Serum Relaxin Research Articles

Time-resolved fluoroimmunoassay (TR-FIA) of porcine relaxin.

We developed and validated a new assay system for porcine relaxin that overcame the drawbacks of RIA by adapting time-resolved fluoroimmunoassay (TR-FIA), which was recently introduced as a non-RIA format. The assay system was a solid-phase TR-FIA based on competition for a polyclonal anti-porcine relaxin antibody between europium (Eu)-labeled porcine relaxin and test samples. Antibody-relaxin complexes were then bound to the second antibody coated on the solid phase, achieving rapid and complete separation of bound and free antigen. A standard curve was produced over the range of 1 pg/well to 1000 pg/well. Serum and corpus luteum extracts from pigs in late pregnancy exhibited inhibition curves parallel to that of the relaxin standard, whereas male pig serum caused no displacement of the labeled hormone. No cross-reactivity was seen with other hormones, such as insulin, LH, and FSH, indicating a high specificity of the assay. The sensitivity was 4 pg/well (80 pg/ml), which was high and equivalent to that of the porcine relaxin RIA. The intra-assay and inter-assay coefficients of variation were less than 3.8% and 6.7%, respectively. Recovery of porcine relaxin added to male pig serum sample averaged 103%. The advantages of this TR-FIA were that addition of tyrosine was not necessary for labeling, unlike the RIA, Eu-labeled relaxin was stable enough to allow long-term storage for more than one year, the assay was completed in only 5 h versus two to seven days for the RIA, and no special safety precautions were needed. To validate this TR-FIA, the serum relaxin concentrations during late pregnancy, parturition and early lactation were investigated in pigs. Serum relaxin levels determined by this assay were similar to those obtained previously by RIA. In conclusion, this TR-FIA could replace RIA as the method of choice for assay of relaxin.

Comparison of Selected Endocrine Parameters During Luteal Phase and Pregnancy in German Shepherd Dogs and Beagles

Concentrations of progesterone, prolactin and relaxin in serum at predetermined intervals after ovulation (day 0) in non-pregnant and pregnant normocyclic Beagles were assayed and results compared with those observed in German Shepherd dogs (GSD) in a previous study. The goal was to determine possible reproductive hormone specificities related to the GSD breed. Furthermore, the effects of medroxyprogesterone acetate (MPA)-treatment in non-pregnant Beagles and of progesterone supplementation in pregnant Beagles on the hormone concentrations were examined. Mean concentrations of progesterone and prolactin were not different in the non-pregnant Beagles compared with those seen in non-pregnant GSD, except at days 50-60, when progesterone concentrations were found to be higher in Beagles (p < 0.05). Mean progesterone concentrations in pregnant Beagles at days 50-60 after ovulation (day 0) were higher (p < 0.05) than in GSD at that time, but not at earlier time periods. Prolactin concentrations were higher (p < 0.05) in Beagles throughout pregnancy compared with those in the GSD. Mean relaxin concentrations were numerically but not significantly lower in GSD than in Beagles throughout pregnancy. A 10-day oral MPA treatment did not affect progesterone or prolactin secretion in normocyclic non-pregnant Beagles. Medroxyprogesterone acetate serum concentrations were approximately 3.9 ng/ml during treatment and decreased to 0.42 and 0.021 ng/ml within 5 and 15 days after end of treatment, respectively. Intramuscular progesterone supplementation from days 30 to 40 in pregnant Beagles resulted in higher concentrations of progesterone in the 36- to 45-day time periods; prolactin and relaxin concentrations were not significantly affected during or after treatment compared with administration of placebo. The results suggest a tendency towards deficient luteal function in the short-cycle GSD bitches previously studied, which in pregnancy may reflect the observed decreased prolactin concentrations; the possibility that GSD relaxin secretion is deficiency required needs further study. As oral treatment with MPA did not affect progesterone and prolactin release, it may be useful for studying luteal function in pregnant bitches with suspected hypoluteoidism.

