Biology of reproduction
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Biology of reproduction · Jan 2001
Female steroid hormones modulate receptors for nerve growth factor in rat dorsal root ganglia.
Calcitonin gene-related peptide (CGRP) is a vasodilatory peptide, and it is primarily synthesized in dorsal root ganglia (DRG). Plasma CGRP levels increase during pregnancy and with steroid hormones, and nerve growth factor (NGF) stimulates calcitonin/CGRP promoter and CGRP synthesis in DRG. We previously showed that CGRP levels in DRG were stimulated with steroid hormone treatments in vivo but not in vitro. ⋯ In addition, the combination of these steroid hormones had more effect on both receptors than either hormone alone. Thus, we concluded that high levels of female steroid hormones such as those due to pregnancy or hormonal replacement therapy could increase NGF receptor expression in DRG that carry more NGF to elevate the CGRP synthesis in these groups. We suggested that the regulation of NGF receptors by ovarian steroids may underlie steroidal regulation of other factors such as CGRP.
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Biology of reproduction · Apr 2000
Regulation of calcitonin gene-related peptide expression in dorsal root ganglia of rats by female sex steroid hormones.
Calcitonin gene-related peptide (CGRP), a potent vasodilator primarily synthesized in dorsal root ganglia (DRG) neurons, has been shown to decrease vascular resistance and thus regulate blood flow to a variety of organs in rats. Serum CGRP levels in the human have been reported to increase with pregnancy and decrease postpartum. It has been suggested that female sex steroid hormones play a role in cardiovascular function, but the mechanisms are unknown. ⋯ In summary, both E(2) and P(4), either alone or in combination, stimulate CGRP peptide synthesis in DRG neurons through increasing CGRP mRNA. The effects of these steroid hormones are mediated through amplifying the NGF-induced synthesis of CGRP in these neurons. Thus, we propose that the cardiovascular functions of female sex steroid hormones may be mediated, at least in part, by the up-regulation of neuronal CGRP synthesis, via NGF-mediated mechanisms.
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Biology of reproduction · Feb 1999
Effect of oxytocin receptor and beta2-adrenoceptor blockade on myometrial oxytocin receptors in parturient rats.
It has been proposed that the rise in myometrial oxytocin receptor (OTR) concentrations at term triggers parturition. In the present study, we have shown that in vivo infusion of the beta2-adrenoceptor (beta2AR) antagonist ICI-118.551 in late pregnant rats prevents the rise in myometrial OTR binding normally seen during delivery. A reduced contractile responsiveness of uterine strips isolated from rats in labor when challenged with oxytocin (OT) and a slight shortening of gestation accompanied this effect. ⋯ We further suggest that OTR stimulation up-regulates OTR during labor. The OTR down-regulation seen after atosiban treatment adds to the direct relaxing effect of atosiban on the myometrium. In view of this, atosiban may prove to be a more useful tocolytic than the traditionally used beta2 agonists.
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Biology of reproduction · Jan 1998
Comparative StudyDifferences in the in vitro sensitivity of ovine myometrium and mesometrium to oxytocin and prostaglandins E2 and F2alpha.
We compared the in vitro response to oxytocin, prostaglandin (PG)E2, and PGF2alpha of myometrium and mesometrium from six ovariectomized ewes and 53 ewes at 106-145 days gestational age (dGA), including 14 ewes in spontaneous or betamethasone-induced labor. Myometrial baseline activity increased from 217+/-27 mN/cm2 of cross-sectional area (mean +/-SEM) in ovariectomized ewes to a plateau of 696+/-39 mN/cm2 at 126-135 dGA. No gestation-related changes were observed in mesometrial baseline activity. ⋯ During pregnancy, the myometrial pD2 of both PGs was one order of magnitude higher than the mesometrial pD2. The results indicate an increase in myometrial uterotonic receptor-mediated activity that precedes labor with no increase at labor, suggesting that in sheep, activation of the basic mechanisms responsible for strength of myometrial activity at labor occurs by 135 dGA. The greater sensitivity of the myometrium than the mesometrium to PGs supports a major role for intrauterine paracrine factors in regulating myometrial contractility.
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Biology of reproduction · Aug 1997
Effect of the oxytocin antagonist atosiban (1-deamino-2-D-tyr(OET)-4-thr-8-orn-vasotocin/oxytocin) on nocturanl myometrial contractions, maternal cardiovascular function, transplacental passage, and fetal oxygenation in the pregnant baboon during the last third of gestation.
The oxytocin antagonist, atosiban (1-deamino-2-D-tyr(OET)-4-thr-8-orn-vasotocin/oxytocin), was infused i.v. to chronically instrumented pregnant baboons in the last third of pregnancy. Atosiban (6 microg/kg per min) inhibited myometrial electromyographic activity associated with spontaneous myometrial contractions that occurred around the onset of darkness between 134 and 162 days gestation (term 180 days gestation). The effect of atosiban on maternal heart rate was minimal. ⋯ Maternal atosiban clearance rates were 9.2-16.9 ml/kg per min. In conclusion, atosiban was very effective at inhibiting spontaneously occurring nocturnal myometrial contractions during the last third of gestation in the pregnant baboon. Although atosiban crosses the placenta relatively freely, there was no effect on fetal oxygenation.