Respiratory disease in very-low-birthweight infants after prenatal thyrotropin-releasing hormone and glucocorticoid

Ballard, Roberta A.; Ballard, Philip L.; Bracken, Michael B.; Moya, Fernando; Gross, Ian; Creasy, Kate Townsend; Padbury, Jamés F.; Polk, Daniel H.

doi:10.1016/0140-6736(92)90337-3

Cited by 121 publications

(24 citation statements)

References 22 publications

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“…Unfortunately, there are, to date, no data regarding hormonal regulation of the AOE system in human lung. Clinical trials with combined TRH and glucocorticoid treatment have shown a lesser incidence of bronchopulmonary dysplasia in very-low-birth-weight infants but surprisingly no significant decrease in the incidence or severity of respiratory distress syndrome (24). The reported decrease in bronchopulmonary dysplasia (18 verslls 44% in untreated infants) in these premature infants treated with high fractional inspired O2 levels would seem to represent an apparent disparity with our experimental findings of decreased AOE defenses due to similar combined hormonal treatment.…”

Section: Discussioncontrasting

confidence: 74%

“…However, because the human placenta is rather impermeable to thyroid hormone. thyroidreleasing hormone or TRH (which does cross the placenta) is the agent that combined with long-acting synthetic glucocorticoid hormone (betamethasone) is being used in incipient premature delivery situations (23,24). Experimentally, TRH also appears to act in an additive or synergistic fashion with glucocorticoid in stimulating earlier lung surfactant system maturation (25,26).…”

Section: Discussionmentioning

confidence: 99%

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Negative Regulation of Antioxidant Enzyme Gene Expression in the Developing Fetal Rat Lung by Prenatal Hormonal Treatments

1993

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administration of thyrotropin-releasing hormone (TRH) or T R H plus dexamethasone (DEX) to pregnant rats accelerates lung surfactant system development in late gestation, but paradoxically depresses the normal late gestational elevation in fetal lung antioxidant enzyme (AOE) activities (Pediatr Res 30522, 1991). In these present studies, we tested whether both prenatal hormonal treatments act to depress normal fetal lung AOE development by negative regulation of AOE gene expression. We used solution hybridization to quantitate the concentration of AOE mRNA. Results of the developmental studies revealed significantly decreased lung mRNA concentrations of copper-zinc superoxide dismutase, manganese superoxide dismutase, catalase, and glutathione peroxidase in late gestation a s a result of prenatal TRH treatment. The addition of DEX administration did not reverse the lowered expression of lung AOE genes due to T R H treatment, but instead resulted in significant additional decreases in pulmonary AOE mRNA levels a t both 21 and 22 d of gestation.The tested AOE mRNA half-lives (stabilities) revealed no significant differences between controls (8.0-10.5 h) and TRH-treated (8.2-9.5 h) and TRH-plus-DEX treatment (7.8-10.7 h) groups. These findings suggest that prenatal treatment with T R H and with T R H plus DEX acts to depress the normal late fetal lung AOE activity elevations by (direct) negative regulation of AOE gene expression, and the decreased AOE expression is likely regulated at the level of gene transcription rather than posttranscriptionally. (Pediatr Res 33: 171-176, 1993) Abbreviations AOE, antioxidant enzyme CuZnSOD, copper-zinc superoxide dismutase SOD, superoxide dismutase MnSOD, manganese superoxide dismutase CAT, catalase GP, glutathione peroxidase TRH, thyrotropin-releasing hormone T3, triiodothyronine DEX, dexamethasone cRNA, complementary RNA 2). It has been demonstrated in each of the five different species examined to date-the rat, rabbit, guinea pig, hamster. and sheep-that development of the surfactant system and the lung AOE system share a chronologically similar late gestational pattern of development, and that the developing lung markedly increases both its surfactant content and its AOE activity levels during the final I0 to 15% of gestation (3-6). The late gestational rise in AOE (SOD. CAT. and GP) activities is considered to be a normal "preparation for birth" phenomenon that is required to assure safe respiratory functioning of the newborn's lung when it is suddenly exposed to several-fold-higher O2 tension immediately after birth than the O2 tension experienced in We have previously demonstrated that. although prenatal administration of either T3 or T, plus DEX to pregnant rats accelerated surfactant system development in the late fetal lung, both of these hormonal treatments significantly delayed or decreased pulmonary AOE system development (8). Further studies were done recently using the same hormonal agents (TRH instead of T3) that are currently being tested clinically to try...

