Decrease in functional activity of G-proteins hormone-sensitive adenylate cyclase signaling system, during experimental type II diabetes mellitus

The development of experimental type II diabetes mellitus in rats was accompanied by dysfunction of inhibitory and stimulatory heterotrimeric G-proteins, components of hormone-sensitive adenylate cyclase signal system. The function of inhibitory G-proteins decreased most significantly under these conditions, which is seen from weakened regulatory effects of somatostatin (in the myocardium) and bromocriptine (in the brain striatum) realized via inhibitory G-proteins in diabetic rats compared to controls. These hormones produce less pronounced inhibitory effect on forskolin-induced activation of adenylate cyclase. In the myocardium of diabetic rats, the stimulatory effects of isoproterenol and relaxin on adenylate cyclase realized via stimulatory G-proteins were decreased to a lesser extent. In the striatum of diabetic rats the stimulatory effect of serotonin and relaxin did not differ from the control. Therefore, dysfunction of stimulatory G-proteins during type II diabetes mellitus is characterized by tissue specificity. Synthetic peptides corresponding to functionally important regions in α-subunits of G-proteins and relaxin receptor LGR7 less effectively inhibited hormone signal transduction via the adenylate cyclase system in rats with type II diabetes. These changes reflect abnormal coupling between receptors and G-proteins in tissues of diabetic rats. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 142, No. 12, pp. 641–645, December, 2006     

On the receptor binding site of relaxins

Relaxin plays a critical role in viviparity and has recently been implicated as a hormone of oviparity as well. In most mammals relaxin causes the widening of the birth canal during parturition and suppresses uterine motility during pregnancy. Relaxins isolated from several species have shown a great deal of sequence variability, and speculations regarding a putative receptor interaction site have, as a consequence, varied considerably. The isolation of skate relaxin in combination with our chemical modification data enable us to suggest a unique site for the interaction of relaxin with its uterine and symphyseal receptors.     

Identification and characterization of the mouse and rat relaxin receptors as the novel orthologues of human leucine-rich repeat-containing G-protein-coupled receptor 7

1. Relaxin is an extracellular matrix (ECM)-remodelling hormone that is functionally important in reproductive tissues, brain, lung and heart. 2. Recently, the human relaxin receptor was identified as leucine-rich repeat-containing G-protein-coupled receptor 7 (LGR7). 3. Using human LGR7 as a template, we identified mouse and rat LGR7 orthologues in the Celera and National Centre for Biotechnology Information databases. 4. At the protein level, mouse and rat LGR7 share 85.2 and 85.7% identity with human LGR7, respectively. 5. Mouse LGR7 mRNA was detected in all tissues where relaxin binding is observed. 6. Mouse and rat LGR7 bound [33P]-relaxin with high affinity and, upon relaxin treatment, both receptors stimulated cAMP production in transfected HEK 293T cells. 7. These results indicate that mouse and rat LGR7 are the relaxin receptors in these species. 8. The actions of relaxin in rodents are well characterized, providing an established platform for research into the molecular pharmacology of the highly conserved relaxin receptor.     

Role of phosphatidylinositol-3-kinase and protein kinase Cζ in the adenylate cyclase signal mechanism of action of relaxin in muscle tissues of rats and mollusks

We showed that phosphatidylinositol-3-kinase and protein kinase C are involved in the adenylate cyclase signal mechanism of relaxin action. A selective inhibitor of phosphatidylinositol-3-kinase wortmannin blocked the stimulatory effect of relaxin on adenylate cyclase in rat skeletal muscles and Anodonta cygnea smooth muscles. Antibodies against protein kinase C abolished the relaxin-induced stimulation of adenylate cyclase in rat muscles, but not in mollusk muscles. Our results indicate that phosphatidylinositol-3-kinase and protein kinase C play a role in the adenylate cyclase signal mechanism of relaxin action.Translated from Byulleten Eksperimentalnoi Biologii i Meditsiny, Vol. 138, No. 10, pp. 420–423, October, 2004     

Effects of relaxin and IGF-I on capacitation, acrosome reaction, cholesterol efflux and utilization of labeled and unlabeled glucose in porcine spermatozoa

Aim:  Relaxin and insulin-like growth factor (IGF)-I have pronounced effects on the male and female reproductive tracts. The aim of this study was to investigate the effects of relaxin and IGF-I on the motility, capacitation, acrosome reaction, cholesterol efflux and utilization of glucose in porcine spermatozoa.
Methods:  Swim-up separated spermatozoa that had been washed twice were incubated at 37°C for 1 or 4 h in modified Tyrode's albumin lactate pyruvate (mTALP) medium supplemented without (control) or with relaxin (20 ng/mL) or IGF-I (20 ng/mL) or both (10 + 10 ng/mL).
Results:  Progressive motility and the induction rate of capacitation and acrosome reaction were increased ( P <  0.05) by relaxin and IGF-I alone or in combination, especially after 4 h of incubation. Relaxin alone or combined with IGF-I enhanced ( P  < 0.05) the cholesterol efflux after 4 h, whereas IGF-I alone did not show any significant effect on the cholesterol efflux compared with the control at any time point. The utilization rates of labeled and unlabeled glucose increased ( P <  0.05) in spermatozoa incubated with relaxin or IGF-I alone or in combination compared with the control.
Conclusion:  Thus, supplementation of relaxin alone or combined with IGF-I into the medium possibly plays a beneficial role in porcine spermatozoal prefertilization events in vitro . (Reprod Med Biol 2008; 7 : 29–36)     

