Abstract:
:This review focuses on the biologic importance of the vitamin D binding protein (DBP) with emphasis on its regulation of total and free vitamin D metabolite levels in various clinical conditions. Nearly all DBP is produced in the liver, where its regulation is influenced by estrogen, glucocorticoids and inflammatory cytokines but not by vitamin D itself. DBP is the most polymorphic protein known, and different DBP alleles can have substantial impact on its biologic functions. The three most common alleles-Gc1f, Gc1s, Gc2-differ in their affinity with the vitamin D metabolites and have been variably associated with a number of clinical conditions. Although DBP has a number of biologic functions independent of vitamin D, its major biologic function is that of regulating circulating free and total levels of vitamin D metabolites. 25 hydroxyvitamin D (25(OH)D) is the best studied form of vitamin D as it provides the best measure of vitamin D status. In a normal non-pregnant individual, approximately 0.03% of 25(OH)D is free; 85% is bound to DBP, 15% is bound to albumin. The free hormone hypothesis postulates that only free 25(OH)D can enter cells. This hypothesis is supported by the observation that mice lacking DBP, and therefore with essentially undetectable 25(OH)D levels, do not show signs of vitamin D deficiency unless put on a vitamin D deficient diet. Similar observations have recently been described in a family with a DBP mutation. This hypothesis also applies to other protein bound lipophilic hormones including glucocorticoids, sex steroids, and thyroid hormone. However, tissues expressing the megalin/cubilin complex, such as the kidney, have the capability of taking up 25(OH)D still bound to DBP, but most tissues rely on the free level. Attempts to calculate the free level using affinity constants generated in a normal individual along with measurement of DBP and total 25(OH)D have not accurately reflected directly measured free levels in a number of clinical conditions. In this review, we examine the impact of different clinical conditions as well as different DBP alleles on the relationship between total and free 25(OH)D, using only data in which the free 25(OH)D level was directly measured. The major conclusion is that a number of clinical conditions alter this relationship, raising the question whether measuring just total 25(OH)D might be misleading regarding the assessment of vitamin D status, and such assessment might be improved by measuring free 25(OH)D instead of or in addition to total 25(OH)D.
journal_name
Front Endocrinol (Lausanne)journal_title
Frontiers in endocrinologyauthors
Bikle DD,Schwartz Jdoi
10.3389/fendo.2019.00317subject
Has Abstractpub_date
2019-05-28 00:00:00pages
317issn
1664-2392journal_volume
10pub_type
杂志文章,评审abstract:BACKGROUND:Non-alcoholic fatty liver disease (NAFLD) is one of the most common forms of chronic liver diseases closely associated with obesity and insulin resistance; deficient growth hormone (GH) action in liver has been implicated as a mechanism. Here, we investigated the evolution of NAFLD in aged mice with liver-sp...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2014.00218
更新日期:2014-12-18 00:00:00
abstract::Obesity has emerged as one of the most burdensome conditions in modern society. In this context, understanding the mechanisms controlling food intake is critical. At present, the adipocyte-derived hormone leptin and the pancreatic β-cell-derived hormone insulin are considered the principal anorexigenic hormones. Altho...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章,评审
doi:10.3389/fendo.2016.00138
更新日期:2016-10-20 00:00:00
abstract::It has been generally assumed that insulin circulates freely in blood. However it can also interact with plasma proteins. Insulin receptors are located in the membrane of target cells and consist of an alpha and beta subunits with a tyrosine kinase cytoplasmic domain. The ectodomain, called soluble insulin receptor (S...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2014.00095
更新日期:2014-06-19 00:00:00
abstract::Exercise training triggers numerous positive adaptations through the regulation of genes controlling muscle structure and function. Epigenetic modifications, including DNA methylation, participate in transcriptional activation by allowing the recruitment of the transcription machinery to gene promoters. Exercise induc...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2016.00165
更新日期:2016-12-23 00:00:00
abstract::Biological steroids were traditionally thought to be synthesized exclusively by the adrenal glands and gonads. Recent decades have seen the discovery of neurosteroid production that acts locally within the central nervous system to affect physiology and behavior. These actions include, for example, regulation of aggre...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2018.00270
更新日期:2018-06-18 00:00:00
abstract::Background: Obesity and maternal age are the two most important factors independently affecting the risk of gestational diabetes mellitus (GDM). However, the age differences in the association between obesity and GDM remain unclear. The objectives of this cohort study included: (1) to determine the current incidence o...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2020.00636
更新日期:2020-09-11 00:00:00