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Section: Discussioncontrasting

confidence: 74%

Section: Discussionmentioning

confidence: 99%

Negative Regulation of Antioxidant Enzyme Gene Expression in the Developing Fetal Rat Lung by Prenatal Hormonal Treatments

1993

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“…Teoricamente, os glicocorticóides podem afetar o curso da hipertensão em gestantes devido às suas atividades mineralocorticóides, que acarretariam elevação dos níveis pressóricos. Porém, tanto a betametasona como a dexametasona representam uma classe de fluorocorticóides com ação mineralocorticóide mínima ou ausente 7 , praticamente sem nenhum impacto em termos de expansão volumétrica, ambos com atividade biológica similar, atravessando a barreira placentária e atingindo níveis adequados no compartimento fetal para sua ação farmacológica. As doses preconizadas são sintetizadas no quadro1.…”

Section: Discussionunclassified

Corticoterapia pré-natal nas síndromes hipertensivas da gestação e seus efeitos na pressão arterial materna

Sass¹,

Cançado²,

Oliveira³

et al. 2001

Rev. Assoc. Med. Bras.

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RESUMO OBJETIVOS. Avaliar o comportamento da pressão arterial em gestantes portadoras de síndromes hipertensivas na vigência de ciclo de corticóide (esquema de LIGGINS) utilizado para a aceleração da maturidade pulmonar fetal.MÉTODOS. A partir de estudo retrospectivo, foram avaliadas 27 gestantes portadoras de hipertensão arterial, com idade gestacional entre 24 e 34 semanas, submetidas a corticoterapia antenatal. Para tanto, foi realizada análise estatística das médias das pressões arteriais sistólicas e diastólicas separadamente, dos dias anterior, primeiro e segundo dias que compõem o ciclo de corticoterapia e do dia posterior a este ciclo. Obtidas as variâncias, foi aplicado o teste F Statistic, analisado através do valor de p, significante, se menor que 0,05.RESULTADOS. Não foi observada variação significativa dos níveis de pressão arterial, seja sistólica como diastólica, não se identificando dificuldades no controle clínico das pacientes, não tendo sido observada necessidade de elevação das doses de drogas hipotensores utilizadas.CONCLUSÃO. Nossos resultados observaram segurança na utilização de ciclos de corticóides em pacientes portadoras de hipertensão arterial em relação à possíveis agravos dos níveis pressóricos.UNITERMOS: Hipertensão arterial na gestação. Prematuridade. Corticoterapia pré-natal. *Correspondência:Nelson Sass Rua Umberto Boccioni, 210 -Cep: 02441-150Fax: 6231-9969 São Paulo -SP -E-mail: nelsonsa.alp@zaz.com.br INTRODUÇÃONo início da década de 70, a administração de corticóides em experimentação animal refletiu em uma ação efetiva na aceleração da capacidade funcional de pulmões de recém-nascidos prematuros 1 , reduzindo de maneira significativa a incidência da síndrome do desconforto respiratório, com redução evidente nas taxas de mortalidade neo-natal.Seguindo-se a divulgação destes resultados, vários trabalhos foram desenvolvidos onde se procurava estabelecer de maneira definitiva sua ação benéfica e possíveis reações adversas, possibilitando estender seu uso na rotina diária de assistência ao parto prematuro. Baseada nas melhores evidên-cias, acumuladas na experiência anterior de vários trabalhos 2 , sua utilização passa a ser recomendada pelo Instituto de Saúde dos Estados Unidos em consenso estabelecido por equipe multidisciplinar como norma na assistência à prematuridade 3 .Ressalte-se ainda as conseqüências do ponto de vista econômico que esta terapêutica pôde acarretar. Os custos relacionados ao atendimento ao RN prematuro em unidades de terapia intensiva é extremamente elevado, somando-se ainda os gastos decorrentes das complicações tardias da prematuridade. Estima-se que nos EUA, haveria uma economia de 157 milhões de dólares a cada ano, apenas considerando a redução de tempo de permanência hospitalar em unidades de terapia intensiva.Levando-se em conta que a prematuridade representa para o Brasil problema de extrema importância, particularmente relacionada à hipertensão arterial materna, a utilização de rotina da corticoterapia pré-natal pode contribuir de forma efetiva par...

