Abstract:
:17α-Ethinyl estradiol (EE), a synthetic analog of natural estrogen 17β-estradiol (E2), is extensively used in hormonal contraceptives and estrogen replacement therapy, and it has also been found in sewage effluents. Given that E2 is a well-known immunomodulator, surprisingly there has been only limited information on the cellular and molecular immunologic consequences of exposure to EE. To address this fundamental gap, we directly compared the effects of EE with E2 on splenic leukocytes of New Zealand Black × New Zealand White F1 progeny (NZB/WF1) mice during the preautoimmune period. We found that EE and E2 have common, as well as distinctive, immunologic effects, with EE exposure resulting in more profound effects. Both EE and E2 increased numbers of splenic neutrophils, enhanced neutrophil serine proteases and myeloperoxidase expression, promoted the production of nitric oxide and monocyte chemoattractant protein-1, and altered adaptive immune T cell subsets. However, activation of splenic leukocytes through the T cell receptor or Toll-like receptor (TLR)4 revealed not only common (IL-10), but also hormone-specific alterations of cytokines (IFNγ, IL-1β, ΤΝFα, IL-2). Furthermore, in EE-exposed mice, TLR9 stimulation suppressed IFNα, in contrast to increased IFNα from E2-exposed mice. EE and E2 regulated common and hormone-specific expression of immune-related genes. Furthermore, EE exposure resulted in more marked alterations in miRNA expression levels than for E2. Only EE was able to reduce global DNA methylation significantly in splenic leukocytes. Taken together, our novel data revealed that EE and E2 exposure confers more similar effects in innate immune system-related cell development and responses, but has more differential regulatory effects in adaptive immune-related cell development and responses.
journal_name
Endocrinologyjournal_title
Endocrinologyauthors
Dai R,Edwards MR,Heid B,Ahmed SAdoi
10.1210/en.2018-00824subject
Has Abstractpub_date
2019-01-01 00:00:00pages
101-118issue
1eissn
0013-7227issn
1945-7170pii
5166846journal_volume
160pub_type
杂志文章相关文献
ENDOCRINOLOGY文献大全abstract::Organ weight was compared in adult mice with deletion of one (IRS-1-/+) or both (IRS-1-/-) copies of the insulin receptor substrate-1 (IRS-1) gene and IRS-1+/+ littermates. IRS-1-/+ mice showed modest reductions in weight of most organs in proportion to a decrease in body weight. IRS-1-/- mice showed major reductions ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.140.12.7219
更新日期:1999-12-01 00:00:00
abstract::G protein-coupled receptor kinases (GRK 1-6) stimulate short-term desensitization (< 5 min) by phosphorylating G-protein coupled receptors, and also participate in receptor sequestration, which may relate to intermediate-term desensitization (30-60 min). The existence of such kinases and hence a potential role for the...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.137.9.8756570
更新日期:1996-09-01 00:00:00
abstract::Bisphenol A (BPA) is a ubiquitous endocrine-disrupting chemical. Developmental exposure produces changes in behavior and gene expression in the brain. Here, we examined social recognition behaviors in mice from the third familial generation (F3) after exposure to gestational BPA. Second-generation mice were bred in on...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2019-00196
更新日期:2019-08-01 00:00:00
abstract::We have previously reported that neurotensin (NT) is released from the small intestine and elevated in the hepatic-portal circulation in response to the perfusion of the small intestine with a micellar solution of oleic acid. In order to determine the minimum acyl chain length and whether the presence of a carboxylic ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-116-3-1133
更新日期:1985-03-01 00:00:00
abstract::Sertoli cells regulate differentiation and development of the testis and are essential for maintaining adult testis function. To model the effects of dysregulating Sertoli cell number during development or aging, we have used acute diphtheria toxin-mediated cell ablation to reduce Sertoli cell population size. Results...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2017-00196
更新日期:2017-09-01 00:00:00
abstract::GH controls its own secretion through a mechanism involving short-loop feedback regulation of the synthesis and release of GH-releasing hormone (GHRH). GHRH neurons coexpress the peptide galanin, but the functional significance of this coexpression is unknown. In this study, we tested the hypotheses that 1) galanin ge...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.137.12.8940350
更新日期:1996-12-01 00:00:00
