Follicle-Stimulating Hormone Sweetness: How Carbohydrate Structures Impact on the Biological Function of the Hormone.

Follicle-stimulating hormone (FSH), or follitropin, exists in multiple molecular forms due largely to its protein-carbohydrate composition and the complexity of the glycans attached to the protein core. The heterogeneity of gonadotropins exists in two forms, macroheterogeneity, which results from the absence of one or two oligosaccharide chains in the ß-subunit, and microheterogeneity which results from variation in the structures and complexity of the glycans attached to the hormone. In the clinical arena, FSH compounds are widely used by fertility specialists to promote ovarian follicle growth and maturation to a preovulatory follicle containing a fertilization-competent oocyte.

Differential effects of follicle-stimulating hormone glycoforms on the transcriptome profile of cultured rat granulosa cells as disclosed by RNA-seq.

It has been documented that variations in glycosylation on glycoprotein hormones, confer distinctly different biological features to the corresponding glycoforms when multiple in vitro biochemical readings are analyzed. We here applied next generation RNA sequencing to explore changes in the transcriptome of rat granulosa cells exposed for 0, 6, and 12 h to 100 ng/ml of four highly purified follicle-stimulating hormone (FSH) glycoforms, each exhibiting different glycosylation patterns: a. human pituitary FSH18/21 (hypo-glycosylated); b.

Tracking conformational transitions of the gonadotropin hormone receptors in a bilayer of (SDPC) poly-unsaturated lipids from all-atom molecular dynamics simulations.

Glycoprotein hormone receptors [thyrotropin (TSHR), luteinizing hormone/chorionic gonadotropin (LHCGR), and follicle stimulating hormone (FSHR) receptors] are rhodopsin-like G protein-coupled receptors. These receptors display common structural features including a prominent extracellular domain with leucine-rich repeats (LRR) stabilized by β-sheets and a long and flexible loop known as the hinge region (HR), and a transmembrane (TM) domain with seven α-helices interconnected by intra- and extracellular loops. Binding of the ligand to the LRR resembles a hand coupling transversally to the α- and β-subunits of the hormone, with the thumb being the HR.

Estrogen regulated transcription of the non-estrogen-regulated hamster uteroglobin gene in MCF-7 cells.

To study the estrogen regulated transcription of the uteroglobin (UG) gene, the founding member of the secretoglobin family widely expressed in many different mammalian species, we re-created functional estrogen response elements (EREs) in the UG gene promoter from a species where UG expression is not regulated by estrogens: the hamster Mesocricetus auratus (Ma), to ascertain if the lack of functional EREs is the real cause of its estrogen insensitivity. Functional EREs in the hamster promoter, including the consensus ERE (cERE), failed to respond to an appropriate estrogen stimulus compared with its estrogen regulated ortholog from the brown hare Lepus capensis (Lc). As the nucleotide sequence is the only difference between genetic constructs from these two species, we suspected that the UG promoter from the hamster probably contains cis-acting genetic elements that negatively impairs the estrogen-regulated transcription mediated by the functional ERE.

Differential effects of follicle-stimulating hormone glycoforms on the transcriptome profile of cultured rat granulosa cells as disclosed by RNA-seq.

It has been documented that variations in glycosylation on glycoprotein hormones, confer distinctly different biological features to the corresponding glycoforms when multiple biochemical readings are analyzed. We here applied next generation RNA sequencing to explore changes in the transcriptome of rat granulosa cells exposed for 0, 6, and 12 h to 100 ng/ml of four highly purified follicle-stimulating hormone (FSH) glycoforms, each exhibiting different glycosylation patterns: human pituitary FSH and equine FSH (FSH) (hypo-glycosylated), and human FSH and chinese-hamster ovary cell-derived human recombinant FSH (FSH) (fully-glycosylated). Total RNA from triplicate incubations was prepared from FSH glycoform-exposed cultured granulosa cells obtained from DES-pretreated immature female rats, and RNA libraries were sequenced in a HighSeq 2500 sequencer (2 × 125 bp paired-end format, 10-15 × 10 reads/sample).

Follicle-Stimulating Hormone Biological Products: Does Potency Predict Clinical Efficacy?