abstract::The G Protein-Coupled Estrogen Receptor (GPER) is a novel membrane-bound receptor that mediates non-genomic actions of the primary female sex hormone 17β-estradiol. Studies over the past two decades have elucidated the beneficial actions of this receptor in a number of cardiometabolic diseases. This review will focus ...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章,评审
doi:10.3389/fendo.2019.00919
更新日期:2020-01-14 00:00:00
abstract::The estrogen receptor and glucocorticoid receptor are members of the nuclear receptor superfamily that can signal using both non-genomic and genomic transcriptional modes. Though genomic modes of signaling have been well characterized and several behaviors attributed to this signaling mechanism, the physiological sign...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章,评审
doi:10.3389/fendo.2015.00018
更新日期:2015-02-16 00:00:00
abstract::Accumulating evidence shows that H2S has physiological functions in various tissues and organs. It includes regulation of neuronal activity, vascular tension, a release of insulin, and protection of the heart, kidney, and brain from ischemic insult. H2S is produced by enzymes from l-cysteine; cystathionine β-synthase,...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2013.00087
更新日期:2013-07-16 00:00:00
abstract::Older women with type 2 diabetes mellitus (DM) have higher bone mineral density (BMD) but also have higher rates of fracture compared to those without DM. Limited evidence suggests that DM may also be associated with more rapid bone loss. To determine if bone loss rates differ by DM status in older women, we analyzed ...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2013.00062
更新日期:2013-05-30 00:00:00
abstract::The rapid increase of obesity rates worldwide is associated with chronic liver injury due to non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. Chronic liver inflammation drives hepatic fibrosis, which is a highly conserved and coordinated protective response to tissue injury, and is a reversible pro...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章,评审
doi:10.3389/fendo.2018.00455
更新日期:2018-08-21 00:00:00
abstract::Maternal over-nutrition can lead to metabolic disorders in offspring, whereas maternal dietary genistein may have beneficial effects on the metabolic health of offspring. Our objective was to determine whether maternal dietary genistein could attenuate the detrimental effects of a maternal high-fat diet on their offsp...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2018.00516
更新日期:2018-09-04 00:00:00
abstract::Aim: Type 2 Diabetes Mellitus (T2DM) is associated with both microvascular complications such as diabetic retinopathy (DR), and macrovascular complications like coronary artery disease (CAD). Genetic risk factors have a role in the development of these complications. In the present case-control study, we investigated ...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2019.00283
更新日期:2019-05-03 00:00:00
abstract::Linagliptin, one of the five dipeptidyl peptidase-4 inhibitors available, has recently entered the market both in the US and in most European countries for treatment of type 2 diabetes mellitus. It presents a xanthine-based structure, and is characterized by unique pharmacokinetics, with non-linear profile, long termi...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2013.00016
更新日期:2013-02-26 00:00:00
abstract::Background: Disturbance of immunometabolic signaling is a key process involved in the progression of obesity. Microglia-the resident immune cells in the brain, initiate local immune responses. It is known that hypercaloric diets lead to microglial activation. Previously, we observed that hypothalamic microglial cells ...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2019.00424
更新日期:2019-06-26 00:00:00
abstract::Introduction: Although pre-treatment with a GnRH agonist can reduce the size of adenomyosis lesions, the supra-physiological hormone level induced by controlled ovarian hyperstimulation (COH) may negate the usefulness of the GnRH agonist in patients with adenomyosis lesions, leading to continued poor outcomes in fresh...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2020.00318
更新日期:2020-05-29 00:00:00
abstract::RFamide-related peptide-3 (RFRP-3) [mammalian ortholog to gonadotropin-inhibiting hormone (GnIH)] potently inhibits gonadotropin secretion in mammals. Studies of RFRP-3 immunoreactivity and Rfrp expression (the gene encoding RFRP-3) in mammalian brains have uncovered several possible pathways regulating RFRP-3 neurons...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章,评审
doi:10.3389/fendo.2015.00150
更新日期:2015-09-24 00:00:00
abstract::The orexigenic peptide hormone ghrelin is synthesized in the stomach and its receptor growth hormone secretagogue receptor (GHSR1a) is expressed mainly in the central nervous system (CNS). In this review, we confine our discussion to the physiological role of GHSR1a in the brain. Paradoxically, despite broad expressio...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章,评审
doi:10.3389/fendo.2014.00129
更新日期:2014-08-18 00:00:00
abstract::The estimated number of testicular olfactory receptors (ORs) in mammals range between 20 and 66. Previous data reported the role of hOR17-4 and mOR23 in sperm-oocyte chemiotaxis. Proteomic analysis was performed to understand which are the ORs expressed in seminal plasma. Seminal samples by four fertile men were analy...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2017.00379
更新日期:2018-01-23 00:00:00
abstract::[This corrects the article DOI: 10.3389/fendo.2019.00668.]. ...
