Archives of Endocrinology Metabolism

Prenatal exposure to nitrate alters uterine morphology and gene expression in adult female F1 generation rats
Cassiani AG, Aloia TPA, Sousa-Vidal ÉK, Podgaec S, Piccinato CA and Serrano-Nascimento C
Nitrate is ubiquitously found in the environment and is one of the main components of nitrogen fertilizers. Previous studies have shown that nitrate disrupts the reproductive system in aquatic animals, but no study has evaluated the impact of nitrate exposure on the uterus in mammals. This study aimed to evaluate the impact of maternal exposure to nitrate during the prenatal period on uterine morphology and gene expression in adult female F1 rats.
A rare case of double pituitary prolactinomas: the diagnostic application of intraoperative ultrasonography and DNA methylation markers
Reese JC, Zervos TM, Rock J, Tabbarah A, Noushmehr H, Herrgott G and Castro AV
The aim of this study is to describe the management and evolution of a patient with the rare condition of double lactotroph tumors and assess the role of intraoperative ultrasonography (IOUS) for their detection and methylation-based liquid biopsy for their diagnosis and monitoring. A 29-year-old woman diagnosed with double lactotroph tumors through hormonal and MRI workup underwent surgical resection due to cabergoline intolerance. To detect a tumor missing through visual inspection, IOUS was performed. Pituitary tumor (PT) and nontumor (NT) tissues and blood were collected for pathological and molecular assessments (genome-wide methylation level profiled using the EPIC array, at surgery and follow-up). Reference methylome data were obtained from publicly available repositories. Both tumors (T1 and T2) were detected via IOUS and confirmed as lactotroph tumors through immunohistochemistry. In tissue specimens, PT-specific markers distinguished T1 from NT tissue, while T2, primarily nontumor cells, clustered with NT specimens. In liquid biopsies, these markers differentiated between T and NT cohorts. During the 12-month follow-up, methylation profiling and prolactin blood assessments showed that methylation markers clustered with NT specimens, which coincided with prolactinemia normalization, indicating successful tumor control after surgery. This case illustrates the translational use of methylation-based liquid biopsy methodologies in detecting and monitoring PTs through the detection of tumor-specific markers in blood specimens. This approach can be useful to distinguish sellar masses mimicking PTs based on nonspecific imaging features and to monitor for early recurrence of PTs, particularly nonfunctioning PTs lacking specific biochemical markers. This case also illustrated the role of IOUS in identifying multiple PTs missed by visual inspection alone, leading to improved patient outcomes through complete tumor resection.
Association between the aromatase () gene variant rs10046 and cardiovascular risk in postmenopausal women
Dos Santos BR, Casanova G, da Silva TR, Oppermann K and Spritzer PM
To assess the genotypic and allelic distribution of the rs10046 polymorphism in the gene and evaluate whether this aromatase gene variant is associated with cardiovascular risk in postmenopausal women.
The genetics and hormonal basis of human gender identity
Batista RL and Oliveira LMB
Gender identity refers to one's psychological sense of their own gender. Establishing gender identity is a complex phenomenon, and the diversity of gender expression challenges simplistic or unified explanations. For this reason, the extent to which it is determined by nature (biological) or nurture (social) is still debatable. The biological basis of gender identity cannot be modeled in animals and is best studied in people who identify with a gender that is different from the sex of their genitals such as transgender people and people with disorders/differences of sex development. Numerous research studies have delved into unraveling the intricate interplay of hormonal, neuroanatomic/neurofunctional, and genetic factors in the complex development of core gender identity. In this review, we explore and consolidate existing research that provides insights into the biological foundations of gender identity, enhancing our understanding of this intriguing human psychological trait.
