NASH caused by bacterial translocation...
May 23, 2024: Endocrinology
Takuro Hakata, Yohei Ueda, Takafumi Yamashita, Ichiro Yamauchi, Daisuke Kosugi, Taku Sugawa, Haruka Fujita, Kentaro Okamoto, Toshihito Fujii, Daisuke Taura, Akihiro Yasoda, Haruhiko Akiyama, Nobuya Inagaki
C-type natriuretic peptide (CNP) plays a crucial role in enhancing endochondral bone growth and holds promise as a therapeutic agent for impaired skeletal growth. To overcome CNP's short half-life, we explored the potential of dampening its clearance system. Neprilysin (NEP) is an endopeptidase responsible for catalyzing the degradation of CNP. Thus, we investigated the effects of NEP inhibition on skeletal growth by administering sacubitril, a NEP inhibitor, to C57BL/6 mice. Remarkably, we observed a dose-dependent skeletal overgrowth phenotype in mice treated with sacubitril...
May 16, 2024: Endocrinology
Tingjie Zhan, Jiyang Zhang, Ying Zhang, Qingshi Zhao, Anat Chemerinski, Nataki C Douglas, Qiang Zhang, Shuo Xiao
Follicle-stimulating hormone (FSH) binds to its membrane receptor (FSHR) in granulosa cells to activate various signal transduction pathways and drive the gonadotropin-dependent phase of folliculogenesis. Poor female reproductive outcomes can result from both FSH insufficiency owing to genetic or non-genetic factors and FSH excess as encountered with ovarian stimulation in assisted reproductive technology (ART), but the underlying molecular mechanisms remain elusive. Herein, we conducted single-follicle and single-oocyte RNA sequencing analysis along with other approaches in an ex vivo mouse folliculogenesis and oogenesis system to investigate the effects of different concentrations of FSH on key follicular events...
May 13, 2024: Endocrinology
Filipe Menezes, Frederick Wasinski, Gabriel O de Souza, Amanda P Nunes, Emerson S Bernardes, Sofia N Dos Santos, Fábio F A da Silva, Cibele N Peroni, João E Oliveira, John J Kopchick, Rosemary S E Brown, Gimena Fernandez, Pablo N De Francesco, Mario Perelló, Carlos R J Soares, Jose Donato
Growth hormone (GH) acts in numerous organs expressing the GH receptor (GHR), including the brain. However, the mechanisms behind the brain's permeability to GH and how this hormone accesses different brain regions remain unclear. It is well-known that an acute GH administration induces phosphorylation of the signal transducer and activator of transcription 5 (pSTAT5) in the mouse brain. Thus, the pattern of pSTAT5 immunoreactive cells was analyzed at different time points after intraperitoneal or intracerebroventricular GH injections...
May 10, 2024: Endocrinology
Naoe Kotomura, Yohei Shimono, Satoru Ishihara
CYP19A1 encodes aromatase, which converts testosterone to estrogen, and is induced during placental maturation. To elucidate the molecular mechanism underlying this function, histone methylation was analyzed using the placental cytotrophoblast cell line, JEG3. Treatment of JEG3 cells with 3-deazaneplanocin A, an inhibitor of several methyltransferases, resulted in increased CYP19A1 expression, accompanied by removal of the repressive mark H3K27me3 from the CYP19A1 promoter. However, this increase was not observed in cells treated with GSK126, another specific inhibitor for H3K27me3 methylation...
May 8, 2024: Endocrinology
Jamaira Aparecida Victorio, Letícia Barssotti, Tamar Aprahamian, Raul Gobato Costa, Felippe Mousovich-Neto, Helena Coutinho Franco de Oliveira, Marcelo Mori, Luciana Venturini Rossoni, Ana Paula Davel
Long-term β-adrenoceptor (β-AR) stimulation is a pathological mechanism associated with cardiovascular diseases resulting in endothelial and perivascular adipose tissue (PVAT) dysfunction. In this study, we aimed to identify whether β-adrenergic signaling has a direct effect on PVAT. Thoracic aorta PVAT was obtained from male Wistar rats and cultured ex vivo with the β-AR agonist isoproterenol (Iso; 1 µM) or vehicle for 24 hours. Conditioned culture medium (CCM) from Iso-treated PVAT induced a marked increase in aorta contractile response, induced oxidative stress and reduced nitric oxide production in PVAT compared to vehicle...
May 7, 2024: Endocrinology
Kamila Adamczuk, Thu Ha Ngo, Jakub Czapinski, Adolfo Rivero-Müller
The glycoprotein receptors, members of the large G protein-coupled receptors (GPCRs) family, are characterized by a large extracellular domains responsible of binding their glycoprotein hormones. Hormone-receptor interactions are traditionally analyzed by ligand-binding assays most often using radiolabeling but also by thermal shift assays. Despite their high sensitivity, these assays require appropriate laboratory conditions and, often, purified plasma cell membranes, which do not provide information on receptor localization or activity as these assays typically focus on measuring binding only...