journal_title:Frontiers in endocrinology
pub_type: 已发布勘误
doi:10.3389/fendo.2019.00904
更新日期:2020-01-22 00:00:00
abstract::Osteoporosis is metabolic bone disease caused by an altered balance between bone anabolism and catabolism. This dysregulated balance is responsible for fragile bones that fracture easily after minor falls. With an aging population, the incidence is rising and as yet pharmaceutical options to restore this imbalance is ...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章,评审
doi:10.3389/fendo.2019.00006
更新日期:2019-01-29 00:00:00
abstract:Background:For detecting tumor recurrence of medullary thyroid carcinoma (MTC) in the neck, an appropriate frequency and interval of postoperative ultrasonography (US) surveillance remains unclear. This study aimed to assess an appropriate interval and frequency of postoperative neck US surveillance for detecting tumor...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2018.00102
更新日期:2018-03-15 00:00:00
abstract::At least 57 independent loci within the human genome confer varying degrees of risk for the development of type 1 diabetes (T1D). The majority of these variants are thought to contribute to overall genetic risk by modulating host innate and adaptive immune responses, ultimately resulting in a loss of immunological tol...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章,评审
doi:10.3389/fendo.2017.00276
更新日期:2017-10-18 00:00:00
abstract::Immobilization results in a substantial bone loss and increased fracture risk. Powerful bone anabolic therapies are necessary to counteract the bone loss and reduce fracture risk during periods with immobilization. Intermittent parathyroid hormone 1-34 (PTH) (teriparatide) and PTH related peptide analog abaloparatide ...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2020.588773
更新日期:2020-10-09 00:00:00
abstract::O-linked N-acetylglucosaminylation (O-GlcNAcylation) is a reversible post-translational modification consisting in the addition of a sugar moiety to serine/threonine residues of cytosolic or nuclear proteins. Catalyzed by O-GlcNAc-transferase (OGT) and removed by O-GlcNAcase, this dynamic modification is dependent on ...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2013.00099
更新日期:2013-08-12 00:00:00
abstract::Intrauterine growth restriction (IUGR) is a complex global healthcare issue. Concerted research and clinical efforts have improved our knowledge of the neurodevelopmental sequelae of IUGR which has raised the profile of this complex problem. Nevertheless, there is still a lack of therapies to prevent the substantial r...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章,评审
doi:10.3389/fendo.2019.00188
更新日期:2019-03-29 00:00:00
abstract::The plasticity of the individual epigenetic landscape that goes to countless rearrangements throughout life is closely the reflection of environmental factors such as chemical exposure, socio-economic status and nutrient intakes both early and late in life. The Mini Nutritional Assessment (MNA) is a well-validated too...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2019.00672
更新日期:2019-10-01 00:00:00
abstract::The present study aimed to compare effects of increasing chronic stress load on the stress response of European seabass (Dicentrarchus labrax) and gilthead seabream (Sparus aurata) to identify neuroendocrine functions that regulate this response. Fish were left undisturbed (controls) or exposed to three levels of chro...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2018.00451
更新日期:2018-08-13 00:00:00
abstract::Obesity is associated with inflammation and type 2 diabetes. Innate immune system comprised of cellular and molecular components plays an important role in the inflammatory reactions. Immune cells like macrophages and their cell surface pattern-recognition receptors (PRRs) are representative for innate immunity promot...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2013.00105
更新日期:2013-08-21 00:00:00
abstract::GPER-1 is a novel membrane sited G protein-coupled estrogen receptor. Clinical studies have shown that patients suffering an estrogen receptor α (ERα)/GPER-1 positive, breast cancer have a lower survival rate than those who have developed ERα-positive/GPER-1 negative tumors. Moreover, absence of GPER-1 improves the pr...
journal_title:Frontiers in endocrinology
pub_type: 杂志文章
doi:10.3389/fendo.2020.563165
更新日期:2020-09-30 00:00:00