Serum relaxin‐3 hormone relationship to male delayed puberty

Puberty is the transitional period between childhood and adulthood, a process encompassing morphological, physiological and behavioural development to attain full reproductive capability. This study aimed to assess serum relaxin‐3 hormone relationship with male delayed puberty. Sixty males were investigated as two equal groups: males with delayed puberty and healthy matched males as controls. They were subjected to history taking, clinical examination and estimation of serum FSH, LH, testosterone, relaxin‐3 hormonal levels. The results showed that the secondary sexual characters in the patients group were at Tanner stages 1–2 and in the healthy controls at Tanner stages 3–5. The mean BMI in the patients group was significantly increased, whereas the mean levels of the span, testicular volume, serum LH, FSH, testosterone as well as relaxin‐3 hormonal levels were significantly decreased compared with the healthy controls. Serum relaxin‐3 levels showed significant positive correlation with the age, testis volume, span, Tanner stages, serum testosterone, FSH, LH hormones. In addition, serum relaxin‐3 levels showed significant negative correlation with BMI. It is concluded that serum level of relaxin‐3 hormone is an important mediator in the pathophysiological process of normal puberty being significantly decreased in males with delayed puberty.     

Relaxin inhibits effective collagen deposition by cultured hepatic stellate cells and decreases rat liver fibrosis in vivo

BACKGROUND: Following liver injury, hepatic stellate cells (HSC) transform into myofibroblast-like cells (activation) and are the major source of type I collagen and the potent collagenase inhibitors tissue inhibitors of metalloproteinases 1 and 2 (TIMP-1 and TIMP-2) in the fibrotic liver. 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. AIMS: To determine the effects of relaxin on activated HSC. METHODS: Following isolation, HSC were activated by culture on plastic and exposed to relaxin (1-100 ng/ml). Collagen deposition was determined by Sirius red dye binding and radiolabelled proline incorporation. Matrix metalloproteinase (MMP) and TIMP expression were assessed by zymography and northern analysis. Transforming growth factor beta1 (TGF-beta1) mRNA and protein levels were quantified by northern analysis and ELISA, respectively. RESULTS: Exposure of activated HSC to relaxin resulted in a concentration dependent decrease in both collagen synthesis and deposition. There was a parallel decrease in TIMP-1 and TIMP-2 secretion into the HSC conditioned media but no change in gelatinase expression was observed. Northern analysis demonstrated that primary HSC, continuously exposed to relaxin, had decreased TIMP-1 mRNA expression but unaltered type I collagen, collagenase (MMP-13), alpha smooth muscle actin, and TGF-beta1 mRNA expression. CONCLUSION: These data demonstrate that relaxin modulates effective collagen deposition by HSC, at least in part, due to changes in the pattern of matrix degradation.     

心身放松疗法对高血压患者血压及生活质量的影响

目的　探讨心身放松疗法治疗原发性高血压患者的临床疗效及对其生活质量的影响。方法　将新发现的轻、中度高血压患者60例随机分为实验组(心身放松疗法) 和对照组(常规治疗), 疗程为4周。两组的临床疗效通过血压和成套生活质量量表评估。结果　治疗4周后, 两组患者的收缩压和舒张压与治疗前差异均有显著性意义(P<0. 01), 组间比较差异无显著性意义(P>0. 05); 实验组患者治疗前、后躯体症状、生活满意指数、健康愉快感及老年抑郁指数的评分间差异有显著性意义(P<0 .05), 对照组除躯体症状外其余各指标间差异均无显著性意义(P>0 .05)。结论　心身放松疗法具有改善高血压患者生活质量以及降低血压的作用, 适用于轻、中度原发性高血压患者。     

Is maternal serum relaxin associated with preterm delivery in Chinese pregnant women? A meta-analysis

Objective: A meta-analysis was performed to study the relationship between serum relaxin and preterm delivery in women with singleton pregnancies without estrogen stimulation.

Methods: Cohort and case-control studies were identified through searching databases (PubMed, Embase, Ovid, CBM, Wan fang, VIP, and CNKI). We carried out a continuous variable meta-analysis. The outcome was preterm delivery (gestation age <37 weeks).

Results: Fifteen studies were included, involving 1607 women with a singleton pregnancy. The pooled standard mean deviation (SMD) of 15 studies was 0.559 (95%CI: 0.002–1.196) and the heterogeneity was 96.6%. To reduce the heterogeneity, we chose random effects model and made subgroup analysis according to gestational age at sample testing (<18 weeks and ≥18 weeks) and race of included pregnant women. The pooled SMD of gestational age at sample testing ≥18 weeks and Chinese were 1.19 (95%CI: 0.63–1.75) and 1.61 (95%CI: 0.82–2.41) and the heterogeneity values (measured by I²) were 93.5% and 76.5%, respectively.

Conclusions: Elevated maternal serum relaxin of later than 18 weeks of gestational age is associated with singleton preterm birth in Chinese women. It might be an important information to prevent singleton preterm delivery in Chinese women. What’s already known about this topic? Previous reports reveal that there is a relationship between elevated maternal serum relaxin and preterm birth. However, the included articles contained twin pregnancies and estrogen stimulation, which obviously resulted in higher relaxin concentrations. What does this study add?