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“…This regulation is likely mediated differently for the individual AOE. ( (1)(2)(3). It has been previously demonstrated by our laboratories that although prenatal administration of TRH +DEX to pregnant rats accelerates surfactant system development in the late fetal lung, this same hormonal treatment significantly decreases the normal fetal lung AOE (SOD, CAT, and GP) activity elevations in late gestation (4).…”

mentioning

confidence: 89%

Positive Regulation of Pulmonary Antioxidant Enzyme Gene Expression by Prenatal Thyrotropin Releasing Hormone Plus Dexamethasone Treatment in Premature Rats Exposed to Hyperoxia

1995

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Prenatal administration of thyrotropin releasing hormone (TRH) plus dexamethasone (DEX) to pregnant rats produces significantly depressed fetal lung antioxidant enzyme (AOE) activities and AOE mRNA levels in late gestation. Because of this negative regulation of AOE gene expression in the late fetal lung, we hypothesized that hormonally pretreated prematurely delivered rats might demonstrate inferior tolerance to prolonged hyperoxia. Litters of prenatal TRH+DEX-treated and shamtreated prematurely delivered rat pups (gestational d 21 of 22) were randomized to either >95% O 2 or room air for up to 14 d. The right lungs of 2-and 7-d exposure pups were assayed for AOE activities; the left lungs of the same pups were used to quantitate the concentrations of AOE mRNA by solution hybridization. The prenatal TRH+ DEX-treated pups were able to induce adaptive lung AOE mRNA and activity responses to hyperoxia by 2 d of exposure; and by 7 d in O 2 they showed greater increases in AOE mRNA concentrations and AOE activities in response to hyperoxic challenge compared with the sham-treated controls. Lung lipid surfactant measurements after hyperoxia were not affected by prenatal TRH + DEX treatment. In addition, TRH + DEX-pretreated premature rats did not show the hypothesized increased susceptibility to 02-induced lung damage and lethality, but, in fact, had slightly improved hyperPrenatal hormonal therapy with maternal administration of a combination of TRH and glucocorticoids is now being extensively tested clinically in threatened premature deliveries to try to rapidly stimulate lung maturation and reduce the incidence and severity of respiratory distress syndrome in premature Received May 20, 1994; accepted December 1, 1994 oxic survival (d 3-7 of O 2 exposure) compared with shamtreated controls. Exposure to hyperoxia significantly reduced serum triiodothyronine and thyroxine levels in the sham-control pups. These findings suggest that although TRH + DEXpretreated premature rats have decreased lung AOE gene expression at the time of preterm delivery, subsequent hyperoxic exposure is able to convert AOE gene expression to positive regulation which results in more rapid and greater increases in protective AOE activity levels. This regulation is likely mediated differently for the individual AOE. (Pediatr Res 37: 611-616, 1995) Abbreviations TRH, thyrotropin releasing hormone DEX, dexamethasone AOE, antioxidant enzyme CuZnSOD, copper-zinc superoxide dismutase MnSOD, manganese superoxide dismutase CAT, catalase GP, glutathione peroxidase DSPC, disaturated phosphatidylcholine T3' triiodothyronine T 4 , thyroxine infants (1-3). It has been previously demonstrated by our laboratories that although prenatal administration of TRH +DEX to pregnant rats accelerates surfactant system development in the late fetal lung, this same hormonal treatment significantly decreases the normal fetal lung AOE (SOD, CAT, and GP) activity elevations in late gestation (4). This hormonal effect appears to depend on a pretranslational/ transcript...

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Respiratory disease in very-low-birthweight infants after prenatal thyrotropin-releasing hormone and glucocorticoid

Cited by 121 publications

References 22 publications

Negative Regulation of Antioxidant Enzyme Gene Expression in the Developing Fetal Rat Lung by Prenatal Hormonal Treatments

Negative Regulation of Antioxidant Enzyme Gene Expression in the Developing Fetal Rat Lung by Prenatal Hormonal Treatments

Corticoterapia pré-natal nas síndromes hipertensivas da gestação e seus efeitos na pressão arterial materna

Positive Regulation of Pulmonary Antioxidant Enzyme Gene Expression by Prenatal Thyrotropin Releasing Hormone Plus Dexamethasone Treatment in Premature Rats Exposed to Hyperoxia

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