Abstract:
:Amiodarone, a potent antiarrhythmic drug, contains 37.2% iodine by weight and may induce either hypo- or hyperthyroidism. The high iodine content of amiodarone may be responsible for both complications, but a cytotoxic effect of the drug on the thyroid resulting in thyroiditis has been reported. In the present study the cytotoxic effect of amiodarone was evaluated in three culture systems with different biological properties: 1) a strain of rat thyroid cells (FRTL-5 cells) that maintains most differentiated functions of normal thyroid cells, including an active iodide pump, but an inability to organify iodide; 2) a line of Chinese hamster ovary (CHO) fibroblasts; and 3) freshly prepared primary cultures of human thyroid follicles (hTF) that trap and organify iodide. Cells were radiolabeled with 51Cr and incubated for 24 h with medium alone, medium plus amiodarone (3.75-200 microM), medium plus an iodinated radiographic contrast agent (sodium diatrizoate; 7.5-200 microM), or medium plus potassium iodide (7.5-300 microM). At concentrations ranging from 75-200 microM, amiodarone induced a significant and dose-dependent release of 51Cr in FRTL-5 cells. In contrast, diatrizoate or KI had no cytotoxic effect on FRTL-5 cells. In the same molar concentrations, amiodarone was also cytotoxic in CHO cells. In hTF, the release of 51Cr produced by amiodarone occurred at a lower concentration (37.5 vs. 75 microM) and was significantly greater than that in FRTL-5 cells. The cytotoxic effect of amiodarone in hTF was partially, but significantly, reduced by methimazole, an inhibitor of iodide organification. In the FRTL-5 cell culture system, amiodarone also produced a dramatic inhibition of TSH-stimulated cell growth. This growth-inhibiting effect of amiodarone was evident at low concentrations (3.75-7.5 mumol/liter) of the drug, which did not produce significant cytotoxicity. In conclusion, 1) amiodarone had a cytotoxic effect in CHO fibroblasts, a nonthyroid cell line; 2) this cytotoxic effect occurred in thyroid cells independent of their ability to organify iodide; 3) however, the toxic effect of amiodarone was greater and occurred at a lower molar concentration in freshly prepared human thyroid follicles that trap and organify iodide; and 4) in the latter culture system, methimazole, an inhibitor of iodide organification, partially, but significantly, reduced the cytotoxic effect of amiodarone. These data suggest that thyroid cytotoxicity produced by amiodarone is mainly due to a direct effect of the drug on thyroid cells, but excess iodide released from the drug may contribute to its toxic action.
journal_name
Endocrinologyjournal_title
Endocrinologyauthors
Chiovato L,Martino E,Tonacchera M,Santini F,Lapi P,Mammoli C,Braverman LE,Pinchera Adoi
10.1210/endo.134.5.8156930subject
Has Abstractpub_date
1994-05-01 00:00:00pages
2277-82issue
5eissn
0013-7227issn
1945-7170journal_volume
134pub_type
杂志文章相关文献
ENDOCRINOLOGY文献大全abstract::Women with polycystic ovary syndrome (PCOS) and hyperandrogenism have altered hormone levels and suffer from ovarian dysfunction leading to subfertility. We have attempted to generate a model of hyperandrogenism by feeding mice chow supplemented with dehydroepiandrosterone (DHEA), an androgen precursor that is often e...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2012-2140
更新日期:2013-12-01 00:00:00
abstract::A plasma fraction rich in thyroid hormone-binding globulin (hTBG, human thyropexin) was injected iv into rabbits in order to see whether thyroid hormone concentrations in plasma would increase by return of T3 and T4 from the extravascular space. For this purpose, both [125I]T3 and [131I]T4 were simultaneously injected...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-124-3-1428
更新日期:1989-03-01 00:00:00
abstract::Mouse uterine estrogen receptor (ER) was purified about 11,000-fold from normal mouse uteri by affinity chromatography. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the purified ER demonstrated a major component of 65,000 mol wt with minor fragments of the 54,000- and 37,000-dalton species, as judged b...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-121-6-2099
更新日期:1987-12-01 00:00:00
abstract::Sulfonylureas are drugs widely used in the treatment of patients with type 2 diabetes mellitus. In addition to their pancreatic effect of stimulating insulin secretion, many studies suggest that sulfonylureas also have extrapancreatic actions. We have previously reported that gliclazide, a second-generation sulfonylur...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2003-0755
更新日期:2004-02-01 00:00:00
abstract::The establishment of dominant ovarian follicles that are capable of ovulating fertilizable oocytes is a fundamental determinant of female fertility. This process is governed by pituitary gonadotropins as well as local ovarian factors. Within the follicle, estrogen acts in an autocrine/paracrine manner to enhance FSH a...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2005-0349
更新日期:2005-08-01 00:00:00
