Abstract:
:Phosphate plays essential roles in many biological processes, and the serum phosphate level is tightly controlled. Chronic hypophosphatemia causes impaired mineralization of the bone matrix and results in rickets and osteomalacia. Fibroblast growth factor 23 (FGF23) is a bone-derived hormone that regulates phosphate metabolism. FGF23 excess induces hypophosphatemia via impaired phosphate reabsorption in the renal proximal tubules and decreased phosphate absorption in the intestines. There are several types of genetic and acquired FGF23-related hypophosphatemic diseases. Among these diseases, X-linked hypophosphatemia (XLH), which is caused by inactivating mutations in the phosphate-regulating endopeptidase homolog, X-linked (PHEX) gene, is the most prevalent form of genetic FGF23-related hypophosphatemic rickets. Another clinically relevant form of FGF23-related hypophosphatemic disease is tumor-induced osteomalacia (TIO), a paraneoplastic syndrome associated with FGF23-producing tumors. A combination of active vitamin D and phosphate salts is the current medical therapy used to treat patients with XLH and inoperative TIO. However, this therapy has certain efficacy- and safety-associated limitations. Several measures to inhibit FGF23 activity have been considered as possible new treatments for FGF23-related hypophosphatemic diseases. In particular, a humanized monoclonal antibody for FGF23 (burosumab) is a promising treatment in patients with XLH and TIO. This review will focus on the phosphate metabolism and the pathogenesis and treatment of FGF23-related hypophosphatemic diseases.
journal_name
Endocr Revjournal_title
Endocrine reviewsauthors
Kinoshita Y,Fukumoto Sdoi
10.1210/er.2017-00220subject
Has Abstractpub_date
2018-06-01 00:00:00pages
274-291issue
3eissn
0163-769Xissn
1945-7189pii
4825438journal_volume
39pub_type
杂志文章,评审abstract::Substantial advances have been made recently in the pathobiology of pituitary tumors. Similar to many other endocrine tumors, over the last few years we have recognized the role of germline and somatic mutations in a number of syndromic or nonsyndromic conditions with pituitary tumor predisposition. These include the ...
journal_title:Endocrine reviews
pub_type: 杂志文章
doi:10.1210/endrev/bnaa006
更新日期:2020-12-01 00:00:00
abstract::Iodine deficiency has multiple adverse effects in humans, termed iodine deficiency disorders, due to inadequate thyroid hormone production. Globally, it is estimated that 2 billion individuals have an insufficient iodine intake, and South Asia and sub-Saharan Africa are particularly affected. However, about 50% of Eur...
journal_title:Endocrine reviews
pub_type: 杂志文章,评审
doi:10.1210/er.2009-0011
更新日期:2009-06-01 00:00:00
abstract::The integrity of the Tg structure as a protein is essential for adequate synthesis of thyroid hormone. Also a large supply of iodine and of thyroid hormone is stored into the Tg molecule and available for secretion on demand. Mutations in Tg gene or hyposialylated Tg due to a defective sialyltransferase activity would...
journal_title:Endocrine reviews
pub_type: 杂志文章,评审
doi:10.1210/edrv-14-2-165
更新日期:1993-04-01 00:00:00
abstract::There is a large body of literature showing that prolactin (PRL) exerts growth-promoting activities in breast cancer, and possibly in prostate cancer and prostate hyperplasia. In addition, increasing evidence argues for the involvement of locally produced (autocrine) PRL, perhaps even more than pituitary-secreted (end...
journal_title:Endocrine reviews
pub_type: 杂志文章,评审
doi:10.1210/er.2004-0016
更新日期:2005-05-01 00:00:00
abstract::Rapid effects of steroid hormones result from the actions of specific receptors localized most often to the plasma membrane. Fast-acting membrane-initiated steroid signaling (MISS) leads to the modification of existing proteins and cell behaviors. Rapid steroid-triggered signaling through calcium, amine release, and k...
journal_title:Endocrine reviews
pub_type: 杂志文章,评审
doi:10.1210/er.2007-0022
更新日期:2007-12-01 00:00:00
abstract::Cells from the chorionic girdle of the equine trophoblast invade the maternal endometrium at day 36 of gestation and become established as secretory elements known as the endometrial cups. These structures, which persist for 40-60 days, produce a gonadotropin which can be found in circulation until about day 130 of ge...
journal_title:Endocrine reviews
pub_type: 杂志文章,评审
doi:10.1210/edrv-12-1-27
更新日期:1991-02-01 00:00:00
abstract::Normal reproductive function in mammals requires precise control of LH synthesis and secretion by gonadotropes of the anterior pituitary. Synthesis of LH requires expression of two genes [alpha-glycoprotein subunit (alphaGSU) and LHbeta] located on different chromosomes. Hormones from the hypothalamus and gonads modul...
