Rabbit alveolar beta-adrenergic receptors increase with gestational age.

Pulmonary beta-adrenergic receptors, which mediate the actions of endogenous catecholamines, increase before birth, an important step in pulmonary maturation. This increase, which occurs primarily in the alveoli, may be hastened by corticosteroids. However, because the lung is composed of more than 40 cell types, we asked whether the normal distribution of beta-adrenergic receptors changes with gestational age in a way that seems physiologically relevant. We compared lungs from fetal rabbits at 26 and 31 days' gestation with lungs from adult rabbits by autoradiography with 125iodocyanopindolol, a beta-adrenergic antagonist. While the total silver grain concentration increased during gestation, the greatest proportional increase occurred in the alveoli. We conclude that pulmonary beta-adrenergic receptor concentration increases during gestation and that this increase is most dramatic for alveoli. This pattern is consistent with that previously observed after treatment of fetal rabbits in utero with corticosteroids.

Rabbit myometrial oxytocin and alpha 2-adrenergic receptors are increased by estrogen but are differentially regulated by progesterone.

Both myometrial oxytocin and alpha 2-adrenergic receptors are induced by estrogen. To compare the regulation of these two receptor populations by progesterone, we measured myometrial receptor concentration in ovariectomized steroid-treated and in pregnant rabbits. To control for the effects of estrogen withdrawal, we used concomitant rather than sequential presentation of estrogen and progesterone in ovariectomized rabbits. Estradiol increased both myometrial oxytocin and alpha 2-adrenergic receptor concentrations in ovariectomized rabbits after 8 days of treatment. Simultaneous progesterone administration during the last 4 days of estradiol treatment reversed the induction of oxytocin, but not alpha 2-adrenergic, receptors. Similarly, administration of the antiprogestin RU 38486 to pregnant rabbits on day 27 of gestation resulted in premature delivery and evoked an increase in myometrial oxytocin receptor concentration mimicking that observed at term (day 31). However, RU 38486 did not significantly affect alpha 2-adrenergic receptor concentration. Our data provide further support for involvement of oxytocin receptors in parturition, but do not indicate a comparable function for myometrial alpha 2-adrenergic receptors.

Rabbit uterine oxytocin receptors and in vitro contractile response: abrupt changes at term and the role of eicosanoids.

We examined the relation between increased uterine oxytocin receptor concentration and increased in vivo sensitivity of the rabbit uterus to oxytocin at the end of gestation. We determined oxytocin receptor concentrations in myometrium and decidua on different days near term of gestation and postpartum. We also examined the in vitro contractile response to oxytocin on days 30 and 5 days postpartum, when the uterus is unresponsive in vivo, and on day 31 (term), when the uterus is exquisitely sensitive to this hormone in vivo. In addition, we tested the role of endogenous eicosanoids and decidual oxytocin receptors in the myometrial contractile response to oxytocin by examining the contractile response in the presence of the cyclooxygenase/lipoxygenase inhibitor sodium meclofenamate or in muscle strips from which the decidua had been removed by scraping. The concentration of specific binding sites for [3H]oxytocin in myometrial and also decidual membrane preparations was determined. We demonstrate that contractile sensitivity to oxytocin increases at least 4-fold between days 30 and 31 (term) of gestation, and this is accompanied by a nearly 10-fold increase in the concentration of oxytocin-binding sites in both decidua and myometrium. The lesser sensitivity to oxytocin on day 30 was, however, only apparent in the presence of meclofenamate, which suggests that endogenous eicosanoids contribute to the preterm response to oxytocin measured in vitro. The maximal response to oxytocin (integrated area) increased 2-fold between day 30 and term. Thus, an increase in both sensitivity and maximal response to oxytocin could be demonstrated at term in vitro. Five days after parturition, maximal response and uterine sensitivity measured in the presence of meclofenamate had returned to those of the preterm uterus, and the concentration of oxytocin-binding sites had declined. In contrast, sensitivity and maximal response to the cholinergic agonist carbamylcholine declined between day 30 and term. These results support a highly regulated physiological role for oxytocin in parturition which depends primarily on changes in receptor concentration.