CELLULAR UPTAKE OF THYROID HORMONE BY HUMAN HEPATOCYTES
CELLULAR UPTAKE OF THYROID HORMONE BY HUMAN HEPATOCYTES
批准号:
3463406
负责人:
DAVID H SARNE
金额:
$9.27万
依托单位国家:
美国
项目类别:
财政年份:
1987
资助国家:
美国
项目状态:
已结题
起止时间:
1987-08-07 至 1991-07-31
关键词:
adenosine triphosphate albumins amiodarone free fatty acids furosemide hormone binding protein hormone receptor human tissue hyperthyroidism hypothyroidism liver cells liver metabolism membrane permeability neoplastic cell culture for noncancer research peptide hormone metabolism pinocytosis propranolol thyroid hormone binding protein thyroid hormones thyroxine triiodothyronine
中文摘要
甲状腺激素(TH)进入细胞是至关重要的,但是
英文摘要
The entry of thyroid hormone (TH) into cells is a critical, but
poorly understood process. Alterations of TH entry into cells may
contribute to changes in thyroid hormone metabolism during
fasting, in severely ill patients (NTI), in hypothyroidism, and as a
consequence of drugs. Altered entry of TH into cells has been
described in patients with abnormal TH serum binding proteins
and as a primary inherited defect producing generalized
resistance to TH. The long term goal of these studies is to
delineate the mechanisms and regulation of the entry of thyroid
hormone into human cells and to evaluate its contributions to
clinical problems. Cultured human hepatocytes, Hep G2, will be
utilized as they retain many properties of normal human liver
cells and allow experimental conditions to be controlled.
Incubation of these cells with radioiodine labeled T3 and T4 with
unlabeled TH and inactive metabolites will establish if human
liver cells have saturable uptake systems for TH that are
functional at physiologic concentrations, and specific for active
TH. Incubation with varying concentrations of free T3 and T4 and
purified albumin, thyroxine binding prealbumin (TBPA), and
thyroxine binding globulin (TBG) will indicate if these proteins
facilitate uptake of TH. Incubation of cells with radioiodine
labeled albumin, TBPA, and TBG will determine whether these
serum proteins are specifically bound to human liver cells.
Uptake of tracer TH from serum of subjects with abnormal serum
TH binding proteins will evaluate whether these proteins alter the
cellular uptake. Incubation of TH with furosemide and free fatty
acids will determine whether these postulated inhibitors of TH
binding to serum proteins in NTI also interfere with cellular entry
of TH. Treatment of Hep G2 cells with drugs which block cellular
ATP generation will indicate whether the uptake of thyroid
hormone into human cells is energy dependent. Pre-treatment
with drugs which inhibit endocytosis will indicate whether this
process is important in the uptake of TH by human cells.
Membrane preparations obtained from the Hep G2 cells will be
combined with varying concentrations of labeled and unlabeled T3
and T4 to detect specific membrane receptors. Incubation of
labeled TH with ipodate, amiodarone and propranolol will evaluate
if they alter cellular entry of TH by competing for uptake,
inhibiting deiodination, or decreasing cellular ATP content. The
effect of long term treatment of Hep G2 cells with hypothyroid
serum and serum with excess TH will establish whether thyroid
hormone status may alter the entry of TH into human cells.
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Sequencing of the variant thyroxine-binding globulin (TBG)-San Diego reveals two nucleotide substitutions.
对变体甲状腺素结合球蛋白(TBG)-圣地亚哥的测序揭示了两个核苷酸取代。
DOI:
10.1016/0925-4439(92)90105-v
发表时间:
1992
期刊:
Biochimica et biophysica acta
影响因子:
--
作者:
[Bertenshaw,R, Sarne,D, Tornari,J, Weinberg,M, Refetoff,S]
通讯作者:
Refetoff,S
Serum thyrotropin and prolactin in the syndrome of generalized resistance to thyroid hormone: responses to thyrotropin-releasing hormone stimulation and short term triiodothyronine suppression.
甲状腺激素普遍抵抗综合征中的血清促甲状腺素和催乳素:对促甲状腺素释放激素刺激和短期三碘甲状腺原氨酸抑制的反应。
DOI:
10.1210/jcem-70-5-1305
发表时间:
1990
期刊:
The Journal of clinical endocrinology and metabolism
影响因子:
--
作者:
[Sarne,DH, Sobieszczyk,S, Ain,KB, Refetoff,S]
通讯作者:
Refetoff,S
Limitations to the use of a sensitive assay for serum thyrotropin in the assessment of thyroid status.
在评估甲状腺状态时使用血清促甲状腺素敏感测定法的局限性。
DOI:
--
发表时间:
1989
期刊:
Archives of internal medicine
影响因子:
--
作者:
[Ehrmann,DA, Weinberg,M, Sarne,DH]
通讯作者:
Sarne,DH
A new inherited abnormality of thyroxine-binding globulin (TBG-San Diego) with decreased affinity for thyroxine and triiodothyronine.
甲状腺素结合球蛋白(TBG-圣地亚哥)的一种新遗传异常,与甲状腺素和三碘甲状腺原氨酸的亲和力降低。
DOI:
10.1210/jcem-68-1-114
发表时间:
1989
期刊:
The Journal of clinical endocrinology and metabolism
影响因子:
--
作者:
[Sarne,DH, Refetoff,S, Nelson,JC, Linarelli,LG]
通讯作者:
Linarelli,LG
Normal cellular uptake of thyroxine from serum of patients with familial dysalbuminemic hyperthyroxinemia or elevated thyroxine-binding globulin.
家族性白蛋白异常性高甲状腺素血症或甲状腺素结合球蛋白升高患者血清中甲状腺素的正常细胞摄取。
DOI:
10.1210/jcem-67-6-1166
发表时间:
1988
期刊:
The Journal of clinical endocrinology and metabolism
影响因子:
--
作者:
[Sarne,DH, Refetoff,S]
通讯作者:
Refetoff,S
THYROID HORMONE EFFECTS ON BONE AND THYROID DISORDERS
-
批准号:2144340
-
项目类别:
-
资助金额:$22.98万
-
财政年份:1995
-
负责人:DAVID H SARNE
-
依托单位:
THYROID HORMONE EFFECTS ON BONE AND THYROID DISORDERS
-
批准号:2668306
-
项目类别:
-
资助金额:$24.33万
-
财政年份:1995
-
负责人:DAVID H SARNE
-
依托单位:
THYROID HORMONE EFFECTS ON BONE AND THYROID DISORDERS
-
批准号:2144339
-
项目类别:
-
资助金额:$17.23万
-
财政年份:1995
-
负责人:DAVID H SARNE
-
依托单位:
THYROID HORMONE EFFECTS ON BONE AND THYROID DISORDERS
-
批准号:2377795
-
项目类别:
-
资助金额:$23.39万
-
财政年份:1995
-
负责人:DAVID H SARNE
-
依托单位:
CELLULAR UPTAKE OF THYROID HORMONE BY HUMAN HEPATOCYTES
-
批准号:3463405
-
项目类别:
-
资助金额:$9.3万
-
财政年份:1987
-
负责人:DAVID H SARNE
-
依托单位:
CELLULAR UPTAKE OF THYROID HORMONE BY HUMAN HEPATOCYTES
-
批准号:3463404
-
项目类别:
-
资助金额:$10.25万
-
财政年份:1987
-
负责人:DAVID H SARNE
-
依托单位:
海外基金