April 29, 2024: Endocrinology
Yanjie Huang, Fangfang Dai, Liping Chen, Zhidian Li, Hua Liu, Yanxiang Cheng
BACKGROUND: Recurrent spontaneous abortion (RSA) is defined as the loss of two or more consecutive intrauterine pregnancies with the same sexual partner in the first trimester. Despite its significance, the etiology and underlying mechanisms of RSA remain elusive. Defective decidualization is proposed as one of the potential causes of RSA, with abnormal decidualization leading to disturbances in trophoblast invasion function. METHODS: Decidual samples were collected from both RSA patients and healthy controls to assess BMP4 expression...
April 29, 2024: Endocrinology
Yu-Ting Tiffany Chiang, Christopher D Kassotis
Hormonal contraceptives are widely prescribed due to their effectiveness and convenience and have become an integral part of family planning strategies worldwide. In the US, ∼65% of reproductive aged women are estimated to be using contraceptive options, with ∼33% using one or a combination of hormonal contraceptives. While these methods have undeniably contributed to improved reproductive health, recent studies have raised concerns regarding their potential impact on metabolic health. Despite widespread anecdotal reports, epidemiological research has been mixed as to whether hormonal contraceptives contribute to metabolic health effects...
April 22, 2024: Endocrinology
Govinda R Hancock, Jason Gertz, Rinath Jeselsohn, Sean W Fanning
Annual breast cancer (BCa) deaths have declined since its apex in 1989 concomitant with widespread adoption of hormone therapies that target estrogen receptor alpha (ERα), the prominent nuclear receptor expressed in ∼80% of BCa. However, up to ∼50% of ER + patients with high-risk disease experience post endocrine therapy relapse and metastasis to distant organs. The vast majority of BCa mortality occurs in this setting, highlighting the inadequacy of current therapies. Genomic abnormalities to ESR1, the gene encoding ERα, emerge under prolonged selective pressure to enable endocrine therapy resistance...
April 21, 2024: Endocrinology
Peck Y Chin, Tom E C Kieffer, Jelmer R Prins, Darryl L Russell, Michael J Davies, Sarah A Robertson
Clomiphene citrate is a common treatment for ovulation induction in subfertile women, but its use is associated with elevated risk of adverse perinatal outcomes and birth defects. To investigate the biological plausibility of a causal relationship, this study investigated in mice the consequences for fetal development and pregnancy outcome of peri-conception clomiphene citrate administration at doses approximating human exposures. A dose-dependent adverse effect of clomiphene citrate given twice in the 36 h after mating was seen, with a moderate dose of 0...
April 12, 2024: Endocrinology
Gabriela de Faria Oliveira, Amber T Nguyen, Leykza Carreras-Simons, Thomas Niepsuj, Salma H Gadelhak, Aimee K Johnson, Ashwakh Abdalla, Eden Lev, Sofia G Torres Román, Samantha N Fuchs, Joan S Jorgensen, Walid A Farhat, Anthony P Auger
We examined the impact of the puberty blocker, leuprolide acetate, on sex differences in juvenile rough-and-tumble play behavior and anxiety-like behavior in adolescent male and female rats. We also evaluated leuprolide treatment on gonadal and pituitary hormone levels and activity-regulated cytoskeleton-protein mRNA levels within the adolescent amygdala, a region important for both rough-and-tumble play and anxiety-like behavior. Our findings suggest that leuprolide treatment lowered anxiety-like behavior during adolescent development, suggesting that the maturation of GnRH systems may be linked to increased anxiety...
April 10, 2024: Endocrinology
Aleksandar Ivovic, Justin Hou Ming Yung, Andrei I Oprescu, Filip Vlavcheski, Yusaku Mori, S M Niazur Rahman, Wenyue Ye, Judith A Eversley, Michael B Wheeler, Minna Woo, Evangelia Tsiani, Adria Giacca
In the classical insulin target tissues liver, muscle and adipose tissue, chronically elevated levels of free fatty acids (FFA) impair insulin signaling. Insulin signaling molecules are also present in β-cells where they play a role in β-cell function. Therefore, inhibition of the insulin/IGF-1 pathway may be involved in fat-induced β-cell dysfunction. To address the role of β-cell insulin resistance in FFA-induced β-cell dysfunction we co-infused bisperoxovanadate (BPV) with oleate or olive oil for 48 h in rats...
April 5, 2024: Endocrinology
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