abstract::We have investigated the ability of fetal rat skin to heal an excisional wound in vitro. Skin from the backs of E17-E19 rats was wounded using a 1-mm diameter cutting needle and suspended in culture on a 6-pin cradle for 72 h. Neither contraction nor epithelial closure was observed within wounds created in skin from E...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.138.9.5357
更新日期:1997-09-01 00:00:00
abstract::We have investigated the interaction of estrogen with GnRH on the regulation of LH subunit mRNA in female hypogonadal (hpg) mice receiving constant frequency and amplitude pulsatile GnRH treatment for up to 18 days. The level of cytosolic common alpha mRNA in female hpg mouse pituitaries was 45 +/- 6% of normal female...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-124-4-1744
更新日期:1989-04-01 00:00:00
abstract::This report describes properties of highly purified cathepsin-B and an additional cysteine proteinase, designated cysteine proteinase I, obtained from human thyroids. Both enzymes are localized to lysosomes. The activity profile of cysteine proteinase I combined with its sensitivity to the active site inhibitor Z-Phe-...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-123-2-1089
更新日期:1988-08-01 00:00:00
abstract::The human breast cancer cell line MCF-7 responds to estrogens with increased progesterone receptor (PR) levels. In this study, we use dense amino acid density shift analyses to address directly the question of whether estrogen increases PR levels in MCF-7 cells by altering rates of receptor synthesis and/or degradatio...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-122-3-935
更新日期:1988-03-01 00:00:00
abstract::Term pregnancy human placenta contains hCG/LH receptor mRNA transcripts and immunoreactive receptor protein. Both the receptor transcripts and receptor proteins are present only in trophoblasts. These findings led us to investigate whether hCG can regulate its own synthesis in term pregnancy human placenta. Treatment ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.133.6.8243330
更新日期:1993-12-01 00:00:00
abstract::We have studied the long-term effects of nicotinamide (NIC) on the synthesis of NO by insulin producing cells. NIC delays the formation of nitrite by interleukin (IL)-1 beta-(IL-1, 25 U/ml)-stimulated RINm5F cells, and previous exposure of cells to IL-1 for 15 h prevents this effect. The delay is associated with a lac...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.137.11.8895350
更新日期:1996-11-01 00:00:00
abstract::Pheochromocytomas (PCCs) are tumors arising from neural crest-derived chromaffin cells. There are currently few animal models of PCC that recapitulate the key features of human tumors. Because such models may be useful for investigations of molecular pathomechanisms and development of novel therapeutic interventions, ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2016-1108
更新日期:2016-08-01 00:00:00
abstract::The estrogen-induced and -dependent Syrian hamster renal tumor is the most intensively studied model in estrogen carcinogenesis. Yet, it remains confounding that the kidney of this species behaves as an estrogen target tissue. As both reproductive and urinary systems arise from the same germinal ridge, we propose that...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.142.9.8355
更新日期:2001-09-01 00:00:00
abstract::Native PRL and des-amido forms 1, 2, and 3 were tested for their individual immunochemical and receptor-binding abilities. The results show that deamidation of either secreted mouse PRL or stored ovine PRL alters their binding in a radioreceptor assay. For each accumulated deamidation there was a statistically signifi...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-116-1-353
更新日期:1985-01-01 00:00:00
abstract::The perinatal rat exhibits low serum TSH levels in the presence of very low concentrations of T3 and T4. We had reported previously that this animal does not require endogenous TRH for TSH release. We investigated here whether the inhibitory hormone somatostatin (SS) has a role in maintaining the low TSH secretory set...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-117-4-1683
更新日期:1985-10-01 00:00:00
abstract::Although renal hypertrophy occurs rapidly after uninephrectomy, restoring the majority of renal excretory function, it remains unknown whether similar compensatory mechanisms maintain 1,25-dihydroxyvitamin D production (and calcium homeostasis). To address this issue we compared plasma calcitriol levels and renal 25-h...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-124-5-2118
更新日期:1989-05-01 00:00:00
abstract::Maternal nutrition can affect the susceptibility of the offspring to metabolic disease later in life, suggesting that this period is a window of opportunity for intervention to reduce the risk of metabolic disease. Resveratrol, a natural polyphenol, has a wide range of beneficial properties including anti-obesogenic, ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endocr/bqaa090
更新日期:2020-08-01 00:00:00
abstract::Transfer of corticosterone from serum to milk was studied in lactating rats after ether and pentobarbital anesthesia. Two minutes after the onset of anesthesia stress, total serum and milk corticosterone concentrations were not significantly different. By 30 min, corticosterone concentrations in serum increased to a p...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-115-4-1364