abstract::Synthetic glucocorticoids (GCs), including dexamethasone (DEX), are powerful anti-inflammatory drugs. Long-term use of GCs, however, can result in metabolic side effects such as hyperglycemia, hepatosteatosis, and insulin resistance. The GC receptor (GR) and liver X receptors (LXRα and LXRβ) regulate overlapping genes...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2017-00094
更新日期:2017-04-01 00:00:00
abstract::Adipose tissue secretes a variety of bioactive signaling molecules, termed adipokines, which regulate numerous biological functions including appetite, energy balance, glucose homeostasis, and inflammation. Chemerin is a novel adipokine that regulates adipocyte differentiation and metabolism by binding to and activati...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2011-1490
更新日期:2012-02-01 00:00:00
abstract::Leydig cells from mature rat testes contain high levels of 11 beta-hydroxysteroid dehydrogenase (11HSD), an enzyme that oxidatively inactivates glucocorticoids. We have proposed that the 11HSD of Leydig cells protects the testis from the effects of high levels of glucocorticoids, as may occur in stress and Cushing's d...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.134.3.8119160
更新日期:1994-03-01 00:00:00
abstract::Basal serum gonadotropin levels were monitored weekly in female hamsters from birth to 10 weeks of age. Hamsters raised on three different photoperiods presented uniform pre- and postpubertal patterns of serum LH and FSH, suggesting that gonadotropin release in the young hamster occurs independently of ambient photope...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-110-4-1262
更新日期:1982-04-01 00:00:00
abstract::Experiments were carried out to characterize the prolactin stimulation of labeled uridine uptake into mammary gland explants which were initially preincubated for 2 days in medium containing insulin plus hydrocortisone. Prolactin was found to enhance labeled uridine uptake after 4 h but not after 2 h when uridine conc...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-96-5-1307
更新日期:1975-05-01 00:00:00
abstract::A RT-PCR approach was used to clone and sequence the full-length growth hormone receptor (GHR) of a teleost fish, the turbot (Scophthalmus maximus). Total liver RNA was amplified by RT-PCR with degenerate primers designed in extracellular and cytoplasmic regions, and a single DNA fragment of 1100 bp was obtained. The ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.142.7.8407
更新日期:2001-07-01 00:00:00
abstract::Preincubation of rat pituitary cells in primary culture with rat GH-releasing factor (rGRF) resulted in substantial desensitization to subsequent GRF stimulation. rGRF-directed GH release and intracellular cAMP accumulation decreased in the desensitized cells. Whereas prior treatment of rat pituitary cells caused part...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-116-4-1334
更新日期:1985-04-01 00:00:00
abstract::The regulatory role of cAMP-dependent protein kinase in steroidogenesis was examined in luteal cell mitochondria prepared from heavily luteinized prepubertal rat ovaries. The cAMP-dependent protein kinase, localized in luteal mitochondria, comprised 5.5% of the total cellular protein kinase activity (cAMP-dependent). ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-117-1-315
更新日期:1985-07-01 00:00:00
abstract::The atrial natriuretic peptide (ANP) gene is expressed in several extraatrial tissues in which ANP may be involved in the regulation of autocrine or paracrine functions. In the ovary, the synthesis of ANP, its binding sites, and a physiological role were found. The ANP system in the oviduct, however, is yet to be defi...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.138.6.5160
更新日期:1997-06-01 00:00:00
abstract::The expression of cholesterol side-chain cleavage cytochrome P450 (P450scc), 17 alpha-hydroxylase cytochrome P450 (P45017 alpha), and 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) was studied in bovine placenta and fetal adrenal glands throughout gestation. The levels of expression of these enzymes were much lower ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.130.5.1374010
更新日期:1992-05-01 00:00:00
abstract::TRH is a potent stimulator of pituitary TSH release, but its function in the physiological regulation of thyroid activity is still controversial. The purpose of the present study was to investigate TRH and catecholamine secretion into hypophysial portal blood of hypothyroid and hyperthyroid rats, and in rats bearing p...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-123-1-523
更新日期:1988-07-01 00:00:00
abstract::Cyclin D1 encodes the regulatory subunit of a holoenzyme that phosphorylates and inactivates the retinoblastoma protein and promotes progression through the G1-S phase of the cell cycle. Amplification or overexpression of cyclin D1 plays pivotal roles in the development of a subset of human cancers including parathyro...
