Effect of Thyroid Status on Lung and Heart Beta-Adrenergic Receptors in Fetal and Newborn Sheep

Padbury, Jamés F.; Klein, Alan H.; Polk, Daniel H.; Lam, Robert W.; Hobel, Calvin J.; Fisher, Delbert A.

doi:10.1159/000457075

Cited by 28 publications

(15 citation statements)

References 19 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: 88%

“…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).…”

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confidence: 88%

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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: 88%

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confidence: 88%

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

et al. 2001

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“…These responses may therefore be enhanced by b 3 -adrenergic agonist treatment, at least 24 h after birth. Failure to observe any additional effect of b 3 -adrenergic agonist on the postfeeding rise in colonic temperature before 12 h is likely to be linked to the rapid increase in sympathetic stimulation associated with parturition (Eliot et al 1981) and the concomitant rise in b-receptor abundance (Padbury et al 1986). …”

Section: Figurementioning

confidence: 99%

Effect of Postnatal Age and a β₃‐Adrenergic Agonist (Zeneca D7114) Administration on Uncoupling Protein‐1 Abundance in the Lamb

Bird

Mostyn

Clarke

et al. 2001

Experimental Physiology

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We examined the effect of time after birth and b 3 -adrenergic agonist (Zeneca D7114) administration on uncoupling protein-1 (UCP1) abundance and thermoregulation in the lamb. Forty twin lambs, all born normally at term, were maintained at a cold ambient temperature of between 3 and 8°C. At 0.5, 1.75, 5.25, 11.25 and 23.25 h after birth eight sets of twins were fed 20 ml of formula milk ± 10 mg kg _1 of b 3 -adrenergic agonist, and 45 min after feeding brown adipose tissue (BAT) was sampled. Colonic temperature was measured and BAT analysed for UCP1 abundance, GDPbinding to mitochondrial protein (i.e. thermogenic activity) and catecholamine content. Colonic temperature declined between 1.25 and 6 h from 40.2°C to 39.2°C and then increased to 39.8°C at 12 h, but increased after feeding at all ages. UCP1 abundance increased from 1.25 h after birth, to peak at 2 h after birth in controls, compared with 6 h after birth in

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“…Methimazole-treated CR lambs did not exhibit an age-related decline in heart rate despite heat production (per kilogram body weight) decreasing with age. These differences may be linked to changes in the ontogeny of cardiac ,J-adrenergic receptors, for which T3 is necessary to maintain a high binding capacity (Padbury, Klein, Polk, Lam, Hobel & Fisher, 1986). In addition, metabolic demands on the heart are much greater in CR lambs and this additional work could have a direct effect on hypertrophy of cardiac muscle (Cotterell & Dauncey, 1991) as well as the distribution of cardiac output (Weiss & Tse, 1995).…”

Section: Thyroid Hormones and Thermoregulationmentioning

confidence: 99%

Effect of rearing temperature on perirenal adipose tissue development and thermoregulation following methimazole treatment of postnatal lambs

Symonds¹,

Andrews²,

Buss³

et al. 1996

Experimental Physiology

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SUMMARYThis study examined the effect of ambient temperature on perirenal adipose tissue development and thermoregulation over the first month of postnatal life in lambs treated with a drug that reduces thyroid hormone synthesis (methimazole; at a dose of 50 mg day-' (kg body weight)-').Twin lambs were hand-reared at a fixed level of nutrition in either a warm (WR; 25 'C) or cool (CR; 10-15 'C) ambient temperature. Oxygen consumption, heart rate and colonic temperature were measured during non-rapid eye movement sleep in different ambient temperatures (6, 15, 25 and 34-36°C) at 7, 14 and 28 days of age. Plasma thyroid hormone concentrations decreased with postnatal age and were higher in CR than in WR lambs. All lambs increased plasma thyroid hormone concentrations and 02 consumption during cold exposure but this was not associated with a mean increase in colonic temperature in WR lambs at 7 or 28 days. Colonic temperature increased with the onset of panting at all ages when lambs were exposed to 34-36 'C, a response that was greatest at 28 days in CR lambs. An increase in colonic temperature with age was observed in CR but not WR lambs. Heart rate declined with age only in the WR group. At 8 and 29 days there were no significant differences between WR and CR groups in the occurrence of shivering or in the thermogenic activity (i.e. GDP binding to mitochondria) of perirenal adipose tissue. At 29 days WR lambs possessed more adipose tissue with a higher lipid and DNA content. It is concluded that modest changes in rearing temperature can have a large influence on the control of body temperature and thyroid hormone response to methimazole treatment. CR lambs are able to maintain higher plasma thyroid hormone concentrations and exhibit improved thermoregulation compared with WR lambs without any detectable differences in brown adipose tissue function.

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Effect of Thyroid Status on Lung and Heart Beta-Adrenergic Receptors in Fetal and Newborn Sheep

Cited by 28 publications

References 19 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 Postnatal Age and a β₃‐Adrenergic Agonist (Zeneca D7114) Administration on Uncoupling Protein‐1 Abundance in the Lamb

Effect of rearing temperature on perirenal adipose tissue development and thermoregulation following methimazole treatment of postnatal lambs

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Effect of Thyroid Status on Lung and Heart Beta-Adrenergic Receptors in Fetal and Newborn Sheep

Cited by 28 publications

References 19 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 Postnatal Age and a β3‐Adrenergic Agonist (Zeneca D7114) Administration on Uncoupling Protein‐1 Abundance in the Lamb

Effect of rearing temperature on perirenal adipose tissue development and thermoregulation following methimazole treatment of postnatal lambs

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Effect of Postnatal Age and a β₃‐Adrenergic Agonist (Zeneca D7114) Administration on Uncoupling Protein‐1 Abundance in the Lamb