Institutional case volumes of thyroidectomies in Brazil and the impact of the COVID-19 pandemic: insights from a national database
Walter LB, Schwengber WK, Scheinpflug AL, Zanella AB, Scheffel RS, Maia AL and Dora JM
Providing widespread access to thyroidectomies while consolidating services in high-volume centers is a significant challenge in healthcare. In this context, from a national perspective, we aimed to analyze the impact of the COVID-19 pandemic on the institutional case volumes of thyroid surgery in Brazil.
Modulating gene expression as a strategy to investigate thyroid cancer biology
de Mello DC, Menezes JM, de Oliveira ATF, Cristovão MM, Kimura ET and Fuziwara CS
Modulating the expression of a coding or noncoding gene is a key tool in scientific research. This strategy has evolved methodologically due to advances in cloning approaches, modeling/algorithms in short hairpin RNA (shRNA) design for knockdown efficiency, and biochemical modifications in RNA synthesis, among other developments. Overall, these modifications have improved the ways to either reduce or induce the expression of a given gene with efficiency and facility for implementation in the lab. Allied with that, the existence of various human cell line models for cancer covering different histotypes and biological behaviors, especially for thyroid cancer, has helped improve the understanding of cancer biology. In this review, we cover the most frequently used current techniques for gene modulation in the thyroid cancer field, such as RNA interference (RNAi), short hairpin RNA (shRNA), and gene editing with CRISPR/Cas9 for inhibiting a target gene, and strategies to overexpress a gene, such as plasmid cloning and CRISPRa. Exploring the possibilities for gene modulation allows the improvement of the scientific quality of the studies and the integration of clinicians and basic scientists, leading to better development of translational research.
Estrogen-mediated modulation of sterile inflammatory markers and baroreflex sensitivity in ovariectomized female Wistar rats
Alam MI, Sami N, Alam A, Wazib S, Dhyani N, Afghan S and Ansari MA
This study aims to explore the role of estrogen in providing cardioprotective benefits to premenopausal women, examining how hormonal differences between sexes influence the prevalence of cardiovascular diseases (CVDs) in women.
Radioiodine treatment in female survivors of pediatric differentiated thyroid carcinoma does not affect future pregnancy rates
Barreto MCA, Treistman N, Cavalcante LBCP, Bulzico D, de Andrade FA, Corbo R, Alves PAG and Vaisman F
Patients with pediatric differentiated thyroid carcinoma (DTC) treated with radioiodine (RAI) therapy may experience long-term side effects, such as gonadal dysfunction. Therefore, it is crucial to understand the impact of this therapy on ovarian reserve and future pregnancy rates.
Basic and translational endocrinology
Nunes MT
The hypothalamus as the central regulator of energy balance and its impact on current and future obesity treatments
Bombassaro B, Araujo EP and Velloso LA
The hypothalamus is a master regulator of energy balance in the body. First-order hypothalamic neurons localized in the arcuate nucleus sense systemic signals that indicate the energy stores in the body. Through distinct projections, arcuate nucleus neurons communicate with second-order neurons, which are mostly localized in the paraventricular nucleus and in the lateral hypothalamus. The signals then proceed to third- and fourth-order neurons that activate complex responses aimed at maintaining whole-body energy homeostasis. During the last 30 years, since the identification of leptin in 1994, there has been a great advance in the unveiling of the hypothalamic and extra-hypothalamic neuronal networks that control energy balance. This has contributed to the characterization of the mechanisms by which glucagon-like peptide-1 receptor agonists promote body mass reduction and has opened new windows of opportunity for the development of drugs to treat obesity. This review presents an overview of the mechanisms involved in the hypothalamic regulation of energy balance and discusses how advancements in this field are contributing to the development of new pharmacological strategies to treat obesity.
Metformin ameliorates peripheral neuropathy in diabetic rats by downregulating autophagy via the AMPK pathway
You F, Xie D, Li C, Yang L and Liu F
Diabetic neuropathy (DN) is an important complication of diabetes mellitus. Autophagy is considered to be potentially involved in the regulation of DN. Metformin is broadly utilized in the first-line treatment of diabetes. The present work aimed to assess whether and how metformin exerts protective effects in DN.
