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Query: UMLS:C0338671 (Steroids)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thyroid dysfunction in humans is known to alter the excretory pattern of estrogen metabolites, suggesting that thyroid hormone directly influences the oxidative metabolism of estradiol. We examined the extent to which a brief period of hyperthyroidism specifically affected estradiol hydroxylation at C-2 and C-16 alpha, the two primary and competing sites of estrogen oxidation, using an in vivo radiometric assay in healthy male volunteers. Hydroxylation at C-2 was increased by a 2-week course of thyroxine (4.3 micrograms/kg/d) from 29.9% +/- 2.6% to 35.9% +/- 3.1% (P = 0.04), while 16 alpha-hydroxylation was unchanged (10.3% +/- 0.8% versus 9.3% +/- 0.5%). The greater extent of oxidation at C-2 was evidenced by a twofold increase in the urinary excretion of 2-hydroxyestrone (2.88 +/- 0.32 versus 5.30 +/- 0.85 micrograms/g creatinine), while the excreted products of 16 alpha-hydroxylation were unchanged. At the same time, significant reductions in total cholesterol (173.8 +/- 7.9 versus 139.4 +/- 8.9 mg/dl), low-density lipoprotein cholesterol (110.0 +/- 5.3 versus 83.8 +/- 7.7 mg/dl), and apolipoprotein B (68.2 +/- 3.3 versus 53.1 +/- 3.6 mg/dl) were observed. Serum levels of estrone, estradiol, sex hormone-binding globulin, high-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, triglycerides, and apolipoprotein A-I were not significantly affected. This study adds to the growing evidence that catechol estrogen production in humans is more readily regulated than 16 alpha-hydroxylation, which is relatively refractory to treatment.
Steroids 1990 Jan
PMID:Effects of exogenous thyroxine on C-2 and C-16 alpha hydroxylations of estradiol in humans. 230 54

Estrogen treatment affects the hepatic synthesis and/or secretion of several proteins involved in clinically important pathological processes such as atherosclerosis, hypertension, and thrombosis. The endocrine regulation of the estrogen receptor (ER) concentration in primary cultures of rat hepatocytes was studied. Human growth hormone (hGH) and dexamethasone (DEX) in combination increased ER concentration 6-fold and ER mRNA levels 2.5-fold. These effects were not significantly different from those observed after treatment with the purely somatogenic bovine growth hormone (GH) in combination with DEX. Treatment with the lactogen ovine prolactin in the presence or absence of DEX did not significantly affect ER or ER mRNA concentrations. Triiodothyronine treatment at the most effective concentration (50 nM) increased ER and ER mRNA levels twofold. Medium supplementation with estradiol (0.1 nM) throughout the experiment did not affect the response to treatment with hGH and DEX. Treatment with high concentrations of ethinylestradiol in combination with hGH and DEX, however, increased the ER level twice as much as hGH and DEX without addition of estradiol or ethinylestradiol, whereas the ER mRNA concentration was the same in both the GH+DEX group and GH+ DEX+ (estradiol or ethinylestradiol) groups. These data indicate the importance of GH in combination with glucocorticoids for the maintenance of ER concentrations in the rat liver. Thyroid hormones may be of some, although minor importance, whereas the data suggest that prolactin is not directly involved in hepatic ER regulation.
Steroids 1997 Oct
PMID:Hormonal regulation of the estrogen receptor in primary cultures of hepatocytes from female rats. 938 11

