Regulation of progesterone production in human term trophoblasts in vitro by CRH, ACTH and cortisol (prednisolone)

Jeschke, Udo; Mylonas, Ioannis; Richter, Dagmar; Höcker, I; Briese, Volker; Makrigiannakis, Antonis; Friese, Klaus

doi:10.1007/s00404-005-0728-0

Cited by 20 publications

(11 citation statements)

References 37 publications

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“…It has been suggested that this CRH-regulated metabolic barrier is part of a mechanism that prevents myometrial activation (28). By contrast, findings such as CRH stimulation of placental prostaglandin production and inhibition of progesterone production from placental trophoblast (29) might indicate that the actions of CRH help the myometrial transition from relaxation to active contractions.…”

Section: Placenta and Foetal Membranesmentioning

confidence: 99%

Placental Corticotrophin‐Releasing Hormone and its Receptors in Human Pregnancy and Labour: Still a Scientific Enigma

Grammatopoulos

2008

J Neuroendocrinology

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It is now accepted that, in humans, placental corticotrophin‐releasing hormone (CRH) is involved in the mechanisms controlling the onset of labour; however, the precise biological role in foeto–maternal tissues remain enigmatic. Maternal plasma levels of CRH rise exponentially as pregnancy progresses towards term and peak during labour; however, evidence to link this with an active role in the onset and progression of labour, is still inconclusive. Certainly, one of the tissues targeted by CRH is the myometrial smooth muscle, which expresses a plethora of specific CRH receptors. This finding implicates CRH in the mechanisms preparing the myometrial microenvironment for the onset of labour and possibly in the regulation of active contractility during labour. Other gestational tissues also targeted by CRH include the placenta, foetal membranes and foetal adrenals, where CRH might regulate distinct physiological functions, ranging from control of vascular tone to adrenal steroidogenesis and prostaglandin synthesis and activity. Given the unique, among mammals, pattern of human placental CRH secretion and CRH receptor expression and signalling during pregnancy and labour, there are only limited biological tools available to delineate the actions of CRH in foeto–maternal tissues, primarily based on in vitro characterisation of the signalling and molecular events driven by CRH. This review will set in context the current concepts about the role of CRH and its receptors during pregnancy and labour, focusing on the unresolved questions and paradoxes that currently exist.

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Section: Placenta and Foetal Membranesmentioning

confidence: 99%

Placental Corticotrophin‐Releasing Hormone and its Receptors in Human Pregnancy and Labour: Still a Scientific Enigma

Grammatopoulos

2008

J Neuroendocrinology

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“…Two recent studies have demonstrated a reduction in the rate of preterm birth with intravaginal progesterone administration to women with premature cervical shortening3, 4. Progesterone is known to affect several cellular physiologies in each tissue of the reproductive tract including the cervix5–21.…”

Section: Introductionmentioning

confidence: 99%

Effect of progesterone on cervical shortening in women at risk for preterm birth: secondary analysis from a multinational, randomized, double‐blind, placebo‐controlled trial

O’Brien

DeFranco

Adair

et al. 2009

Ultrasound in Obstet & Gyne

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Objectives To determine whether progesterone supplementation alters cervical shortening in women at increased risk for preterm birth. Methods (difference 1.6 (95% CI, mm; P = 0.02, ANCOVA). In the population of 104 subjects with premature cervical shortening at randomization, the cervical length also differed significantly on multivariable analysis, with the treatment group preserving more cervical length than the placebo group (difference 3.3 (95% CI,.2) mm; P = 0.03, ANCOVA), with adjustment for differences in cervical length at screening. A significant difference was also observed between groups for categorical outcomes including the frequency of cervical length progression to ≤ 25 mm and a ≥ 50% reduction in cervical length from baseline in this subpopulation. ConclusionsIntravaginal progesterone enhances preservation of cervical length in women at high risk for preterm birth.

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“…The human placenta has been shown to express both subtypes of CRH receptors (Florio et al 2000). More recently, Jeschke and colleagues showed that the addition of CRH to the placental trophoblast cultures resulted in a decrease in progesterone release (Jeschke et al 2005). However, the effect of CRH produced locally in the placental trophoblasts on progesterone biosynthesis, and a detailed and quantitative analysis of the effects of CRH on all the enzymes needed for progesterone production as well as the specific CRH receptors responsible for the actions of CRH have not been performed.…”

Section: Introductionmentioning

confidence: 99%

Corticotropin-releasing hormone inhibits progesterone production in cultured human placental trophoblasts

Yang¹,

You²,

Tang³

et al. 2006

Journal of Molecular Endocrinology

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Placental-derived corticotropin-releasing hormone (CRH) seems to play a major role in the mechanisms controlling human pregnancy and parturition. It has been suggested that CRH directly modulates the endocrine function of placental trophoblasts, including the production of estrogen, ACTH, and prostaglandin. In this study, we sought to investigate the effect of CRH, locally produced by placenta, on progesterone production. Percoll-purified placental trophoblasts were obtained from uncomplicated term pregnancies and cultured for 72 h. Progesterone concentration in culture media was measured by RIA. The mRNA transcripts encoding CYP11A1 and HSD3B1, the enzymes for progesterone synthesis, were determined by quantitative real-time reverse transcription (RT)-PCR. Results showed that CRH (10K6 mol/l) caused a significant decrease in progesterone levels in a dose-dependent manner. The CRH antagonist, a-helical CRH 9-41, at 10K5 mol/l stimulated progesterone secretion. Consistent with this thesis, CRH decreased, whereas a-helical CRH increased, the mRNA levels of CYP11A1 and HSD3B1. Since CRH has been shown to activate the phospholipase C-protein kinase C (PKC) signal pathway in placenta, we examined whether the effect of CRH on progesterone synthesis was dependent on PKC signal pathway. Treatment of cells with PKC inhibitor, Gö 6976, resulted in a significant increase in progesterone production, and exogenous CRH restored progesterone production. In conclusion, placental CRH exhibits a tonic inhibitory effect on progesterone production in a PKC-dependent fashion.

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Regulation of progesterone production in human term trophoblasts in vitro by CRH, ACTH and cortisol (prednisolone)

Cited by 20 publications

References 37 publications

Placental Corticotrophin‐Releasing Hormone and its Receptors in Human Pregnancy and Labour: Still a Scientific Enigma

Placental Corticotrophin‐Releasing Hormone and its Receptors in Human Pregnancy and Labour: Still a Scientific Enigma

Effect of progesterone on cervical shortening in women at risk for preterm birth: secondary analysis from a multinational, randomized, double‐blind, placebo‐controlled trial

Corticotropin-releasing hormone inhibits progesterone production in cultured human placental trophoblasts

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