Glucocorticoids and foetal heart maturation; implications for prematurity and foetal programming

Rog-Zielinska, Eva A; Richardson, Rachel; Denvir, Martin A.; Chapman, Karen

doi:10.1530/jme-13-0204

Cited by 82 publications

(78 citation statements)

References 117 publications

(141 reference statements)

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“…Glucocorticoids rise dramatically shortly before birth and are known to promote the maturation of the lung and other organs to prepare the fetus for post-natal life but their direct actions on the fetal heart are poorly understood (75, 76). Clinically, this is an important question because glucocorticoids are routinely used for improving neonatal survival of preterm babies and fetuses at risk of premature birth and excessive fetal exposure to glucocorticoids can negatively impact adult cardiovascular health (35, 77–79).…”

Section: 0 Transgenic Mouse Models Targeting Cardiomyocyte Grmentioning

confidence: 99%

Glucocorticoid signaling in the heart: A cardiomyocyte perspective

Oakley

Cidlowski

2015

The Journal of Steroid Biochemistry and Molecular Biology

104

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Heart failure is one of the leading causes of death in the Western world. Glucocorticoids are primary stress hormones that regulate a vast array of biological processes, and synthetic derivatives of these steroids have been mainstays in the clinic for the last half century. Abnormal levels of glucocorticoids are known to negatively impact the cardiovascular system; however, surprisingly little is known about the direct role of glucocorticoid signaling in the heart. The actions of glucocorticoids are mediated classically by the glucocorticoid receptor (GR). In certain cells, such as cardiomyocytes, glucocorticoid occupancy and activation of the mineralocorticoid receptor (MR) may also contribute to the observed response. Recently, there has been a surge of reports investigating the in vivo function of glucocorticoid signaling in the heart using transgenic mice that specifically target GR or MR in cardiomyocytes. Results from these studies suggest that GR signaling in cardiomyocytes is critical for the normal development and function of the heart. In contrast, MR signaling in cardiomyocytes participates in the development and progression of cardiac disease. In the following review, we discuss these genetic mouse models and the new insights they are providing into the direct role cardiomyocyte glucocorticoid signaling plays in heart physiology and pathophysiology.

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Section: 0 Transgenic Mouse Models Targeting Cardiomyocyte Grmentioning

confidence: 99%

Glucocorticoid signaling in the heart: A cardiomyocyte perspective

Oakley

Cidlowski

2015

The Journal of Steroid Biochemistry and Molecular Biology

104

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“…This onset coincides with the Gc surge which occurs at ~ E14.5 in mice, towards the end of the pseudoglandular stage. In humans, the Gc surge occurs just before birth (Rog-Zielinska et al 2014). GR activity in the mesenchymal compartment of the lung is currently thought to drive the correct development of the lung.…”

Section: The Role Of the Gr In Lung Developmentmentioning

confidence: 99%

“…While pre-term Gc administration is undoubtedly lifesaving, accumulated evidence suggests that it is not without consequences. For example, excess Gc exposure has longer term effects on neurodevelopment (Waffarn & Davis 2012) and cardiovascular development (Rog-Zielinska et al 2014).…”

Section: Gc Therapy and The Lungmentioning

confidence: 99%

Glucocorticoid receptors in lung cancer: new perspectives

Taylor

Ray

Sommer

2016

Journal of Endocrinology

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Proper expression of the glucocorticoid receptor (GR) plays an essential role in the development of the lung. GR expression and signalling in the lung is manipulated by administration of synthetic glucocorticoids (Gcs) for the treatment of neonatal, childhood and adult lung diseases. In lung cancers, Gcs are also commonly used as co-treatment during chemotherapy. This review summarises the effect of Gc monotherapy and co-therapy on lung cancers in vitro, in mouse models of lung cancer, in xenograft, ex vivo and in vivo. The disparity between the effects of pre-clinical and in vivo Gc therapy is commented on in light of the recent discovery of GR as a novel tumour suppressor gene.

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“…It is unlikely that the noncompaction in this case is related to corticosteroid deficiency because noncompaction of the myocardium is seen in the first four weeks of fetal life whereas the action of the glucocorticoid hormone is exhibited late in pregnancy preparing the fetus for life after birth. Glucocorticoids rise dramatically shortly before birth to help in maturation of fetal tissues and organs [6]. The fetal adrenal gland initiates de novo glucocorticoid synthesis during the second half of gestation at around 28 th week of pregnancy.…”

Section: Discussionmentioning

confidence: 99%

A case of reversible cardiomyopathy & left ventricular noncompaction

Amira¹,

Abdelbasit²,

Seidahmed³

et al. 2016

J Integr Cardiol

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This is a report of a female newborn baby who presented at the age of one hour after birth with signs of respiratory distress with marked cyanosis. The critical condition of the baby and the stormy course of the disorder highlighted the importance of starting immediate management and establishing an etiological diagnosis, as this will make the difference in the outcome and the prognosis. Clinical presentationThis was a female infant born at term after an uneventful pregnancy. Antenatal ultrasound did not show fetal anomaly and antenatal serology for infectious diseases was not significant. High vaginal swab from the mother was negative for group B streptococcus. Delivery was by elective Caesarean section because of previous section. Apgar Score was 9 and 10 at 1 and 5 minutes respectively. Birth weight was 2230 grams but the baby was vigorous with an oxygen saturation of 95% in room air at 15 minutes and was eventually sent to the normal newborn nursery.At the age of one hour the pediatric doctor was called because the baby was showing signs of respiratory distress with marked cyanosis and an oxygen saturation ranging from 70% to 80% in room air. Clinical examination revealed no signs of dysmorphism but the baby was showing respiratory distress with marked cyanosis. There were no abnormal findings on examination of the cardiovascular system. On admission to the neonatal intensive care unit (NICU) the baby was started on nasal continuous positive airway pressure (nCPAP) of 6 cm H 2 O, FiO 2 of 0.3 but the oxygen saturation (SaO 2 ) remained unchanged at 80% and below. Blood gases at that time showed a pH of 7.12, pCO 2 of 45 mm Hg and a bicarbonate of 14 mmol/I with a base deficit of -13. With the increasing requirements of oxygen the baby was shifted from nCPAP to mechanical ventilation. In spite of reaching an inspiratory pressure of 26 cm H 2 O the baby remained hypoxemic at which point a diagnosis of persistent pulmonary hypertension (PPHN) was entertained and high frequency oscillatory ventilation (HFOV) was started together with inhaled nitric oxide. Soon after admission the baby was noticed to have systemic hypotension requiring inotropic therapy. Dopamine and dobutamine were titrated to a maximum of 20 micrograms per kilogram per minute after which epinephrine and hydrocortisone were instituted consecutively because of persistent hypotension. At this point the differential diagnosis rested between cyanotic congenital heart disease, septic shock or metabolic disorder and antibiotics were started.On interviewing the family it was revealed that the parents were first-degree cousins with five living children but one of the siblings who was a male infant expired at the age of two days and the death was attributed to possible hypoxic ischemic encephalopathy, septic shock or a metabolic disorder most likely adrenal insufficiency.Taking into account the clinical presentation and the family history the baby was investigated accordingly. A chest radiograph revealed normal lung fields with no cardiomegaly. I...

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Glucocorticoids and foetal heart maturation; implications for prematurity and foetal programming

Cited by 82 publications

References 117 publications

Glucocorticoid signaling in the heart: A cardiomyocyte perspective

Glucocorticoid signaling in the heart: A cardiomyocyte perspective

Glucocorticoid receptors in lung cancer: new perspectives

A case of reversible cardiomyopathy & left ventricular noncompaction

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