A 43-year-old woman with Hashimoto's thyroiditis (HT), euthyroid on levothyroxine since 1999, developed thyroid-associated ophthalmopathy (TAO) in February 2002. She had involvement of the eye muscles, as shown by computed tomography (CT) scan. She was started on methylprednisolone pulse therapy 7.5 mg/kg of body weight, (one cycle every 2 weeks, each cycle comprising two infusions on alternate days), with rapid improvement of soft tissue inflammation and of eye motility, as confirmed by the reduction of clinical activity score (CAS) and eye muscles size on CT scan. At the end of treatment the patient showed a marked and rapid increase of serum aminotransferases (up to 1200 U/L). She had negative hepatitis A, B, and C viruses serology, but circulating antinuclear antibodies. A liver biopsy, performed at 4 weeks after the discontinuation of intravenous steroids, led to the diagnosis of autoimmune hepatitis (AIH). The patient was treated with oral steroids with a rapid reduction of serum aminotransferases concentrations. To our knowledge, there have been only two reports of liver dysfunction after intravenous steroids for TAO, but the etiology of such hepatitis had not been established. AIH may develop in patients with multiple autoimmunity and may not become overt until immune rebound occurs (i.e. after cessation of or between immunosuppressive treatment cycles). Steroids are the first line of treatment for AIH, hence their use would not be contraindicated when patients with TAO have chronic hepatitis, provided that the modalities of treatment are appropriate.
Thyroid 2004 Aug
PMID:Onset of autoimmune hepatitis during intravenous steroid therapy for thyroid-associated ophthalmopathy in a patient with Hashimoto's thyroiditis: case report. 1532 Sep 78

Extranuclear or nongenomic effects of thyroid hormones do not require interaction with the nuclear receptor, but are probably mediated by specific membrane receptors. This review will focus on the extranuclear effects of thyroid hormones on plasma membrane transport systems in non mammalian cells: chick embryo hepatocytes at two different stages of development, 14 and 19 days. At variance with mammals, the chick embryo develops in a closed compartment, beyond the influence of maternal endocrine factors. Thyroid hormones inhibit the Na+/K+-ATPase but stimulate the Na+/H+ exchanger and amino acid transport System A with different dose-responses: a bell-shaped curve in the case of the exchanger and a classic saturation curve in the case of System A. These effects are mimicked by the analog 3,5-diiodothyronine. Signal transduction is mediated by interplay among kinases, mainly protein kinase C and the MAPK pathway, initially primed by second messengers such as Ca2+, IP3, and DAG as in mammalian cells. Thyroid hormones and 3,5-diiodothyronine stimulate thymidine incorporation and DNA synthesis, associated with the increased levels and activity of cyclins and cyclin-dependent kinases involved in the G1/S transition, and also these effects have their starting point at the plasma membrane. Increasing evidence now demonstrates that thyroid hormones act as growth factors for chick embryo hepatocytes and their extranuclear effects are important for prenatal development and differentiation.
Steroids
PMID:Short-term effects of thyroid hormone in prenatal development and cell differentiation. 1586 27

Thyroid hormone nuclear receptors (TRs) mediate the biological activities of the thyroid hormone (T3) in growth, development and differentiation and in the maintenance of metabolic homeostasis. They are derived from two separate genes to yield four major T3-binding isoforms: alpha1, beta1, beta2, and beta3. To understand whether TR isoforms mediate specific functions in vivo, PV mutation, identified from a patient with resistance to thyroid hormone (RTH), was targeted to the TRbeta (TRbetaPV mice) or TRalpha gene (TRalpha1PV mice). PV has a frame-shift mutation in the last 14 carboxyl-terminal amino acids of TRbeta1 or TRalpha1, resulting in the loss of T3-binding and transcriptional activities. TRbetaPV mice faithfully reproduce human RTH with dysfunction of the pituitary-thyroid axis, impairment in weight gain and accelerated bone development, hearing defects, abnormal regulation of serum cholesterol and increased physical activity reminiscent of attention deficit-hyperactivity disorder. In contrast, TRalpha1PV mice show no abnormalities in the pituitary-thyroid axis and other discernable RTH phenotypes. In addition, TRalpha1PV mice are dwarfs with high mortality, reduced fertility and survival, reduced glucose utilization in the brain and marked delay in bone development. These results clearly show that the molecular actions of TRalpha1PV are distinct from those of TRbetaPV in vivo. Further studies indicate that these contrasting phenotypes are mediated by distinct isoform-dependent abnormal regulation of T3-target genes in tissues. Thus, these two mutant mice provide a valuable tool for further dissecting the molecular bases of isoform-dependent actions of mutant TRs in vivo and their roles in disease.
Steroids
PMID:Isoform-dependent actions of thyroid hormone nuclear receptors: lessons from knockin mutant mice. 1586 29

