Regulation of β1-adrenoceptors by glucocorticoids and thyroid hormones in fetal sheep

Tseng, Yi‐Tang; Tucker, Mark A.; Kashiwai, Kent; Waschek, James A.; Padbury, Jamés F.

doi:10.1016/0922-4106(95)90113-2

Cited by 24 publications

(13 citation statements)

References 32 publications

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“…Interestingly, there is a low level of TR occupancy in rats until the second postnatal week (46). Whereas the ␤1AR is expressed and coupled to important physiologic responses, thyroid hormone alone or in combination with corticosteroids does not increase ␤1AR receptor expression or density during fetal or early postnatal development (17,33,34). This is in contrast to studies in older animals and humans where thyroid hormones have clearly been shown to increase ␤1AR expression (28).…”

Section: Discussionmentioning

confidence: 81%

“…Studies from our group and others have shown that the ␤1AR is expressed during late fetal development in both rodents and sheep and coupled to important physiologic responses (11)(12)(13)(14)(15)(16)(17)(18). Interestingly, thyroid hormone alone or in combination with corticosteroids does not further increase ␤1AR receptor expression or density during fetal or early postnatal development (17,18,33,34). This is in marked contrast to the studies in older animals and humans where thyroid hormones have clearly been shown to increase ␤1AR expression and the increase has been shown to be at the level of gene transcription (28).…”

mentioning

confidence: 98%

“…We are interested in the hormonal regulation of the ␤1 adrenergic receptor (␤1AR) during development (11)(12)(13)(14)(15)(16)(17)(18). The ␤1AR is a member of the seven transmembrane domain, G-protein coupled receptor superfamily (19).…”

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confidence: 99%

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Liganded and Unliganded Steroid Receptor Modulation of Beta 1 Adrenergic Receptor Gene Transcription

et al. 2001

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The classical model of gene regulation by hormones involves a hormone-bound receptor interacting with a DNA response element to increase or decrease gene transcription. Steroid hormone regulation more commonly involves atypical cis-elements, co-receptors, accessory proteins, and unique modes of interaction on different genes. The thyroid hormone and retinoic acid receptors belong to the super family of steroid nuclear receptors and may modify gene expression even in the absence of ligand binding. In these studies, we characterized thyroid receptor-and retinoic acid receptor-mediated regulation of ␤1 adrenergic receptor (␤1AR) gene expression. Using cloned fragments of the ovine ␤1AR in a luciferase reporter vector, we examined the effects of thyroid receptor and retinoic acid receptor, alone and in combination with T3 or retinoic acid on ␤1AR expression. We examined expression in SK-N-SH neuroblastoma cells, CV-1 fibroblasts, and, in neonatal rat, primary cardiomyocytes. We demonstrated that even in the absence of ligand binding, thyroid receptor and retinoic acid receptor can significantly increase ␤1AR transcription activity. This effect is important in the developmental transition in ␤1AR expression during fetal and postnatal life. The classical model of gene regulation by hormones involves a hormone-bound receptor interacting with a DNA response element to increase or decrease gene transcription (1, 2). It is now appreciated that this model of hormonal regulation of gene expression is simplistic and may be the exception rather than the rule. For instance, classical models cannot explain the hormonal regulation of genes that lack canonical consensus DNA elements. These models also do not account for changes in hormonal regulation of gene expression at different developmental stages, differential regulation in different tissues, and other complexities of hormonal regulation. Steroid hormone regulation more commonly involves atypical cis-elements, co-receptors, accessory proteins, and unique modes of interaction on different genes (3).The TR and RAR belong to the super family of steroid nuclear receptors (1-4). TR and RAR bind to DNA as heterodimers with RXR (4). There is also a family of coregulators that positively and negatively regulate transcriptional activation from a variety of cis-elements in specific genes. Recently, it has been recognized that modulation of gene expression by steroid nuclear receptors may be independent of ligand binding to the steroid receptor. TR can bind to DNA in the absence of its ligand (thyroid hormone) and can regulate transcription both positively and negatively from a variety of promoters (5-7). Transactivation by TR in the absence of hormone can require cell-specific factors but may occur even with promoters that do not contain clearly defined TRE (8, 9). Similar observations have been reported for RAR (10). A precise physiologic context for nonligand-dependent regulation of transcription by these receptors has not been shown.We are interested in the hormonal regulation of ...