journal_title:Endocrinology
pub_type: 杂志文章,评审
doi:10.1210/en.2004-0959
更新日期:2004-12-01 00:00:00
abstract::Kallikreins are a multigene subfamily of serine proteases that may have a role in processing precursors of polypeptide hormones and growth factors. The epidermal growth factor (EGF) immunoreactivity in mouse milk is derived from the membrane-bound EGF precursor located on the lumenal border of the alveolar cells in th...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.135.5.7525260
更新日期:1994-11-01 00:00:00
abstract::LPXRFamide (LPXRFa) peptides have been characterized for their ability to inhibit gonadotropin (GTH) release in birds and stimulate growth hormone (GH) release in frogs. However, their involvement in regulating the reproductive hypothalamo-pituitary-gonadal axis in mammals and fish is inconclusive. To study the role o...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2013-2047
更新日期:2014-11-01 00:00:00
abstract::There are many precedents for the production from a single precursor of multiple peptides, with independent receptors and different bioactivities. Gastrin-releasing peptide (GRP) is initially synthesized as amino acids 1-27 of a 125-residue precursor, proGRP, and is subsequently cleaved and amidated to form GRP18-27. ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2006-0466
更新日期:2007-03-01 00:00:00
abstract::GnRH autoregulates GnRH neurons through an ultrashort feedback loop. One potential mechanism is the regulation of K(+) channel activity through the GnRH receptor. Whereas GnRH inhibits the activity of the M-current in peripheral neurons, there is no direct evidence that the M-current is involved in the autoregulatory ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2007-1178
更新日期:2008-05-01 00:00:00
abstract::Angiotensin II is a potent octapeptide vasoconstrictor and regulator of cardiovascular and electrolyte homeostasis. Angiotensinogen, the protein precursor of angiotensin II, is synthesized by the liver and many other organs of the adult rat. To determine whether angiotensin may be present in early fetal development we...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-121-4-1335
更新日期:1987-10-01 00:00:00
abstract::Exposure to estrogens is associated with an increased risk of developing breast, cervical, and liver cancer. Estrogens strongly induce the human granzyme B inhibitor, proteinase inhibitor 9 (PI-9). Because cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells use the granzyme pathway to induce apoptosis of targ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2005-0996
更新日期:2006-03-01 00:00:00
abstract::The effects of FFA on circulating LH and GH concentrations in ovariectomized ewe lambs were investigated. Lambs (n = 14) were weaned at 2.5 months, ovariectomized at 6.5 months, and used at 8.5 months of age. From weaning until day 0 of the experiment, lambs were fed to maintain body weights (23 kg). On day 0, serum F...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-126-4-1934
更新日期:1990-04-01 00:00:00
abstract::We have recently reported evidence for the presence of stereospecific energy-dependent transport processes for T3 in rat tissues. These processes were responsible for maintenance of concentration differences of free L- and D-T3 across the cellular plasma and nuclear membranes. In rat liver, the free L-T3 concentration...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-117-6-2449
更新日期:1985-12-01 00:00:00
abstract::Sclerostin (SOST), a member of the cystine-knot superfamily, is essential for proper skeletogenesis because a loss-of-function mutation in the SOST gene results in sclerosteosis featured with massive bone growth in humans. To understand the function of SOST in developmental skeletal tissue formation, we examined SOST ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2003-1492
更新日期:2004-10-01 00:00:00
abstract::Specific binding of human chorionic gonadotropin (hCG), and the hCG-sensitive adenyl cyclase of granulosa cells from small (1-2 mm), medium (3-5 mm), and large (6-12 mm) porcine ovarian follicles have been studied. The number of hCG-binding sites per cell (n) increases during follicle maturation without a change in th...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-99-1-42
更新日期:1976-07-01 00:00:00
abstract::Up to now, no relevant tumor antigen has been identified in medullary thyroid carcinoma (MTC). The aim of the present study was to prove the concept of an immunization with an amino acid-modified calcitonin (CT) for the treatment of MTC in a transgenic mouse model. Amino acid-modified (human) CT has been chosen for va...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2008-0631
更新日期:2008-11-01 00:00:00
abstract::The family of CRH-related peptides are suggested to play important roles in the control of myometrial contractility during pregnancy and labor. In this study we investigated the expression of urocortin II (UCN II) in human myometrium and its ability to phosphorylate intracellular components that can be involved in mod...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2003-1210
更新日期:2004-02-01 00:00:00