Rat pancreatic nuclear thyroid hormone receptor: Characterization and postnatal development

Lee, Josephine T.; Lebenthal, Emanuel; Lee, Ping-Cheung

doi:10.1016/0016-5085(89)91635-1

Cited by 22 publications

(16 citation statements)

References 33 publications

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“…Previous studies examining glucocorticoid regulation of the rat TRH promoter demonstrated that the sequence at 200 of the rat TRH gene can bind to glucocorticoid receptors in vitro. Also, transient transfection studies in a cell line containing endogenous glucocorticoid receptors demonstrated a 4-to 6-fold stimulation by Dex (Lee et al 1989, Stevenin & Lee 1995. As expected, TRH-LUC ( 113/+84) construct lacking GRE sequence was not sensitive to the Dex effect.…”

Section: Discussionsupporting

confidence: 71%

“…The activity of the sequence also depends on the relative concentrations of other unknown transcription factors. Our results indicate that T 3 may inhibit TRH promoter activity, at least in primary islets and fibroblasts that possess T 3 receptor sites (Lee et al 1989). Our previous results already indicated changes in the steady-state concentrations of pp-TRH mRNA and TRH.…”

Section: Discussionsupporting

confidence: 68%

“…The fibroblast layer remaining on the bottom of the culture dishes was used as a primary non-islet cell (negative) control. The detached islets were cultured free-floating in 50 mm Petri dishes which did not permit cell attachment (Falcon 1007; Falcon Plastics, San Diego, CA, USA), in complete (Lee et al 1989) and a T 3 -response element half-site (TRE) (Stevenin & Lee 1995) are indicated. Promoter fragments of indicated lengths were cloned upstream of the luciferase gene in the vector pA3 LUC.…”

Section: Preparation Of Isletsmentioning

confidence: 99%

“…In contrast, the synthetic glucocorticoid, dexamethasone (Dex), up-regulates TRH mRNA and TRH of the pituitary cells in culture (Bruhn et al 1994), a thyroid cell line (Tavianini et al 1989) and in fetal islets in culture (P Fragner & S Aratan de Leon, unpublished observations). Two lines of evidence point to T 3 and Dex having a direct influence on pp-TRH gene expression; the presence of nuclear T 3 receptors in the pancreas (Lee et al 1989) and T 3 receptor binding site consensus sequences in the TRH promoter (Stevenin & Lee 1995). A glucocorticoid regulatory element (GRE) is present on the TRH gene promoter (Lee et al 1988) and the pancreatic -cells are the only islet cells bearing the glucocorticoid receptor (Fischer et al 1990, Delaunay et al 1997.…”

Section: Introductionmentioning

confidence: 99%

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Differential regulation of the TRH gene promoter by triiodothyronine and dexamethasone in pancreatic islets

Frágner¹,

Sl²,

Leon³

2001

Journal of Endocrinology

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TRH was initially found in the hypothalamus and regulates TSH secretion. TRH is also produced by insulincontaining -cells. Endogenous TRH positively regulates glucagon secretion and attenuates pancreatic exocrine secretion. We have previously shown that triiodothyronine (T 3 ) down-regulates pre-pro-TRH gene expression in vivo and in vitro. The present study was designed to determine the initial impact of T 3 on rat TRH gene promoter and to compare this effect with that of dexamethasone (Dex). Primary islet cells and neoplastic cells (HIT T-15 and RIN m5F) were transiently transfected with fragments of the 5 -flanking sequence of TRH fused to the luciferase reporter gene. The persistence of high TRH concentrations in fetal islets in culture, probably due to transactivating factors, allowed us to explore how T 3 and Dex regulate the TRH promoter activity in transfected cells and whether the hormone effect is dependent on the cell type considered. TRH gene promoter activity is inhibited by T 3 in primary but not neoplastic cells and stimulated by Dex in both primary and neoplastic cells of islets. These findings validate previous in vivo and in vitro studies and indicate the transcriptional impact of these hormones on TRH gene expression in the pancreatic islets.

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Section: Discussionsupporting

confidence: 71%

Section: Discussionsupporting

confidence: 68%

Section: Preparation Of Isletsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Differential regulation of the TRH gene promoter by triiodothyronine and dexamethasone in pancreatic islets

Frágner¹,

Sl²,

Leon³

2001

Journal of Endocrinology

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“…More importantly, we found that the precocious induction of exocrine enzymes and glucocorticoid receptors by T 4 occurred even in adrenalectomized rats and that T 4 and glucocorticoid had additive effects on adrenalectomized pups (3,5), thus suggesting a possible direct action of thyroid hormone on the exocrine pancreas. Recently we have documented the presence of T 3 nuclear receptors in the rat pancreas and that the T 3 receptor function shows a maturation profile during postnatal development (7).…”

mentioning

confidence: 99%

Thyroidal Regulation of Rat Pancreatic Nuclear Triiodothyronine Receptor during Postnatal Development

1990

Self Cite

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We have shown previously that the rat pancreas contains nuclear T3 receptors which exhibit a characteristic maturation pattern during development. To investigate whether these receptors are subjected to autologous regulation by thyroid hormones, the effect of T4 on the binding capacity (Bmax), dissociation constant (Kd), and receptor occupancy were followed in intact rat pups at various ages. Hyperthyroidism (by daily injection of T4 0.1 micrograms/g body wt to intact pups starting 4 days before death at 5, 10, 15, and 20 days of age) increased while hypothyroidism (by propylthiouracil feeding) decreased the total T3 binding capacity during preweaning ages (mean maximal binding capacities as estimated by Scatchard analysis, at 30 C for 14-20 days old eu-, hyper-, and hypothyroid pups: 186, 229, and 129 fmol/mg non-histone protein (NHP). The thyroid conditions also affected the percentage of T3 receptor occupancy but not the affinity of binding (as measured by Kd). Concomitantly, these conditions also caused corresponding changes in pancreatic weights, DNA and protein contents, and the concentrations of amylase, trypsinogen, and lipase. The postnatal developmental retardation induced by 6-n-propyl-2-thiouracil treatment was reversed by T4 replacement. The results suggest that rat pancreatic T3 nuclear receptors during postnatal ages are modulated by T4, and such modulation apparently in turn affects the development of the exocrine enzymes.

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Postnatal Maturation of the Exocrine Pancreas in Mammals

Githens

1990

J. pediatr. gastroenterol. nutr.

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Rat pancreatic nuclear thyroid hormone receptor: Characterization and postnatal development

Cited by 22 publications

References 33 publications

Differential regulation of the TRH gene promoter by triiodothyronine and dexamethasone in pancreatic islets

Differential regulation of the TRH gene promoter by triiodothyronine and dexamethasone in pancreatic islets

Thyroidal Regulation of Rat Pancreatic Nuclear Triiodothyronine Receptor during Postnatal Development

Postnatal Maturation of the Exocrine Pancreas in Mammals

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