Triiodothyronine (T3) increases the expression of the amphiregulin (AREG) oncogene by activating extranuclear pathways in MCF-7 breast cancer cells
De Sibio MT, Moretto FCF, Olimpio RMC, de Oliveira M, Mathias LS, Peghinelli VV, Tilli HP, Gonçalves BM, Cardoso DBM, Aqua LSD, Depra IC, Lourenço MM, Luvizon AC, Hokama POM, Nunes MT, Sakalem ME and Nogueira CR
Considering that the αvβ3 integrin plays an important role in tumor metastasis, this study investigated the involvement of these pathways in mediating the triiodothyronine (T3) effects on amphiregulin () expression.
Pyriproxyfen, villain or good guy? A brief review
Cabral AP, Maia FPDS, Magliano DC, Graceli JB, Soares P, Morris EAR and Miranda-Alves L
Pyriproxyfen (PPF) acts as a juvenile growth regulator, interfering with normal metamorphosis and blocking the development of insects into adulthood. Although the World Health Organization (WHO) considers the use of PPF at a concentration of 0.01 mg/L as unlikely to pose health risks, recent studies have unveiled potential risks associated with PPF exposure to non-target organisms. Exposure to PPF disrupts insect development primarily by mimicking juvenile hormones; therefore, concerns linger over its impact on unintended species. Studies have highlighted the adverse effects of PPF on aquatic invertebrates, fish, and amphibians and revealed mortality and developmental abnormalities in non-target mosquito species exposed to PPF-treated water. Moreover, PPF may act as an endocrine disruptor, interfering with hormonal pathways crucial for growth, reproduction, and behavior in exposed organisms. Amphibians, for instance, display altered reproductive physiology and developmental abnormalities due to disruptions in endocrine signaling pathways caused by PPF. The ecological ramifications of PPF extend beyond direct toxicity to non-target species. Indirect effects include shifts in food web dynamics and ecosystem functioning. Reductions in insect populations, induced by PPF, can disrupt food availability for higher trophic levels, potentially destabilizing community structure and ecosystem equilibrium. Given mounting evidence of unintended consequences, robust risk assessment and regulatory oversight are imperative. Accurate classification of PPF by regulatory bodies is essential to balancing its role in disease control and pest management benefits with the need to safeguard non-target species and maintain ecosystem health. Future research must prioritize comprehensive assessments of PPF's ecological impact across various habitats and taxa to inform evidence-based policymaking.
Effects of tributyltin on placental and reproductive abnormalities in offspring
da Costa CS, Alahmadi H, Warner GR, Nunes MT, Dias GRM, Miranda-Alves L and Graceli JB
Tributyltin (TBT) is an organotin compound and a common persistent environmental pollutant with endocrine-disrupting chemical (EDC) actions. It can accumulate in the environment at various concentrations throughout the food chain in the ecosystem, posing a risk to human health, especially during critical periods such as gestation and fetal and offspring development. In this review, we report the results of studies describing the consequences of TBT exposure on placental and reproductive parameters in offspring of both sexes. Results from and studies clearly indicate that TBT causes adverse effects on placental development and reproductive parameters in offspring. However, substantial knowledge gaps remain in the literature, requiring further research to better understand the mechanisms behind TBT effects on placental and reproductive disruption in offspring.
