Intersection of the relaxin and estrogen signalling pathways in the uterus

Koos, Robert D.; Pillai, S. B.

doi:10.1007/978-94-017-2877-5_12

Cited by 3 publications

(1 citation statement)

References 51 publications

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“…Additionally, data generated in ovariectomized, pubertal gilts (Zaleski et al 1995) indicating that ten days of relaxin treatment failed to promote uterine growth in the absence of ovarian steroids (estrogen or progesterone), support the view that uterotrophic actions of relaxin are at least facilitated by steroid hormone receptor Uterotrophic effects of relaxin are estrogen receptor-dependent 947 activation. Studies involving the MCF-7 breast cancer cell line showed that relaxin could stimulate expression of an estrogen response element-luciferase reporter gene (Koos & Pillai 2001), indicating that signaling pathways affected by relaxin can also activate the ER in the absence of estrogen.…”

Section: Discussionmentioning

confidence: 99%

Uterotrophic effects of relaxin related to age and estrogen receptor activation in neonatal pigs

Yan

Ryan²,

Bartol³

et al. 2006

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While uterotrophic effects of relaxin are well documented, the mechanism through which relaxin promotes uterine growth is incompletely understood. Studies in rats suggest that relaxin-stimulated uterine edema depends on estrogen receptor (ER) activation. Here, neonatal pigs were used to investigate the interaction between relaxin and ER signaling pathways. Gilts were treated either at birth (postnatal day (PND) 0) (study 1) before the onset of endometrial ERa expression, or on PND 12 (study 2) after the onset of ERa expression. In study 1, gilts were treated with estradiol-17b or porcine relaxin for two days and uteri were collected on PND 2. In study 2, PND 12 gilts were treated with a single injection of the ER antagonist ICI 182,780 (ICI) or vehicle. Two hours later, gilts were given either estradiol-17b or porcine relaxin for two days. When administered for two days from birth (study 1), neither estradiol-17b nor relaxin affected uterine weight or protein content. However, uterine luminal epithelial height was greater in relaxin-than in vehicle-treated gilts. In contrast, in study 2, both estradiol and relaxin increased uterine weight, protein content and uterine luminal epithelial height on PND 14. These effects were inhibited by pre-treatment with ICI in both estradiol-and relaxin-treated gilts. The results indicate that uterotrophic effects of relaxin in the neonatal pig are related to age and to both the relative presence and state of activation of the ER system in developing uterine tissues between birth and PND 14.

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Section: Discussionmentioning

confidence: 99%

Uterotrophic effects of relaxin related to age and estrogen receptor activation in neonatal pigs

Yan

Ryan²,

Bartol³

et al. 2006

Reproduction

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Studies of the molecular mechanisms of action of relaxin on the adenylyl cyclase signaling system using synthetic peptides derived from the LGR7 relaxin receptor

Шпаков

Guryanov

Kuznetsova

et al. 2007

Neurosci Behav Physiol

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The peptide hormone relaxin produces dose-dependent stimulation of adenylyl cyclase activity in rat tissues (striatum, cardiac and skeletal muscle) and the muscle tissues of invertebrates, i.e., the bivalve mollusk Anodonta cygnea and the earthworm Lumbricus terrestris, adenylyl cyclase stimulation being more marked in the rat striatum and cardiac muscle. Our studies of the type of relaxin receptor involved in mediating these actions of relaxin involved the first synthesis of peptides 619-629, 619-629-Lys(Palm), and 615-629, which are derivatives of the primary structure of the C-terminal part of the third cytoplasmic loop of the type 1 relaxin receptor (LGR7). Peptides 619-629-Lys(Palm) and 615-629 showed competitive inhibition of adenylyl cyclase stimulation by relaxin in rat striatum and cardiac muscle but had no effect on the action of relaxin in rat skeletal muscle or invertebrate muscle, which is evidence for the tissue and species specificity of their actions. On the one hand, this indicates involvement of the LGR7 receptor in mediating the adenylyl cyclase-stimulating action of relaxin in rat striatum and cardiac muscle and, on the other, demonstrates the existence of other adenylyl cyclase signal mechanisms for the actions of relaxin in rat skeletal muscle and invertebrate muscle, not involving LGR7 receptors. The adenylyl cyclase-stimulating effect of relaxin in the striatum and cardiac muscles was found to be decreased in the presence of C-terminal peptide 385-394 of the alpha(s) subunit of the mammalian G protein and to be blocked by treatment of membranes with cholera toxin. These data provide evidence that in the striatum and cardiac muscle, relaxin stimulates adenylyl cyclase via the LGR7 receptor, this being functionally linked with G(s) protein. It is also demonstrated that linkage of relaxin-activated LGR7 receptor with the G(s) protein is mediated by interaction of the C-terminal half of the third cytoplasmic loop of the receptor with the C-terminal segment of the alpha(s) subunit of the G protein.

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Adenylyl cyclase signaling mechanisms of relaxin and insulin action: Similarities and differences

Pertseva

Kuznetsova

et al. 2006

Cell Biology International

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The adenylyl cyclase signaling mechanism (ACSM) of relaxin H2 action was discovered and deciphered in mammalian muscles. A study of signaling blocks involved in ACSM of relaxin in comparison with that of insulin previously detected showed a close similarity throughout the post-receptor signaling chain of both hormones. The inhibitory action of tyrosine kinase blockers on the hormone AC activating effect indicates that the relaxin receptor involved in ACSM is likely to be of the tyrosine kinase type. However, a recent discovery of a relaxin receptor with serpentine architecture leaves open the question concerning the existence of receptor of the tyrosine kinase type. The structural-functional organization of the ACSM due to the action of relaxin-shown here for the first time-can be presented as the following signaling sequence: relaxin receptor ==>G(i) protein (betagamma-dimer) ==>phosphatidylinositol 3-kinase ==>protein kinase Czeta ==>G(s) protein ==>adenylyl cyclase. According to our hypothesis, the regulatory action of the insulin superfamily peptides on cell processes (proliferation, apoptosis, and metabolism) is mediated via ACSM.

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Intersection of the relaxin and estrogen signalling pathways in the uterus

Cited by 3 publications

References 51 publications

Uterotrophic effects of relaxin related to age and estrogen receptor activation in neonatal pigs

Uterotrophic effects of relaxin related to age and estrogen receptor activation in neonatal pigs

Studies of the molecular mechanisms of action of relaxin on the adenylyl cyclase signaling system using synthetic peptides derived from the LGR7 relaxin receptor

Adenylyl cyclase signaling mechanisms of relaxin and insulin action: Similarities and differences

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