The Development of a Radioimmunoassay for Oxytocin: The Extraction of Oxytocin From Plasma, and Its Measurement During Parturition in Human and Goat Blood

Chard, T.; Boyd, N. R. H.; Forsling, Mary L.; McNeilly, Alan S.; Landon, J.

doi:10.1677/joe.0.0480223

Cited by 148 publications

(66 citation statements)

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“…Exogenously induced OT elevation has been reported to impair the development of rat offspring at birth and during postnatal stages (44). In this context, OT has been shown to influence the developing heart; OT administered in excess to the fetus may inhibit cardiac growth in humans and rats (45,46). Conversely, OTR suppression by OTA in the early stage of chicken egg development leads to cardiac malformation in the embryos, which suggests the importance of OT in the cardiac development of birds.…”

Section: Discussionmentioning

confidence: 99%

Oxytocin in cardiac ontogeny

Jankowski

Danalache²,

Wang³

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

103

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Previous studies demonstrated the presence of oxytocin (OT) and oxytocin receptors (OTRs) in the heart. The present work provides results supporting a potential role of OT in cardiomyogenesis. Here, we show a maximal OT and OTR protein level in the developing rat heart at day 21 of gestation and postnatal days 1-4, when cardiac myocytes are at a stage of intense hyperplasia. Between postnatal days 1 and 66, OT decreased linearly in all heart chambers (4.1-to 6.6-fold). Correspondingly, immunocytochemistry demonstrated that OTRs, which were eminent in postnatal cardiomyocytes, declined with age to low levels in adults. Interestingly, in coronary vasculature, OTRs developed in endothelial cells at postnatal days 12 and 22 and achieved a plateau in adult rats. These findings suggest that OT can be involved in developmental formation of the coronary vessels. In vivo, the OT͞OTR system in the fetal heart was sensitive to the actions of retinoic acid (RA), recognized as a major cardiac morphogen. RA treatment produced a significant increase (2-to 3-fold) both in the OT concentration and in the OT mRNA levels. Ex vivo, an OT antagonist inhibited RA-mediated cardiomyocyte differentiation of P19 embryonic stem cells. The decline of cardiac OT expression from infancy to adulthood of the rat and changes in cell types expressing OTR indicate a dynamic regulation of the OT system in the heart rather than constitutive expression. The results support the hypothesis that RA induces cardiomyogenesis by activation of the cardiac OT system. heart development ͉ oxytocin receptors ͉ retinoic acid ͉ oxytocin antagonist ͉ cardiomyocyte differentiation O xytocin (OT), recognized traditionally as a reproductive hormone with a major role in childbirth and lactation, is produced in high concentrations in the hypothalamic supraoptic nucleus and paraventricular nucleus, then transported from these source nuclei to the posterior pituitary by neurosecretion (1). Longitudinal studies of neural and hormonal circuits activated by experimental volume expansion have identified OT as a major regulator of cardiovascular functions (reviewed in refs. 2 and 3). OT, injected peripherally, causes a decrease of arterial pressure (4) while reducing both heart rate and the force of contractions in isolated atria (5). OT acts via neuroendocrine͞ endocrine͞paracrine pathways to release atrial natriuretic peptide (ANP) from the heart (6, 7). ANP is a potent diuretic, natriuretic, and vasorelaxant hormone that is also involved in cell growth regulation. In addition, we have demonstrated that in isolated, perfused hearts, an OT antagonist (OTA) blocks basal ANP release (7), suggesting the presence of local OT in the heart. Further study revealed cardiac OT synthesis (8), with OT being detected in the medium of cultured neonatal rat cardiomyocytes (9).Recently, we showed that P19 embryonic carcinoma cells, a model of mouse embryonic stem cells, express OT receptors (OTRs), and OT stimulates the differentiation of these cells into beating cell colonies expressing ...