Gonadotropins cause immediate chloride secretion in Leydig cells, which still have an unknown physiological. Thyroid and Leydig cells produce more cAMP and steroids, respectively, under low or chloride-free conditions. Here, we show that chloride efflux mediated by incubation of Mouse Leydig Tumor cells (MLTC-1) in hypotonic or chloride-free isotonic buffers results in more cAMP production without any gonadotropic stimulation. MLTC-1 cells incubated with 0.5mM diphenylamine-2-carboxylate (DPC), a chloride efflux inhibitor, produced increased amounts of testosterone as chloride ions were substituted by gluconate or sulphate ions under isotonic conditions. There was also an up-regulation of steroidogenic acute regulatory protein and 3beta-hydroxysteroid dehydrogenase/isomerase type I mRNAs, without human chorionic gonadotropin. With the exception of cAMP production, 2mM DPC inhibited all of the above, including the transcription of constitutively expressed cholesterol side-chain cleavage enzyme and the L19 house-keeping gene. Although it was speculated that gonadotropin mediated chloride secretion could aid steroid hormone release, we conclude that the real reason for chloride secretion in Leydig cells may be to "kick start" cAMP production.
Steroids 2005 Aug
PMID:Chloride efflux in unstimulated Leydig cells causes autonomous cAMP production and stimulatory/inhibitory steroidogenesis with an efflux inhibitor. 1591 86

Graves' Disease (GD) is the most common cause of juvenile thyrotoxicosis in children and adolescents. Regarding its treatment, there are wide differences between individual physicians' regimes and those of physicians in different countries. While Antithyroid Drugs (ATDs) remain the initial treatment of choice in almost all the medical centers in Europe, with surgery used mainly to deal with antithyroid failures, there is increasing interest, especially in US, in the use of radioiodine. Although there are data reporting no significant increase in thyroid neoplasia or gonadal injury in older children and adults receiving outpatient doses of radioiodine, endocrinologists and parents continue to shy away from this therapy, especially in Europe, in young children. Nor is there any increase in congenital abnormalities in the offspring of the adults. Thyroid Eye Disease (TED) is one of the most common manifestations of GD, the pathophysiology of which is not very well understood. However, studies by several investigators have begun to shed light on the many complex factors contributing to the development of ocular symptoms in TED. Thyroid ophthalmopathy in juvenile GD is more common but less severe and more likely to remit completely. Steroids and decompression surgery will very rarely be needed in early childhood. It has to be kept in mind that prolonged prednisone administration, which should be used in some severe cases of TED, is associated with weight gain, immune suppression and growth failure in children. Recent studies have shown successful therapy with the long-acting somatostatin analogues (SM-a), octreotide and lanreotide in adult patients with active TED. The rationale of this therapy is based on recent studies in which somatostatin receptors have been identified within the orbital tissues in TED, both in vitro and in vivo. We recently had the opportunity to treat 3 adolescents with moderately severe TED with SM-a. All had increased clinical activity scores (CAS) and were euthyroid on ATD at the time of initiation of treatment. They received 20 mg octreotide (sandostatin- LAR) i.m. one injection every 30 days for 4 months. Their ophthalmopathies improved substantially and CAS decreased in all the patients. In view of the encouraging therapeutic results in these 3 pediatric patients, SM-a may prove to be a valuable treatment in juvenile ophthalmopathy and a good alternative to corticosteroids. The results using SM-a in the treatment of TED seem promising, but studies with larger numbers of patients are needed before we reach any final conclusions.
 ...
PMID:Ophthalmic complications in juvenile Graves' Disease - clinic and therapeutic approaches. 1644 62