Follicle-stimulating hormone (FSH), together with luteinizing hormone (LH) and human chorionic gonadotropin (hCG), plays a fundamental role in human reproduction. The discovery of FSH and other gonadotropins was a defining moment in our understanding of reproduction and led to the development of many treatments for infertility. In this regard, exogenous FSH has been used to treat infertility in women for decades.

Pods or a Polyphenolic Extract Derived from Them Exert Immunomodulatory, Metabolic, Renoprotective, and Prebiotic Effects in Mice Fed a High-Fat Diet.

Obesity causes systemic inflammation, hepatic and renal damage, as well as gut microbiota dysbiosis. Alternative vegetable sources rich in polyphenols are known to prevent or delay the progression of metabolic abnormalities during obesity. (VF) is a potent source of polyphenols with antioxidant and anti-inflammatory activities with potential anti-obesity effects.

Metabolomics analysis identifies glutamic acid and cystine imbalances in COVID-19 patients without comorbid conditions. Implications on redox homeostasis and COVID-19 pathophysiology.

It is well known that the presence of comorbidities and age-related health issues may hide biochemical and metabolic features triggered by SARS-CoV-2 infection and other diseases associated to hypoxia, as they are by themselves chronic inflammatory conditions that may potentially disturb metabolic homeostasis and thereby negatively impact on COVID-19 progression. To unveil the metabolic abnormalities inherent to hypoxemia caused by COVID-19, we here applied gas chromatography coupled to mass spectrometry to analyze the main metabolic changes exhibited by a population of male patients less than 50 years of age with mild/moderate and severe COVID-19 without pre-existing comorbidities known to predispose to life-threatening complications from this infection. Several differences in serum levels of particular metabolites between normal controls and patients with COVID-19 as well as between mild/moderate and severe COVID-19 were identified.

Targeting trafficking as a therapeutic avenue for misfolded GPCRs leading to endocrine diseases.

G protein-coupled receptors (GPCRs) are plasma membrane proteins associated with an array of functions. Mutations in these receptors lead to a number of genetic diseases, including diseases involving the endocrine system. A particular subset of loss-of-function mutant GPCRs are misfolded receptors unable to traffic to their site of function ( the cell surface plasma membrane).

Comparative Assessment of the Structural Features of Originator Recombinant Human Follitropin Alfa Versus Recombinant Human Follitropin Alfa Biosimilar Preparations Approved in Non-European Regions.

Although the full primary structures of the alfa and beta subunits of reference r-hFSH-alfa and its biosimilars are identical, cell context-dependent differences in the expressing cell lines and manufacturing process can lead to variations in glycosylation profiles. In the present study, we compared the structural features of reference r-hFSH-alfa with those of five biosimilar preparations approved in different global regions outside Europe (Primapur, Jin Sai Heng, Follitrope, Folisurge, and Corneumon) with respect to glycosylation, macro- and microheterogeneity, and other post-translational modifications and higher order structure. The mean proportion of -glycosylation-site occupancy was highest in reference r-hFSH-alfa, decreasing sequentially in Primapur, Jin Sai Heng, Corneumon, Follisurge and Follitrope, respectively.

Genistein Stimulation of White Adipose Tissue Thermogenesis Is Partially Dependent on GPR30 in Mice.

Scope: Genistein increases whole body energy expenditure by stimulating white adipose tissue (WAT) browning and thermogenesis. G-Coupled receptor GPR30 can mediate some actions of genistein, however, it is not known whether it is involved in the activation of WAT-thermogenesis. Thus, the aim of the study is to determine whether genistein activates thermogenesis coupled to an increase in WAT browning and mitochondrial activity, in GPR30 and GPR30 mice.

A Brief Journey through Protein Misfolding in Transthyretin Amyloidosis (ATTR Amyloidosis).

Transthyretin (TTR) amyloidogenesis involves the formation, aggregation, and deposition of amyloid fibrils from tetrameric TTR in different organs and tissues. While the result of amyloidoses is the accumulation of amyloid fibrils resulting in end-organ damage, the nature, and sequence of the molecular causes leading to amyloidosis may differ between the different variants. In addition, fibril accumulation and toxicity vary between different mutations.

