Zoology - Research Publications
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ItemNo Preview AvailableSteroid-independent regulation of uterine oxytocin receptors(WILEY, 2004-04)The oxytocin receptor is an important contractile-associated protein, up-regulated at term in the myometrium in many mammalian species. We conducted studies in a novel animal model to challenge the general view that gonadal steroids are a major regulatory factor of uterine oxytocin receptors. Female marsupials have separate uteri and, in monovular species such as the tammar wallaby, the conceptus is present in one uterus whereas the contralateral uterus is empty. A marked increase in myometrial oxytocin receptors occurs only in the gravid uterus. Fetectomy experiments demonstrated that local embryo-derived factors stimulate this gravid uterus-specific increase in oxytocin receptors, and that uterine distension is probably not a key component in this regulatory pathway. Unilateral ovariectomy has no significant effect on uterine oxytocin receptors, emphasizing the impact of the conceptus on oxytocin receptor regulation and the minimal influence of gonadal steroids on parturition in this species. Our data highlight that regulation of uterine oxytocin receptor expression is multifactorial, and does not necessarily rely on gonadal steroids.
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ItemNo Preview AvailableMechanisms of relaxin action in the reproductive tract -: Studies in the relaxin-deficient (Rlx-/-) mouse(NEW YORK ACAD SCIENCES, 2005)The major functions of relaxin (RLX) are associated with female reproductive tract physiology, namely, the regulation of biochemical processes involved in remodeling of extracellular matrix components in the cervix and vagina at term. Studies in RLX-deficient mice (Rlx-/-) demonstrate that although females give birth to live young without apparent dystocia, the pubic symphysis is not elongated, and they have abnormal cervical and vaginal morphology. The current study examined phenotypic differences in collagen, matrix metalloproteinases (MMP), and estrogen receptors (ERs) in the cervix and vagina of pregnant Rlx+/+ and Rlx-/- mice. Neither collagen nor TGFbeta1 mRNA levels in the cervix and vagina differed significantly between Rlx+/+ and Rlx-/- at any stage of gestation, except on gestation day 18.5, with an increase in alpha(1)-I collagen and TGFbeta1 expression in Rlx-/- mice. MMP gene expression was also increased in Rlx-/- mice, especially at term. Administration of recombinant H2 RLX (0.05 microg/microL/h) to Rlx-/- mice for 6 d from gestation day 12.5 caused a significant decrease in alpha1-I collagen and MMP-13 gene expression in the cervix and vagina, but it had no effect on TGFbeta1. There was also a significant reduction in ERbeta expression in RLX-treated Rlx-/- mice. Interestingly, RLX treatment caused a significant decrease in LGR7 expression in these reproductive tissues. In summary, these data show increases in MMP gene expression in Rlx-/- mice that are not correlated with changes in collagen expression. Furthermore, we report a novel ER phenotype in the cervix and vagina of Rlx-/- mice.
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ItemNo Preview AvailableOxytocin and estrogen receptor expression in the myometrium of pregnant relaxin-deficient (Rlx-/-) mice(NEW YORK ACAD SCIENCES, 2005)Relaxin decreases oxytocin-stimulated rat myometrial contractions in vitro. This study used pregnant relaxin-deficient (Rlx-/-) mice to investigate the interaction between relaxin, oxytocin receptor (OTR), and estrogen receptor (ER) expression in the myometrium. Myometrial OTRs were significantly decreased on gestation day 18.5 in Rlx-/- mice than in Rlx+/+ mice. An increase in ERalpha in Rlx+/+ mice at term was correlated with a decrease in ERbeta, which was not observed in Rlx-/- mice. Treatment of Rlx-/- mice with relaxin had no effect on OTR, LGR7, or ERalpha expression, but it caused a significant decrease in ERbetas.
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ItemA Vasoactive Role for Endogenous Relaxin in Mesenteric Arteries of Male Mice(PUBLIC LIBRARY SCIENCE, 2014-09-22)The peptide hormone relaxin has striking effects on the vascular system. Specifically, endogenous relaxin treatment reduces myogenic reactivity through nitric oxide (NO)-mediated vasorelaxation and increases arterial compliance in small resistance arteries. However, less is known about the vascular roles of endogenous relaxin, particularly in males. Therefore, we used male wild-type (Rln+/+) and relaxin knockout (Rln-/-) mice to test the hypothesis that passive wall properties and vascular reactivity in mesenteric arteries would be compromised in Rln-/- mice. Passive compliance was determined in arteries (n=8-9) mounted on a pressure myograph and in Ca2+-free Krebs containing 2 mM EGTA. Passive volume compliance was significantly (P=0.01) decreased in the mesenteric arteries of Rln-/- mice. Vascular reactivity was assessed using wire myography. In mesenteric arteries (n=5) of Rln-/- mice, there was a significant (P<0.03) increase in sensitivity to the vasoconstrictors phenylephrine and thromboxane-mimetic U41669. This enhanced responsiveness to vasoconstrictors was abolished by endothelial denudation, and attributed to impaired NO and prostanoid pathways in Rln-/- mice. Sensitivity to the endothelial agonist acetylcholine was significantly (n=7-9, P ≤ 0.03) decreased, and this was abolished in the presence of the cyclooxygenase inhibitor, indomethacin (2 µM). This indicates that prostanoid vasoconstrictor pathways were upregulated in the mesenteric arteries of Rln-/- mice. In summary, we demonstrate endothelial dysfunction and impaired arterial wall remodeling in male mice deficient in relaxin. Thus, our results highlight a role for endogenous relaxin in the maintenance of normal mesenteric artery structure and function in males.
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ItemImpaired vascular responses to relaxin in diet-induced overweight female rats(AMER PHYSIOLOGICAL SOC, 2012-03)Relaxin mediates renal and mesenteric vascular adaptations to pregnancy by increasing endothelium-dependent vasodilation and compliance and decreasing myogenic reactivity. Diet-induced overweight and obesity are associated with impaired endothelial dysfunction and vascular remodeling leading to a reduction in arterial diameter. In this study, we tested the hypothesis that local vascular responses to relaxin are impaired in diet-induced overweight female rats on a high-fat cafeteria-style diet for 9 wk. Rats were chronically infused with either relaxin or placebo for 5 days, and vascular responses were measured in isolated mesenteric arteries and the perfused kidney. Diet-induced overweight significantly increased sensitivity to phenylephrine (by 17%) and vessel wall thickness, and reduced renal perfusion flow (RPFF; by 16%), but did not affect flow-mediated vasodilation, myogenic reactivity, and vascular compliance. In the normal weight rats, relaxin treatment significantly enhanced flow-mediated vasodilation (2.67-fold), decreased myogenic reactivity, and reduced sensitivity to phenylephrine (by 28%), but had no effect on compliance or RPFF. NO blockade by l-NAME diminished most relaxin-mediated effects. In diet-induced overweight rats, the vasodilator effects of relaxin were markedly reduced for flow-mediated vasodilation, sensitivity to phenylephrine, and myogenic response compared with the normal diet rats, mostly persistent under l-NAME. Our data demonstrate that some of the vasodilator responses to in vivo relaxin administration are impaired in isolated mesenteric arteries and the perfused kidney in diet-induced overweight female rats. This does not result from a decrease in Rxfp1 (relaxin family peptide receptor) expression but is likely to result from downstream disruption to endothelial-dependent mechanisms in diet-induced overweight animals.