Disease relevance of Rln1

• Relaxin has antifibrotic effects on the hepatic stellate cells (HSCs) responsible for collagen deposition in cirrhosis [1].
• The expression of relaxin receptors LGR7 and LGR8 in HSCs and liver disease was examined [1].
• Relaxin (100 ng) was given intravenously 30 minutes before ischemia [2].
• Relaxin inhibits effective collagen deposition by cultured hepatic stellate cells and decreases rat liver fibrosis in vivo [3].
• These data indicate that relaxin-induced uterine edema and growth is mediated by ERs [4].

Psychiatry related information on Rln1

• A second set of experiments was done to examine the effects of neutralizing the central actions of relaxin on drinking behavior in pregnancy [5].

High impact information on Rln1

• Relaxin affects the release of oxytocin and vasopressin from the neurohypophysis [6].
• Recent experiments performed in vivo indicate that relaxin might act not only in the uterus, but also in the hypothalamus and possibly in the neurohypophysis [6].
• Intravenous injection of porcine relaxin in anaesthetized lactating rats inhibits milk ejection and injection of relaxin into the cerebral ventricles disturbs the pattern of the milk ejection reflex [6].
• Under basal conditions, vasopressin and oxytocin release was inhibited by relaxin but, when the nerve endings were depolarized, vasopressin and oxytocin secretion was potentiated [6].
• At this time high titres of relaxin are present in the plasma and there is evidence that the hormone has a direct inhibitory action on the uterine muscle [7].

Chemical compound and disease context of Rln1

• Following treatment with 17beta-estradiol or relaxin alone, the uterine weight/body weight ratio (UtW/BW) increased significantly over control values (+98% and +77% respectively, p<0.0003) [4].
• Pretreatment of cells with pertussis toxin or replacement of extracellular calcium with 2 mM EGTA inhibited the oxytocin-induced increase in intracellular calcium by 47% and 50%, respectively, but did not inhibit the action of relaxin [8].
• 6. Relaxin was much less potent against the spasm dependent upon intracellular Ca2+ (that induced by oxytocin (20 nM) + nifedipine (500 nM)) than against the spasms dependent upon extracellular Ca2+, those induced by oxytocin (0.2 nM) and Bay K 8644 (1 microM) [9].
• The depression in collagen concentration and increase in apparent rate of proline incorporation into collagen induced by relaxin alone were also eliminated, indicating a fundamental blockade of the effect of relaxin in this experimental design as well as a close association of changes in collagen concentration with tissue hypertrophy [10].
• Effect of relaxin on myocardial ischemia injury induced by isoproterenol [11].

Biological context of Rln1

• The nucleotide sequence of these clones demonstrates that relaxin is synthesized as a preprorelaxin molecule with an unexpectedly large connecting peptide of 105 amino acid residues [12].
• Comparison with porcine relaxin reveals a clear sequence homology but the extent of this is much more limited than expected, with only 21 of 53 residues (39.6%) in corresponding positions being identical [13].
• We have isolated rat relaxin as a single chromatographic component and determined its complete amino acid sequence [13].
• The major objectives of the present work were to determine whether relaxin administration to nonpregnant rats 1) modifies cardiac output (CO), systemic vascular resistance, and global arterial compliance (AC), and 2) regulates the passive mechanics of isolated arteries [14].
• Localization of LGR7 (relaxin receptor) mRNA and protein in rat forebrain: correlation with relaxin binding site distribution [15].

Anatomical context of Rln1

• Relaxin 3-immunoreactive fibers projected particularly densely in the septum, hippocampus, lateral hypothalamus and intergeniculate leaflet of the thalamus [16].
• Relaxin, a peptide hormone secreted by the corpus luteum during pregnancy, exerts actions on reproductive tissues such as the pubic symphysis, uterus, and cervix [17].
• Circulating relaxin acts on subfornical organ neurons to stimulate water drinking in the rat [17].
• Although ablation of the OVLT did not inhibit relaxin-induced drinking, it did cause a large reduction in Fos expression in the supraoptic nucleus and posterior magnocellular subdivision of the paraventricular nucleus [17].
• In another group of rats, relaxin administration also regulated the passive mechanics of small renal arteries, indicating that, in addition to reduction in vascular smooth muscle tone, modification of the vascular structure (e.g. extracellular matrix) contributes to the increase in global AC [14].

Associations of Rln1 with chemical compounds

• It is likely that circulating relaxin also stimulates neurons in the OVLT that influence vasopressin secretion [17].
• A novel, adenylate cyclase, signaling mechanism of relaxin H2 action [18].
• They also raise the likelihood of a role for relaxin in other cardiovascular changes of pregnancy, and they suggest that, like estrogen, relaxin should be considered a regulator of cardiovascular function [19].
• In contrast, the renal vasoconstrictory response to angiotensin II was attenuated by the RLX treatment [20].
• It is suggested that relaxin may have a physiological role in modulating mast cell function through the L-arginine-nitric oxide pathway [21].

Regulatory relationships of Rln1

• The ability of PRL or rat placental lactogen (rPL)-1 to induce relaxin mRNA expression was analyzed in a luteinized rat granulosa cell culture model [22].
• PRL receptor activation induced relaxin mRNA expression in a concentration- and time-dependent manner [22].
• Treatment of rats with 17beta-estradiol or relaxin rapidly inhibits uterine estrogen receptor beta1 and beta2 messenger ribonucleic acid levels [23].
• Relaxin affects the central control of oxytocin release [7].
• Relaxin stimulates plasminogen activator secretion by rat granulosa cells in vitro [24].

Other interactions of Rln1

• Relaxin 3/INSL 7 has recently been identified as a new member of the insulin/relaxin superfamily [16].
• Discrete neuronal populations in brain express relaxin and relaxin-3, and molecular studies have identified former-orphan, G-protein-coupled receptors LGR7 and GPCR135 as their native receptors [15].
• Relaxin administration resulted in increased Fos expression in the subfornical organ (SFO), organum vasculosum of the lamina terminalis (OVLT), median preoptic nucleus, and magnocellular neurons in the supraoptic and paraventricular nuclei [17].
• The reproductive hormone relaxin has been reported to reduce collagen and TIMP-1 expression by dermal and lung fibroblasts and thus has potential antifibrotic activity in liver fibrosis [3].
• To gain insight into the role of ERbeta in estrogen action, we examined the effects of estrogen and relaxin, a ligand-independent activator of ERs, on the expression of ERbeta1 and ERbeta2 mRNA in the uterus in vivo [23].

Analytical, diagnostic and therapeutic context of Rln1

• Molecular cloning and characterization of cDNA sequences coding for rat relaxin [12].
• In vitro single-unit recording of electrical activity of neurons in isolated slices of the SFO showed that relaxin (10(-7) M) added to the perfusion medium caused marked and prolonged increase in neuronal activity [17].
• Using a gravid rodent model, we employ two approaches to eliminate relaxin or its biological activity from the circulation: ovariectomy and administration of neutralizing antibodies [19].
• Using a biologically active 32P-labeled human relaxin, we have previously shown by in vitro autoradiography specific relaxin binding sites in rat uterus, cervix, and brain tissues [25].
• In contrast, the relaxin binding in the rat heart was not affected by castration or sex steroid treatment [26].

References