Misfolded G Protein-Coupled Receptors and Endocrine Disease. Molecular Mechanisms and Therapeutic Prospects.

Misfolding of G protein-coupled receptors (GPCRs) caused by mutations frequently leads to disease due to intracellular trapping of the conformationally abnormal receptor. Several endocrine diseases due to inactivating mutations in GPCRs have been described, including X-linked nephrogenic diabetes insipidus, thyroid disorders, familial hypocalciuric hypercalcemia, obesity, familial glucocorticoid deficiency [melanocortin-2 receptor, MC2R (also known as adrenocorticotropin receptor, ACTHR), and reproductive disorders. In these mutant receptors, misfolding leads to endoplasmic reticulum retention, increased intracellular degradation, and deficient trafficking of the abnormal receptor to the cell surface plasma membrane, causing inability of the receptor to interact with agonists and trigger intracellular signaling.

REVISTA DE INVESTIGACIóN CLíNICA -CLINICAL AND TRANSLATIONAL INVESTIGATION-: EDITORS' CHOICES 6 YEARS LATER.

In this article, a series of original manuscripts and reviews published between 2015 and 2021 in the Revista de Investigación Clínica -Clinical and Translational Investigation- chosen by the Editors are presented. The articles were selected according to what the editors considered are the most outstanding contributions based on originality, and the potential impact of the information provided on translational medicine, rather than on the number of readings and citations.

THE EVOLVING HISTORY OF THE REVISTA DE INVESTIGACIóN CLíNICA.

The Revista de Investigación Clínica (RIC) was established in 1948. It has been published continuously for 73 years. Until 2009, it was the journal of the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (formerly Hospital de Enfermedades de la Nutrición, and later named Instituto Nacional de la Nutrición), and thereafter it became the official journal of the Mexican National Institutes of Health.

New Human Follitropin Preparations: How Glycan Structural Differences May Affect Biochemical and Biological Function and Clinical Effect.

It is well accepted that pituitary follitropin is secreted into the circulation as a mixture of variants, which differ not in primary structure but rather at the level of glycosylation. These glycosidic forms vary in the number of glycosylation sites filled, complexity of glycosidic chains, and sialylation and sulfation. It is generally agreed that high sialylation, 2,3 sialic acid capping of terminal N-acetyl galactosamine or galactose leads to longer circulating half-life, by blocking binding of asialoglycoprotein receptor (ASGPR) in the liver.

Mood variations and personality traits in patients with epilepsy over the course of their menstrual cycle.

Introduction: The incidence of mood disorders and psychopathology is more frequent in patients with epilepsy (PWE) than in the general population. Also, it has been reported that PWE suffer more seizures during certain phases of their menstrual cycle (MC). Still, limited information exists regarding the relationship between the physical and emotional changes during the MC in PWE.

Scientific medical journals in Mexico.

This symposium describes the main characteristics of six Mexican scientific journals indexed in Journal Citation Reports: Archives of Medical Research, Revista de Investigación Clínica-Clinical and Translational Investigation, Gaceta Médica de México, Salud Pública de México, Cirugía y Cirujanos and Salud Mental. Particular emphasis is given to their historical and organizational aspects, as well as to their main achievements recognized by the national and international scientific community. En este simposio se describen las principales características de seis revistas científicas mexicanas reconocidas por el.

Metformin reverses mesenchymal phenotype of primary breast cancer cells through STAT3/NF-κB pathways.

Background: Breast cancer currently is the most frequently diagnosed neoplasm and the leading cause of death from cancer in women worldwide, which is mainly due to metastatic disease. Increasing our understanding of the molecular mechanisms leading to metastasis might thus improve the pharmacological management of the disease. Epithelial-mesenchymal transition (EMT) is a key factor that plays a major role in tumor metastasis.

Modulation of proteostasis and protein trafficking: a therapeutic avenue for misfolded G protein-coupled receptors causing disease in humans.

Proteostasis refers to the process whereby the cell maintains in equilibrium the protein content of different compartments. This system consists of a highly interconnected network intended to efficiently regulate the synthesis, folding, trafficking, and degradation of newly synthesized proteins. Molecular chaperones are key players of the proteostasis network.