The role of oxytocin and regulation of uterine oxytocin receptors in pregnant marsupials

Abstract

The oxytocin-like peptide of most Australian marsupials is mesotocin, which differs from oxytocin by a single amino acid. This substitution has no functional significance as both peptides have equivalent affinity for and biological activity on the marsupial oxytocin-like receptor. A role for mesotocin in marsupial parturition has been demonstrated in the tammar wallaby where plasma mesotocin concentrations increase less than one minute before birth. Infusion of an oxytocin receptor antagonist at the end of gestation disrupts normal parturition, probably by preventing mesotocin from stimulating uterine contractions. In the absence of mesotocin receptor activation, a peripartum surge in prostaglandins is delayed which suggests a functional relationship between mesotocin, prostaglandin release and luteolysis. Female marsupials have anatomically separate uteri and in monovular species, such as the tammar wallaby, only one uterus is gravid with a single fetus whereas the contralateral uterus remains non-gravid. We have used this unique animal model to differentiate systemic and fetal-specific factors in the regulation of uterine function during pregnancy. The gravid uterus in the tammar wallaby becomes increasingly sensitive to mesotocin as gestation proceeds, with the maximum contractile response observed at term. This is reflected in a large increase in mesotocin receptor concentrations in the gravid uterus, and a downregulation in the non-gravid uterus in late pregnancy. The upregulation in myometrial mesotocin receptors is pregnancy-specific and independent of systemic steroids. One factor that may influence mesotocin receptor upregulation in the gravid uterus in late pregnancy is mechanical stretch of the uterus caused by the growing fetus. Our data highlight that a local fetal influence is more important than systemic factors in the regulation of mesotocin receptors in the tammar wallaby. Experimental Physiology (2000) 85S, 91s-99sMammals evolved from reptile-like ancestors sometime between the late Triassic and Cretaceous periods, 190-100 million years ago, into prototherians (or monotremes), metatherians (or marsupials) and eutherians. One of the main characteristics of mammals is their ability to provide offspring with milk in the immediate postnatal period. Essential for lactation is the production of the nonapeptide hormone oxytocin by the magnocellular neurones of the hypothalamus. Release of oxytocin from the posterior pituitary, induced by the sucking stimulus of the young, causes contractions of the myo-epithelial cells of the mammary gland which results in milk ejection. The other main physiological effect of oxytocin in eutherians is to stimulate smooth muscle contractions of the uterus during birth.

The Mitogen-Activated Protein Kinase Dependent Expression of Prostaglandin H Synthase-2 and Interleukin-8 Messenger Ribonucleic Acid by Myometrial Cells: The Differential Effect of Stretch and Interleukin-1β

“…This is supported by the observations that preterm labor is also increased in polyhydramnios (18), early birth is associated with a relatively greater birth weight (19), and abortion during the second trimester of pregnancy and labor at term can be induced by uterine distension achieved by the insertion and inflation of a 150-ml balloon (20,21). Furthermore, animal data show that uterine stretch is responsible for the increase in contraction-associated protein (CAP) oxytocin receptor (OTR), PGHS-2, and connexin-43 (22)(23)(24)(25). We have shown that stretch of human uterine myocytes in vitro enhances the expression of OTR, PGHS-2, and IL-8 mRNA (26 -28).…”

Up-Regulation of Mesotocin Receptors in the Tammar Wallaby Myometrium Is Pregnancy-Specific and Independent of Estrogen1

“…The affinity (K a ) of this receptor for 125 I-OTA is similar to that of the MTR in the myometrium of the pregnant tammar [14]. Unlike the brushtail possum and eutherians, the pregnant and nonpregnant tammar uterine MTR shows a higher affinity for MT and OT compared with AVP, LVP, and phenypressin, the latter two being the vasopressor peptides of the tammar wallaby [13]. The concentrations of the peptides or antagonists that inhibited 125 I-OTA binding by 50% (IC 50 ) were lower in nonpregnant tissues, but the receptor had the same order of ligand binding affinities compared with the MTR in pregnant tissues [14].…”

“…It is likely that this causes stretching of the myometrial smooth muscle. Recent data suggest that distension of the gravid uterus may be sufficient to trigger the upregulation in MTRs observed on Day 23 of pregnancy in the tammar wallaby [13].…”

“…It is believed that contractions initiated in the uterus result in the rapid expulsion of the fetus. MT is one of the key hormones regulating this contractile activity in marsupials [13]. From Day 20 of gestation to the day of birth (Day 26) in the tammar wallaby, the gravid uterus becomes increasingly sensitive to exogenous MT, which stimulates an increase in frequency and amplitude of in vitro myometrial contractions [14,15].…”

Prediction of vaginal delivery in pregnant women with a uterine scar

“…Это связано с тем, что окситоцин имеет небольшой период полураспада (не-сколько минут), находится в плазме крови в низких кон-центрациях по сравнению с другими гормонами. Боль-шинство авторов сообщают об увеличении уровней эндо-генного окситоцина на протяжении беременности и до-стижении максимальной его концентрации к моменту родов [12,18,19,20].…”