Synthesis and metabolism of oxytocin in late gestation in human decidua.

Jan 1, 1995Advances in experimental medicine and biology

Production and use of oxytocin in the human womb lining during late pregnancy

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Abstract

A three-fold increase in the rate of synthesis of oxytocin mRNA occurs in human decidua around the time of parturition.

Oxytocin may be synthesized in a paracrine manner within the pregnant human uterus, influencing the timing of childbirth.
Physiological concentrations of estradiol can stimulate increases in both oxytocin mRNA and peptide synthesis in vitro.
The estrogen receptor blocker tamoxifen and transcription inhibitors can inhibit the increase in oxytocin synthesis.
High concentrations of estrogen receptors were found to increase significantly around the time of labor onset, while progesterone had minimal effect.
Local concentrations of oxytocin appear to be regulated by synthesis rates rather than metabolic rates, with no significant changes in metabolic parameters observed around parturition.

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Several studies in the past few years have supported the hypothesis that oxytocin (OT) is synthesized in a paracrine system within the pregnant human uterus and that this paracrine system may be an important regulator of the timing of human parturition. Using ribonuclease protection assays, we have demonstrated a three-fold increase in the rate of synthesis of OT mRNA in human decidua around the time of parturition. We also have shown that a similar increase in OT mRNA and peptide synthesis can be stimulated in vitro by physiological concentrations of estradiol. This increase is inhibited by concomitant use of the estrogen receptor (ER) blocker tamoxifen or by transcription inhibitors. Progesterone had little, if any effect. We also detected mRNAs for ER and progesterone receptor (PR) in amnion, chorion and decidua with the same relative tissue concentrations as OT mRNA. The concentrations of ER but not PR increased significantly around the time of labour onset. To determine if local OT concentrations may be regulated by changes in OT metabolism, we determined kinetic parameters for OT metabolism in decidua, chorion and placenta. [3H]tyrosyl-OT was used as substrate. Metabolites were separated using HPLC and identified using amino acid analysis and mass spectrometry. Metabolism in decidua and chorion occurred predominantly via a cytosolic post-proline endopeptidase and the activity was comparable to placenta. In microsomal fractions, cystine aminopeptidase activity predominated and placenta had significantly more activity than decidua and chorion. There were no changes in any Km or apparent vmax values around the time of parturition. These findings support the existence of a paracrine system within human decidua that involves sex steroids regulating synthesis of OT and that undergoes significant changes around the time of parturition. Changes in local OT concentrations are controlled by rates of synthesis rather than rates of metabolism.

Synthesis and metabolism of oxytocin in late gestation in human decidua.

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