Glucocorticoid Stimulation of Corticotropin-Releasing Hormone Gene Expression Requires a Cyclic Adenosine 3′,5′-Monophosphate Regulatory Element in Human Primary Placental Cytotrophoblast Cells*

Cheng, You; Nicholson, Richard C.; King, Bruce R.; Chan, Eng‐Cheng; Fitter, John T.; Smith, Roger

doi:10.1210/jcem.85.5.6552

Cited by 32 publications

(21 citation statements)

References 42 publications

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“…Although the CRH gene and mRNA of pCRH and hypothalamic CRH appear identical (Arbiser et al, 1988;Frim et al, 1988), their regulation is tissue specific. In contrast to the inhibitory influence of glucocorticoids on expression of the CRH gene in the hypothalamus, glucocorticoids activate the promoter region in the placenta and stimulate the synthesis of CRH (Cheng et al, 2000;Robinson et al, 1988). The difference in behavior of the CRH gene in the placenta and hypothalamus is due to the expression of different transcription factors, co-activators and corepressors in these two tissues (King et al, 2002).…”

Section: The Hpa Axis In Pregnancy and Postpartummentioning

confidence: 99%

“…The difference in behavior of the CRH gene in the placenta and hypothalamus is due to the expression of different transcription factors, co-activators and corepressors in these two tissues (King et al, 2002). In vivo and in vitro studies have documented that glucocorticoids stimulate the production of CRH mRNA and protein from placental cells in a dose-response manner (Cheng et al, 2000;Glynn et al, 2007;King et al, 2001;Sandman et al, 2006). This positive feedback loop results in dramatic elevations of maternal ACTH, cortisol and pCRH across gestation (see Fig.…”

Section: The Hpa Axis In Pregnancy and Postpartummentioning

confidence: 99%

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New insights into the role of perinatal HPA-axis dysregulation in postpartum depression

2013

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Postpartum depression affects 10-20% of women following birth and exerts persisting adverse consequences on both mother and child. An incomplete understanding of its etiology constitutes a barrier to early identification and treatment. It is likely that prenatal hormone trajectories represent both markers of risk and also causal factors in the development of postpartum depression. During pregnancy the maternal hypothalamic-pituitary-adrenal axis undergoes dramatic alterations, due in large part, to the introduction of the placenta, a transient endocrine organ of fetal origin. We suggest that prenatal placental and hypothalamic-pituitary-adrenal axis dysregulation is predictive of risk for postpartum depression. In this model the positive feedback loop involving the systems regulating the products of the HPA axis results in higher prenatal levels of cortisol and placental corticotropin-releasing hormone. Greater elevations in placental corticotropin-releasing hormone are related to a disturbance in the sensitivity of the anterior pituitary to cortisol and also perhaps to decreased central corticotropin-releasing hormone secretion. Secondary or tertiary adrenal insufficiencies of a more extreme nature, which emerge during the prenatal period, may be predictive of an extended or more pronounced postpartum hypothalamic-pituitary-adrenal refractory period, which in turn represents a risk factor for development of postpartum depression. In addition to reviewing the relevant existing literature, new data are presented in support of this model which link elevated placental corticotropin-releasing hormone with low levels of ACTH at 3-months postpartum. Future research will further elucidate the role of hypothalamic-pituitary-adrenal axis dysregulation in postpartum depression and also whether prenatal placental and hypothalamic-pituitary-adrenal profiles might prove useful in the early identification of mothers at risk for postpartum mood dysregulation.

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Section: The Hpa Axis In Pregnancy and Postpartummentioning

confidence: 99%

Section: The Hpa Axis In Pregnancy and Postpartummentioning

confidence: 99%

New insights into the role of perinatal HPA-axis dysregulation in postpartum depression

2013

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“…Glucocorticoids exert a negative feedback effect on CRH in the hypothalamus, and it has been shown that dexamethasone is able to reduce cAMP stimulation of the CRH promoter by more than 50 percent in transiently transfected AtT20 cells (47). Conversely, in the placenta glucocorticoids act to increase both basal and cAMP stimulated CRH promoter activity in transfected human primary placental cells (47).…”

Section: Role Of Glucocorticoidsmentioning

confidence: 99%

“…The glucocorticoid dependent stimulation of CRH in the placenta does not appear to involve the GR binding sites which mediate glucocorticoid repression of CRH activity in the AtT20 cells (33). A study to locate the region required for dexamethasone stimulation of CRH in the placenta, using transfections of luciferase reporter constructs containing progressive 5' deletions of the human CRH gene into cultured human primary placental cells, found that deletion of the region between -342 and -213bp resulted in loss of the dexamethasone responsiveness (47).…”

Section: Role Of Glucocorticoidsmentioning

confidence: 99%

Tissue specific epigenetic differences in CRH gene expression

Abou-Seif

Shipman²,

Allars³

et al. 2012

Front Biosci

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Corticotropin Releasing Hormone (CRH), a 41-amino acid peptide, is a major regulator of hypothalamic-pituitary-adrenal axis function. CRH also has important roles in several processes pertaining to pregnancy and parturition, including being a possible regulator of gestational length and predictor of pre-term birth. Regulation of the CRH promoter exhibits some tissue-specificities, the most well characterized example being glucocorticoids, which can stimulate placental CRH production but suppress hypothalamic CRH. In the last decade there has been growing interest in the role of epigenetic regulation of gene expression. Modification of the structure of chromatin is an example of epigenetic change affecting gene expression. We have found that inhibition of histone deacetylases results in an increase in CRH expression in the AtT20 pituitary cell line, but a decrease in CRH expression in the placenta. In this paper we review tissue specific differences in CRH gene expression, and discuss how epigenetic chromatin modification mechanisms can relate to tissue specific differences in expression of CRH.

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“…In particular, while glucocorticoids inhibit hypothalamic production of CRH, they stimulate placental production. This stimulatory effect occurs via the cyclic AMP response element in the CRH promoter (Cheng et al ., 2000). The exponential rise observed in corticotrophin‐releasing hormone during pregnancy may well be driven by a positive feed forward circuit involving glucocorticoid production (Karalis et al ., 1996).…”

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confidence: 99%