Basic, translational, and clinical research - a short reflection
Kopp PA
Pharmacologic Treatment of Obesity in adults and its impact on comorbidities: 2024 Update and Position Statement of Specialists from the Brazilian Association for the Study of Obesity and Metabolic Syndrome (Abeso) and the Brazilian Society of Endocrinology and Metabolism (SBEM)
Moreira RO, Valerio CM, Hohl A, Moulin C, Moura F, Trujilho FR, Gerchman F, Correa LL, Mancini MC, Melo ME, Lamounier RN, van de Sande-Lee S, Trujilho TDG, Miranda PAC and Halpern B
Pharmacological treatment of obesity is passing through many changes in the last decades; different agents have been approved, and newer options are leaning towards higher efficacy and a more favourable safety profile; however, medications approved for a longer time are still available and useful for many patients. This document is an 2024 Update Position Statement of Specialists from the Brazilian Association for the Study of Obesity and Metabolic Syndrome (Abeso) and the Brazilian Society of Endocrinology and Metabolism (SBEM), with the aim of reviewing all the approved medications for the management of obesity in Brazil (sibutramine, orlistat, liraglutide, semaglutide and bupropion/naltrexone fixed dose), with the addition of tirzepatide, that is approved in other countries and likely approved soon in Brazil. The review is focused on efficacy, safety profile and the impact of drugs (based on existing studies) on different comorbidities.
Circulating endothelial progenitor cells and inflammatory markers in type 1 diabetes after an acute session of aerobic exercise
Bock PM, Monteiro RB, Maraschin CK, Alegretti AP, Farias MG, Spagnol F, Lopez PLDC, Santos LP, Helal L, Moraes RS, Umpierre D and Schaan BD
To determine circulating endothelial progenitor cells (EPC) counts and levels of inflammatory markers in individuals with and without type 1 diabetes mellitus (T1DM) in response to an intense aerobic exercise session.
Association between the G/G genotype of the lncRNA rs7158663 polymorphism and proliferative diabetic retinopathy
Brondani LA, Dandolini I, Girardi E, Canani LH, Crispim D and Dieter C
To investigate the association between the long noncoding RNAs (lncRNAs) () rs7158663 polymorphism and diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM).
Increased NOX-dependent ROS production and proportionally enhanced antioxidant response in white adipose tissue of male rats
Nascimento JF, de Oliveira KA, de Freitas PA, Falci JAM, Vasconcelos RP, Magalhães SC, Farias TM, Alonso-Vale MIC, Loureiro ACC, de Carvalho DP, Fortunato RS and de Oliveira AC
This study aimed to investigate the redox balance in subcutaneous and retroperitoneal fat pads of male and female Wistar rats.
Early expression of neuroinflammation in an untreated fatal case of diabetic ketoacidosis
Artlett CM, Abdelwahab SH, Hoffman WH and Calikoglu AS
We present the case of a young adult who had lethargy and significant weight loss for the three weeks before his death. The history of the present illness suggested a prodrome of several weeks, with progressive weakness indicating an advancing metabolic decompensation. To our knowledge, this is the first study performed on human brain tissue with type 1 diabetes (T1D) and likely diabetic ketoacidosis (DKA) before treatment. We studied neuroinflammatory markers in an insulin-deficient state without treatment compared with those found in a treated patient with T1D/DKA of similar age and race who died shortly after treatment. The frontal cortex and hippocampus were stained for tight junction proteins, RAGE, NLRP3, and HMGB1. Other markers that can disrupt the blood-brain barrier, such as IL-17, IL-6, IL-1β, GFAP, and IL-10 were also tested. This case study reveals that neuroinflammatory markers are expressed in the DKA brain at a lower level before treatment than those found to be expressed in the brain after treatment. These findings suggest that in DKA, dehydration minimizes inflammation which could be exacerbated with fluids promoting neuroinflammation and cognitive deficits. These findings require further studies and could identify therapeutic targets to reduce the progression of neuroinflammation and brain edema.
Fertility induction associated with improved peripheral reproductive parameters in male mice subjected to GH and levothyroxine replacement
Azevedo BV, Marques JM, Trigueiro N, Yariwake VY, Veras MM, Tamashiro LK, Cruz R and de Carvalho LRS
The aim of this study was to characterize the parameters of reproductive anatomy and pituitary hormone expression levels in ames dwarf mice ).