Thyroid hormone (l-thyroxine, T(4), or 3,5,3'-triiodo-l-thyronine, T(3)) treatment of human papillary and follicular thyroid cancer cell lines resulted in enhanced cell proliferation, measured by proliferating cell nuclear antigen (PCNA). Thyroid hormone also induced activation of the Ras/MAPK (ERK1/2) signal transduction pathway. ERK1/2 activation and cell proliferation caused by thyroid hormone were blocked by an iodothyronine analogue, tetraiodothyroacetic acid (tetrac), that inhibits binding of iodothyronines to the cell surface receptor for thyroid hormone on integrin alphaVbeta3. A MAPK cascade inhibitor at MEK, PD 98059, also blocked hormone-induced cell proliferation. We then assessed the possibility that thyroid hormone is anti-apoptotic. We first established that resveratrol (10 microM), a pro-apoptotic agent in other cancer cells, induced p53-dependent apoptosis and c-fos, c-jun and p21 gene expression in both papillary and follicular thyroid cancer cells. Induction of apoptosis by the stilbene required Ser-15 phosphorylation of p53. Resveratrol-induced gene expression and apoptosis were inhibited more than 50% by physiological concentrations of T(4). T(4) activated MAPK in the absence of resveratrol, caused minimal Ser-15 phosphorylation of p53 and did not affect c-fos, c-jun and p21 mRNA abundance. Thus, plasma membrane-initiated activation of the MAPK cascade by thyroid hormone promotes papillary and follicular thyroid cancer cell proliferation in vitro.
Steroids 2007 Feb
PMID:Thyroid hormone is a MAPK-dependent growth factor for thyroid cancer cells and is anti-apoptotic. 1717 66

Thyroid hormone (TH) is essential for neuronal migration and synaptogenesis in the developing brain. Assembly of neuronal circuits depends on guidance cues provided by the extracellular matrix. These cues are interpreted by the migrating neuron and its growing neurites through transmembrane signaling proteins anchored in place by the actin cytoskeleton. One of the best examples of a non-genomic action of thyroid hormone is its dynamic regulation of the number and quantity of actin fibers in astrocytes. Thyroxine (T4) and its transcriptionally inactive metabolite, 3',5',3-triiodothyronine (reverse T3) are responsible for modulating microfilament organization, while the transcriptional activator, 3',3,5-triiodothyronine (T3) is inert. The biological consequence of the loss of the actin filaments in astrocytes is the inability of the cell to anchor laminin, to its cell surface, and the loss of this key guidance molecule interrupts neurite pathfinding and neuronal migration. These data provide the essentials to construct a physiological pathway where TH-dependent regulation of the polymerization state of actin in the astrocyte and the developing neuron modulates the production and recognition of guidance cues--cues that if disrupted lead to abnormal neuronal migration and neuronal process formation--and lead to the morphological deficits observed in the cretinous brain.
Steroids 2008 Oct
PMID:Non-genomic actions of thyroid hormone in brain development. 1828 May 26

Confocal microscopy and cell fractionation studies have revealed the residence of nuclear thyroid hormone receptors (TR) in cytoplasm. Treatment of cells with the hormone (L-thyroxine or 3,5,3'-triiodo-L-thyronine, T(3)) results in shuttling of TR into the nuclear compartment. Confocal microscopy has also disclosed that TR in the nuclear compartment is redistributed in response to exposure of cells to iodothyronine. The TRbeta1 isoform may be found in cytoplasm of thyroid hormone-treated cells complexed with other proteins, such as mitogen-activated protein kinase (MAPK), the p85 regulatory subunit of phosphatidylinositol 3-kinase (PI 3-K) and nuclear receptor coactivators. Formation of such complexes may facilitate nuclear import of TR and initiate specific gene transcription (PI 3-K) or cell proliferation (MAPK). Nuclear retention of TRalpha1 is also increased by T(3). It is not clear that iodothyronines have primary effects on nuclear export of TRs. Thyroid hormone may also increase cytoplasm-to-nucleus partitioning of p53 and certain signal-transducing pathway proteins. A monomer derived from the cell surface receptor for thyroid hormone on integrin alphavbeta3 that does not share homologies with TR may move to the cell nucleus in thyroid hormone-treated cells. Because cells in the intact organism are tonically exposed to thyroid hormone, the latter is likely to contribute to the basal rate of nuclear import of thyroid hormone receptors.
Steroids 2008 Oct
PMID:Promotion by thyroid hormone of cytoplasm-to-nucleus shuttling of thyroid hormone receptors. 1832 79


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