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Section: Discussionmentioning

confidence: 99%

Oxytocin in cardiac ontogeny

Jankowski

Danalache²,

Wang³

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

103

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“…The possibility that OT has trophic effects on the embryo has not been investigated intensively. However, OT has been shown to have an influence on the developing heart: OT administered in excess to the fetus may impair cardiac growth in humans and rats (19,20), and OTR suppression by specific OT antagonists (OTAs) in the early stage of chicken egg development leads to cardiac malformation in the embryos. ʈ It is not known whether the trophic effects of OT on the heart are direct or indirect.…”

mentioning

confidence: 99%

Oxytocin induces differentiation of P19 embryonic stem cells to cardiomyocytes

Paquin

Danalache

Jankowski

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

212

175

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We recently discovered the existence of the oxytocin͞oxytocin receptor (OT͞OTR) system in the heart. Activation of cardiac OTR stimulates the release of atrial natriuretic peptide (ANP), which is involved in regulation of blood pressure and cell growth. Having observed elevated OT levels in the fetal and newborn heart at a stage of intense cardiomyocyte hyperplasia, we hypothesized a role for OT in cardiomyocyte differentiation. We used mouse P19 embryonic stem cells to substantiate this potential role. P19 cells give rise to the formation of cell derivatives of all germ layers. Treatment of P19 cell aggregates with dimethyl sulfoxide (DMSO) induces differentiation to cardiomyocytes. In this work, P19 cells were allowed to aggregate from day 0 to day 4 in the presence of 0.5% DMSO, 10 ؊7 M OT and͞or 10 ؊7 M OT antagonist (OTA), and then cultured in the absence of these factors until day 14. OT alone stimulated the production of beating cell colonies in all 24 independently growing cultures by day 8 of the differentiation protocol, whereas the same result was obtained in cells induced by DMSO only after 12 days. Cells induced with OT exhibited increased ANP mRNA, had abundant mitochondria (i.e., they strongly absorbed rhodamine 123), and expressed sarcomeric myosin heavy chain and dihydropyridine receptor-␣1, confirming a cardiomyocyte phenotype. In addition, OT as well as DMSO increased OTR protein and OTR mRNA, and OTA completely inhibited the formation of cardiomyocytes in OT-and DMSO-supplemented cultures. These results suggest that the OT͞OTR system plays an important role in cardiogenesis by promoting cardiomyocyte differentiation.

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“…OT and OT receptor are expressed in the developing heart [Paquin et al, 2002;Jankowski et al, 2004]. Administration of OT to the fetus impairs cardiac growth in humans and rats, and suppression of OT receptor by specific OT antagonists in the early stage of chicken egg development leads to cardiac malformation in the embryos [Chard et al, 1970;Schriefer et al, 1982]. In vitro, the addition of OT to P19 embryonic cells stimulates the production of beating cardiomyocyte colonies, and addition of OT antagonists completely inhibits the formation of cardiomyocytes [Paquin et al, 2002].…”

Section: Erythropoietin (Epo)mentioning

confidence: 99%

Extrinsic regulation of cardiomyocyte differentiation of embryonic stem cells

Chen

Wang

2007

J of Cellular Biochemistry

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Cardiovascular disease is one of leading causes of death throughout the U.S. and the world. The damage of cardiomyocytes resulting from ischemic injury is irreversible and leads to the development of progressive heart failure, which is characterized by the loss of functional cardiomyocytes. Because cardiomyocytes are unable to regenerate in the adult heart, cell-based therapy of transplantation provides a potential alternative approach to replace damaged myocardial tissue and restore cardiac function. A major roadblock toward this goal is the lack of donor cells; therefore, it is urgent to identify the cardiovascular cells that are necessary for achieving cardiac muscle regeneration. Pluripotent embryonic stem (ES) cells have enormous potential as a source of therapeutic tissues, including cardiovascular cells; however, the regulatory elements mediating ES cell differentiation to cardiomyocytes are largely unknown. In this review, we will focus on extrinsic factors that play a role in regulating different stages of cardiomyocyte differentiation of ES cells.

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The Development of a Radioimmunoassay for Oxytocin: The Extraction of Oxytocin From Plasma, and Its Measurement During Parturition in Human and Goat Blood

Cited by 148 publications

References 0 publications

Oxytocin in cardiac ontogeny

Oxytocin in cardiac ontogeny

Oxytocin induces differentiation of P19 embryonic stem cells to cardiomyocytes

Extrinsic regulation of cardiomyocyte differentiation of embryonic stem cells

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