journal_title:Endocrine reviews
pub_type: 杂志文章,评审
doi:10.1210/er.2003-0029
更新日期:2004-08-01 00:00:00
abstract::This review presents a comprehensive discussion of the clinical condition of delayed puberty, a common presentation to the pediatric endocrinologist, which may present both diagnostic and prognostic challenges. Our understanding of the genetic control of pubertal timing has advanced thanks to active investigation in t...
journal_title:Endocrine reviews
pub_type: 杂志文章,评审
doi:10.1210/er.2018-00248
更新日期:2019-10-01 00:00:00
abstract::Polycystic ovary syndrome (PCOS) was hypothesized to result from functional ovarian hyperandrogenism (FOH) due to dysregulation of androgen secretion in 1989-1995. Subsequent studies have supported and amplified this hypothesis. When defined as otherwise unexplained hyperandrogenic oligoanovulation, two-thirds of PCOS...
journal_title:Endocrine reviews
pub_type: 杂志文章,评审
doi:10.1210/er.2015-1104
更新日期:2016-10-01 00:00:00
abstract::Access to effective affordable contraception is critical for individual and public health. A wide range of hormonal contraceptives (HCs), which differ in composition, concentration of the progestin component, frequency of dosage, and method of administration, is currently available globally. However, the options are r...
journal_title:Endocrine reviews
pub_type: 杂志文章,评审
doi:10.1210/er.2017-00103
更新日期:2018-02-01 00:00:00
abstract::In humans and other mammalian species, the pool of resting primordial follicles serves as the source of developing follicles and fertilizable ova for the entire length of female reproductive life. One question that has intrigued biologists is: what are the mechanisms controlling the activation of dormant primordial fo...
journal_title:Endocrine reviews
pub_type: 杂志文章,评审
doi:10.1210/er.2008-0048
更新日期:2009-08-01 00:00:00
abstract::Members of the TGF-beta superfamily, which includes TGF-betas, growth differentiation factors, bone morphogenetic proteins, activins, inhibins, and glial cell line-derived neurotrophic factor, are synthesized as prepropeptide precursors and then processed and secreted as homodimers or heterodimers. Most ligands of the...
journal_title:Endocrine reviews
pub_type: 杂志文章,评审
doi:10.1210/er.2002-0003
更新日期:2002-12-01 00:00:00
abstract::Immune checkpoints are small molecules expressed by immune cells that play critical roles in maintaining immune homeostasis. Targeting the immune checkpoints cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed death 1 (PD-1) with inhibitory antibodies has demonstrated effective and durable antitumor ac...
journal_title:Endocrine reviews
pub_type: 杂志文章,评审
doi:10.1210/er.2018-00006
更新日期:2019-02-01 00:00:00
abstract::It is well known that GH is important in the regulation of longitudinal bone growth. Its role in the regulation of bone metabolism in man has not been understood until recently. Several in vivo and in vitro studies have demonstrated that GH is important in the regulation of both bone formation and bone resorption. In ...
journal_title:Endocrine reviews
pub_type: 杂志文章,评审
doi:10.1210/edrv.19.1.0324
更新日期:1998-02-01 00:00:00
abstract::Recent identification of new selenocysteine-containing proteins has revealed relationships between the two trace elements selenium (Se) and iodine and the hormone network. Several selenoproteins participate in the protection of thyrocytes from damage by H(2)O(2) produced for thyroid hormone biosynthesis. Iodothyronine...
journal_title:Endocrine reviews
pub_type: 杂志文章,评审
doi:10.1210/er.2001-0034
更新日期:2005-12-01 00:00:00
abstract::Investigations of biological programs that are controlled by gene transcription have mainly studied the regulation of transcription factors. However, there are examples in which the primary focus of biological regulation is at the level of a transcriptional coactivator. We have reviewed here the molecular mechanisms a...
journal_title:Endocrine reviews
pub_type: 杂志文章,评审
doi:10.1210/er.2002-0012
更新日期:2003-02-01 00:00:00
abstract::Many hormones, growth factors, and cytokines regulate proliferation of their target cells. Perhaps the most universal signaling cascades required for proliferative responses are those initiated by transient rises in intracellular calcium (Ca(2+)). The major intracellular receptor for Ca(2+) is calmodulin (CaM). CaM is...
journal_title:Endocrine reviews
pub_type: 杂志文章,评审
doi:10.1210/er.2003-0008
更新日期:2003-12-01 00:00:00
abstract::There has been an alarming increase in the prevalence of obesity in people with type 1 diabetes in recent years. Although obesity has long been recognized as a major risk factor for the development of type 2 diabetes and a catalyst for complications, much less is known about the role of obesity in the initiation and p...
journal_title:Endocrine reviews
pub_type: 杂志文章,评审
doi:10.1210/er.2017-00191
更新日期:2018-10-01 00:00:00
abstract::Thyroid-associated ophthalmopathy (TAO) is a complex disease process presumed to emerge from autoimmunity occurring in the thyroid gland, most frequently in Graves disease (GD). It is disfiguring and potentially blinding, culminating in orbital tissue remodeling and disruption of function of structures adjacent to the...