更新日期:1984-10-01 00:00:00
abstract::Stress-responsive neurons of the hypothalamic paraventricular nucleus (PVN) show functional plasticity and adapt to repeated restraint (RR) stress. To investigate whether neuronal adaptation to the homotypic stress also affects their response to a heterotypic stressor, we used in situ hybridization with intronic and e...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.140.8.6943
更新日期:1999-08-01 00:00:00
abstract::The antithyroid drug 6-propylthiouracil (PTU) was previously shown in our laboratory to have an unexpectedly prolonged inhibitory effect on iodination in the thyroid glands of rats. Eighteen hours after injection of a relatively small dose, iodination in the thyroid remained inhibited by more than 90%. We previously s...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-124-6-3038
更新日期:1989-06-01 00:00:00
abstract::GnRH neurons are regulated by hypothalamic kisspeptin neurons. Recently, galanin was identified in a subpopulation of kisspeptin neurons. Although the literature thoroughly describes kisspeptin activation of GnRH neurons, little is known about the effects of galanin on GnRH neurons. This study investigated whether gal...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2016-1064
更新日期:2016-08-01 00:00:00
abstract::The study of epigenetics allows for the understanding of gene × environmental interactions and provides a mechanism by which brief internal or external environmental changes can shape lasting differences in gene function and behavior. Epigenetic processes appear to impact a wide variety of physiological processes with...
journal_title:Endocrinology
pub_type: 杂志文章,评审
doi:10.1210/en.2010-0793
更新日期:2011-02-01 00:00:00
abstract::We examined the effects of the polycationic antibiotic, neomycin, on the function of dispersed bovine parathyroid cells. Neomycin caused a reversible, dose-dependent inhibition of low calcium (Ca++)-stimulated PTH release, with half-maximal inhibition at 30 microM. Maximal inhibition (with 200 microM neomycin) was not...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-128-6-3047
更新日期:1991-06-01 00:00:00
abstract::Activins and transforming growth factor-beta (TGF beta) are crucial autocrine, paracrine, and endocrine modulators of anterior pituitary function. Activins regulate most pituitary cells and lactotropes are targets of TGF beta. Smad2 and Smad3 are two cellular mediators of activin/TGF beta signaling, whereas Smad7 is a...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.142.3.8028
更新日期:2001-03-01 00:00:00
abstract::Removal of fetuses at day 14 of gestation (Ftx14) in the pregnant rat leads to a marked suppression of serum levels of rat placental lactogen (rPL-II). One might attribute this to compromised placental growth in the absence of a fetus. However, if ovariectomy and fetectomy (Ftx14 Ovx14) are carried out at the same tim...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-114-1-22
更新日期:1984-01-01 00:00:00
abstract::GH is secreted in a pulsatile manner, the pattern of which plays an important role in the regulation of growth and metabolism. Sex steroids are also known to participate in metabolic regulation. The present study was undertaken to elucidate the relationship between changes in GH pulsatility and metabolic transition du...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2004-1434
更新日期:2005-06-01 00:00:00
abstract::Berberine, a hypoglycemic agent, has recently been shown to activate AMP-activated protein kinase (AMPK) contributing to its beneficial metabolic effects in peripheral tissues. However, whether berberine exerts a regulatory effect on beta-cells via AMPK or other signaling pathways and counteracts glucolipotoxicity rem...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2007-1752
更新日期:2008-09-01 00:00:00
abstract::The lateral hypothalamic area (LHA) is essential for motivated ingestive and locomotor behaviors that impact body weight, yet it remains unclear how the neurochemically defined subpopulations of LHA neurons contribute to energy balance. In particular, the role of the large population of LHA neurotensin (Nts) neurons h...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2018-00311
更新日期:2018-09-01 00:00:00
abstract::Tumor necrosis factor-alpha (TNF alpha), a product of activated monocytes, induces tissue wasting in certain solid tumors in vivo and in in vitro model systems. Recent studies indicate that TNF alpha also regulates cell replication and expression of differentiated function in a variety of nonneoplastic cell systems. S...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-123-3-1442
更新日期:1988-09-01 00:00:00
abstract::Permanent effects of postnatal gonads on dopamine (DA)-mediated regulation of PRL secretion were examined in adult male rats of the Wistar-Imamichi strain. Rats were bilaterally orchidectomized at varying postnatal days, i.e. 8 h after birth [neonatal castration (NC)] or at 1, 2, 3, 4, or 6 weeks of age, and subjected...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-120-6-2205
更新日期:1987-06-01 00:00:00