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Reduced Expression of Corticotropin-Releasing Hormone Receptor Type-1 in Human Preeclamptic and Growth-Restricted Placentas

The Sir Quinton Hazel Research Centre for Molecular Medicine, Department of Biological Sciences (E.Ka., E.W.H., D.K.G.), University of Warwick, Coventry CV4 7AL, United Kingdom; and University of Crete, Division of Medicine, Department of Obstetrics and Gynecology (A.G., E.Ko.), Heraklion, Crete, Greece 71110

Address all correspondence and requests for reprints to: Dr. D. K. Grammatopoulos, Department of Biological Sciences, University of Warwick, Coventry CV4 7AL, United Kingdom. E-mail: dgrammatopoulos{at}bio.warwick.ac.uk.

Placentally derived CRH seems to play a major role in the mechanisms controlling human pregnancy and parturition, via activation of specific receptors widespread in reproductive tissues. In the human placenta, CRH seems to modulate vasodilation, prostaglandin production, and ACTH secretion. It has also been suggested that CRH might act as a placental clock, determining the length of gestation. In addition, maternal plasma CRH concentrations are further elevated in pregnancies associated with abnormal placental function, such as preeclampsia and intrauterine growth retardation (IUGR).

In this study, we sought to investigate the expression of CRH-R1 levels in placentas from women who have undergone normal deliveries (control group) and patients who have been diagnosed as having preeclampsia or IUGR. Results showed that placental CRH-R1 mRNA levels (as shown by quantitative RT-PCR) and protein levels (shown by Western blotting analysis) were significantly (P < 0.05) reduced in all of the complicated pregnancies. In contrast, levels of the angiotensin II receptor were elevated in preeclampsia and reduced in IUGR subjects, as shown by RT-PCR and Western blotting analysis. These findings might suggest that changes in receptor expression may contribute toward dysregulation of the dynamic balance controlling vascular resistance.

This study was funded by Wellcome Trust. D.K.G. is a Wellcome Trust Career Development Research Fellow.

Abbreviations: AT₁-R, Angiotensin II receptor; B₂, bradykinin B₂; CRH-R, CRH receptor; SDS, sodium dodecyl sulfate; IUGR, intrauterine growth retardation.

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