journal_title:Endocrine reviews
pub_type: 杂志文章,评审
doi:10.1210/er.2018-00066
更新日期:2019-02-01 00:00:00
abstract::People with type 2 diabetes are disproportionately affected by cardiovascular disease (CVD), compared with those without diabetes. Traditional risk factors do not fully explain this excess risk, and other "nontraditional" risk factors may be important. This review will highlight the importance of nontraditional risk f...
journal_title:Endocrine reviews
pub_type: 杂志文章,评审
doi:10.1210/er.2002-0034
更新日期:2004-02-01 00:00:00
abstract::Ovarian steroids normally exert homeostatic negative feedback on GnRH release. During sustained exposure to elevated estradiol in the late follicular phase of the reproductive cycle, however, the feedback action of estradiol switches to positive, inducing a surge of GnRH release from the brain, which signals the pitui...
journal_title:Endocrine reviews
pub_type: 杂志文章,评审
doi:10.1210/er.2009-0023
更新日期:2010-08-01 00:00:00
abstract::Hormones and cytokines regulate many cellular functions by activating the ubiquitous cAMP-dependent protein kinase (A kinase) system. Newly synthesized cAMP molecules bind to regulatory (R) subunits in A kinase holoenzymes, causing them to release their catalytic (C) subunits. These free C subunits then phosphorylate ...
journal_title:Endocrine reviews
pub_type: 杂志文章,评审
doi:10.1210/edrv-14-5-632
更新日期:1993-10-01 00:00:00
abstract::It is well established that the organ damage that complicates human diabetes is caused by prolonged hyperglycemia, but the cellular and molecular mechanisms by which high levels of glucose cause tissue damage in humans are still not fully understood. The prevalent hypothesis explaining the mechanisms that may underlie...
journal_title:Endocrine reviews
pub_type: 杂志文章,评审
doi:10.1210/er.2014-1099
更新日期:2015-06-01 00:00:00
abstract::The etiology of the AITDs remains unclear but it is now generally believed that both genetic and environmental factors contribute to their development. Some recent findings have begun to directly and indirectly implicate the possibility of infectious agents in the pathogenesis of AITD, and these data serve as the basi...
journal_title:Endocrine reviews
pub_type: 杂志文章,评审
doi:10.1210/edrv-14-1-107
更新日期:1993-02-01 00:00:00
abstract::Hox genes have a well-characterized role in embryonic development, where they determine identity along the anteroposterior body axis. Hox genes are expressed not only during embryogenesis but also in the adult, where they are necessary for functional differentiation. Despite the known function of these genes as transc...
journal_title:Endocrine reviews
pub_type: 杂志文章,评审
doi:10.1210/er.2005-0018
更新日期:2006-06-01 00:00:00
abstract::Teeth are mineralized organs composed of three unique hard tissues, enamel, dentin, and cementum, and supported by the surrounding alveolar bone. Although odontogenesis differs from osteogenesis in several respects, tooth mineralization is susceptible to similar developmental failures as bone. Here we discuss conditio...
journal_title:Endocrine reviews
pub_type: 杂志文章,评审
doi:10.1210/er.2013-1009
更新日期:2014-02-01 00:00:00
abstract::During the past decade, possible advancement in timing of puberty has been reported in the United States. In addition, early pubertal development and an increased incidence of sexual precocity have been noticed in children, primarily girls, migrating for foreign adoption in several Western European countries. These ob...
journal_title:Endocrine reviews
pub_type: 杂志文章,评审
doi:10.1210/er.2002-0019
更新日期:2003-10-01 00:00:00
abstract::PRL and GH are hormones with a wide spectrum of actions. Specific receptors are widely distributed in a number of classical target organs, but other tissues that are not known targets also contain measurable binding sites or receptor mRNA. The most likely explanation is that PRL and GH cause effects that have not yet ...
journal_title:Endocrine reviews
pub_type: 杂志文章,评审
doi:10.1210/edrv-12-3-235
更新日期:1991-08-01 00:00:00
abstract::Human parturition is a complex process involving interactions between the myometrium and signals derived from the placenta, fetal membranes, and fetus. Signals originating from fetal membranes are crucial components that trigger parturition, which is clearly illustrated by the labor-initiating consequence of membrane ...
journal_title:Endocrine reviews
pub_type: 杂志文章,评审
doi:10.1210/er.2017-00188
更新日期:2018-06-01 00:00:00
abstract::The discovery of myostatin and our introduction to the "Mighty Mouse" over a decade ago spurred both basic and applied research and impacted popular culture as well. The myostatin-null genotype produces "double muscling" in mice and livestock and was recently described in a child. The field's rapid growth is by no mea...
journal_title:Endocrine reviews
pub_type: 杂志文章,评审
doi:10.1210/er.2008-0003
更新日期:2008-08-01 00:00:00