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Section: Discussionmentioning

confidence: 81%

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Liganded and Unliganded Steroid Receptor Modulation of Beta 1 Adrenergic Receptor Gene Transcription

et al. 2001

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“…Thus, the differences observed could reflect a cell-specific difference in the ontogeny of steroid receptor function. Another possibility is that there are specific repressor mechanisms that prevent activation of steroid receptors (Tseng et al, 1995) or inhibit signal transduction in some cell populations after activation of steroid receptors.…”

Section: Discussionmentioning

confidence: 99%

Effect of Dexamethasone Treatment on Maturational Changes in the NMDA Receptor in Sheep Brain

et al. 2000

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The objective of the present study was to examine the effect of antenatal or postnatal treatment with corticosteroids on the NMDA receptor, one of the mediators of both normal brain development and hypoxic-ischemic injury, by determining the characteristics of the receptor MK-801 binding site in untreated and corticosteroid-treated fetal and newborn lambs.3 H-MK-801 binding was performed in cerebral cortical cell membranes from fetal sheep at 88, 120, and 136 d gestation (term ϭ 150 d), and from 5-d-old lambs and adult ewes. Animals were randomized to receive dexamethasone [fetuses: 6 mg, i.m. every 12 hr for four doses to mother; lambs: 0.01 mg/kg (low dose) or 0.25 mg/kg (high dose) every 12 hr for four doses] or placebo. During development, B max (apparent number of receptors) increased, reaching a maximum in 5-d-old lambs ( p Ͻ 0.05) and decreasing in the adult brain. K d (dissociation constant) did not change, suggesting that receptor affinity was not altered during maturation. Dexamethasone treatment had no effect on MK-801 binding in the fetus or adult, but in lambs was associated with a significant decrease in B max from 2.17 Ϯ 0.18 pmol/mg protein in placebotreated animals to 1.65 Ϯ 0.8 and 1.62 Ϯ 0.07 pmol/mg protein in low-dose and high-dose animals, respectively. Affinity for 3 H-MK-801 decreased 20% after dexamethasone treatment in lambs only ( p Ͻ 0.05). Thus, dexamethasone treatment appears to modify the NMDA receptor only during a specific period of brain development.

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“…One proposed mechanism is facilitation of catecholamine effect at the cellular level through regulation of adrenergic receptors (31). However, Tseng et al (32) were not able to demonstrate increased myocardial ␤-receptor density, response, or gene expression after antenatal betamethasone treatment in the preterm fetal sheep. Despite this failure to up-regulate adrenergic receptors, this group documented improved blood pressure and cardiac output in the immediate postnatal period in betamethasone-treated lambs (33).…”

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Impaired Urinary Cortisol Excretion and Early Cardiopulmonary Dysfunction in Immature Baboons

et al. 2002

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Early adrenal insufficiency is associated with cardiopulmonary dysfunction in immature infants. Isolated cortisol levels and ACTH stimulation testing may not adequately show ontogeny of postnatal cortisol secretion nor identify at risk infants. Our objectives were 1) to determine postnatal urinary cortisol excretion rate (UCER) from birth to 14 d in immature baboons and 2) to evaluate the relation between UCER and cardiac performance. UCER was assessed via 6-h blocked urine collections from birth to 336 h of age in twenty-one 125-d gestation (term ϭ 185 d) baboons. Urinary cortisol was measured by RIA. Cardiopulmonary parameters were averaged over the same time periods as urine collection. Serial two-dimensional echocardiograms were performed. After 24-h age, a subgroup (n ϭ 8) received up to four doses (0.5-1.0 mg/kg each) of hydrocortisone for refractory hypotension. UCER significantly increased from 0 to 6 h through 66 to 72 h age for non-cortisol-treated infants. Significantly reduced UCER patterns between birth and 24 h were found for animals subsequently requiring cortisol treatment. Cortisoltreated infants had lower mean blood pressure, worse metabolic acidosis, increased fluid needs, and impaired left ventricular function between 12 and 48 h of age. No group differences were found in gas exchange or ventilator support. We conclude that adrenal cortisol secretion significantly improves over the initial Over the past decade, several reports have suggested an inadequate response of the hypothalamic-pituitary-adrenal axis in sick immature infants (1-5). This impaired adrenal function has been associated with hypotension refractory to volume and inotropic therapy, but responsive to glucocorticoid therapy (6, 7). Evidence of early adrenal insufficiency in extremely low birth weight infants has also been associated with increased risk for subsequent diagnosis of neonatal chronic lung disease (5, 7-9). In a pilot study of early hydrocortisone replacement therapy, Watterberg and colleagues (10) found improved survival without chronic lung disease among a group of high-risk immature infants.The majority of studies evaluating adrenal function in premature humans have measured serum cortisol levels at isolated points in time or after ACTH stimulation. These studies have not attempted to define the ontogeny of cortisol release over the initial hours and days of life in very immature infants. Nor have studies reported on indices of cardiac function, other than blood pressure, related to periods of suggested adrenal insufficiency or subsequent therapy.

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Regulation of β1-adrenoceptors by glucocorticoids and thyroid hormones in fetal sheep

Cited by 24 publications

References 32 publications

Liganded and Unliganded Steroid Receptor Modulation of Beta 1 Adrenergic Receptor Gene Transcription

Liganded and Unliganded Steroid Receptor Modulation of Beta 1 Adrenergic Receptor Gene Transcription

Effect of Dexamethasone Treatment on Maturational Changes in the NMDA Receptor in Sheep Brain

Impaired Urinary Cortisol Excretion and Early Cardiopulmonary Dysfunction in Immature Baboons

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