Influence of Progesterone Withdrawal on Pregnancy‐Related Parameters During Post‐Implantation Early Pregnancy Loss

Pharmacologically-induced luteolysis or treatment with an antiprogestin in early post-implantation pregnancy in dogs results in asynchronous death and resorption of conceptuses, indicating variable rates of response of individual conceptuses towards progesterone deficiency. This variability also seems to occur in bitches showing pregnancy failure in response to spontaneous luteal deficiency. In a total of 10 beagle pregnancies (two consecutive pregnancies of five bitches), abortifacient treatments beginning on day 24 after ovulation (ov) involved either administration of a progestin antagonist (total of six pregnancies, in three bitches) or a luteolytic regimen of prostaglandin F(2alpha)-analogue together with a dopamine agonist (total of four pregnancies, in two bitches). The outcomes were evaluated in relation to four control pregnancies in two bitches by assay of serum progesterone, prolactin and relaxin at selected time points or within selected time periods, by ultrasound of conceptuses including measurement of uterine blood flow, and parameters of the blood fibrinolytic system including plasma fibrinogen and plasminogen. The process of embryonic death and conceptus resorption was variable in onset and duration both in bitches that received the progesterone antagonist aglepristone (AGLE) and in those under the luteolytic treatment (cloprostenol combined with cabergoline). Pregnancy termination (death of all embryos or foetuses, respectively) occurred as early as day 29 and as late as day 41 after ov in AGLE-treated bitches, and not earlier than day 37 after ov in luteolytic-treatment bitches. Impending embryonic death was not predicted by changes in relaxin concentration, parameters of the fibrinolytic system, or in the perfusion of small uteroplacental vessels.

Circulating relaxin and cervical length in midpregnancy are independently associated with spontaneous preterm birth

We sought to examine associations among serum relaxin levels, cervical length, and spontaneous preterm birth (sPTB). We conducted a case-control study within a cohort of 1080 singleton pregnant women. In all, 38 women (3.5%) delivered spontaneously preterm (< 37 completed weeks of gestation). Relaxin was measured in serum in gestational weeks 12 and 19, cervical length only in week 19. Associations to sPTB were evaluated by logistic regression analysis and receiver operating characteristic curves. Cervical length and relaxin in week 19, but not week 12 were associated to sPTB. There were no correlations between cervical length and relaxin level in week 12 (controls: Spearman rho: -0.07, P = .45; cases: Spearman rho: -0.07, P = .72) or week 19 (controls: Spearman rho: -0.03, P = .77; cases: Spearman rho: 0.04, P = .84). There were no correlation between relaxin concentrations and the cervical length, indicating that relaxin is probably not the cause of preterm shortening of the cervix.

Relaxin Concentrations in Serum and Urine of Endangered and Crazy Mixed‐Up Species

The human population explosion has pushed many mammalian wildlife species to the brink of extinction. Conservationists are increasingly turning to captive breeding as a means of preserving the gene pool. We previously reported that serum immunoactive relaxin provided a reliable means of distinguishing between true and pseudopregnancy in domestic dogs, and this method has since been found to be a reliable indicator of true pregnancy in endangered Asian and African elephants and Sumatran rhinoceroses. Our canine relaxin radioimmunoassay (RIA) has now been adapted and validated to measure relaxin in the serum and urine of felids, including domestic and wild species. Moreover, a commercially available canine serum relaxin kit (Witness) Relaxin Kit; Synbiotics, San Diego, CA), has been adapted for reliable detection of relaxin in urine of some felid species. Our porcine relaxin RIA has also been utilized to investigate the role of relaxin in reproductive processes of the spotted hyena, a species in which the female fetuses are severely masculinized in utero. Indeed, this species might well now be extinct were it not for the timely secretion of relaxin to enable copulation and birth of young through the clitoris. Additional studies have suggested relaxin may be a useful marker of pregnancy in the northern fur seal and the maned wolf (the former species has been designated as "depleted" and the latter as "near threatened"). Given appropriate immunoassay reagents, relaxin determination in body fluids thus provides a powerful tool for conservationists and biologists investigating reproduction in a wide variety of endangered and exotic species.

Circulating levels of relaxin and its relation to cardiovascular function in patients with hypertension

Background. The role of endogenous relaxin on hypertensive cardiovascular damage remains unknown. We investigated the relaxin level and its relation to cardiovascular function in patients with never treated hypertension (HT). Methods. We studied 42 (47.8±10 years) never treated patients with HT and 40 age‐matched (47±8.6 years) normotensive individuals. Serum relaxin levels were determined in all subjects using enzyme‐linked immunosorbent assay. Left ventricular (LV) diameters were evaluated by transthoracic echocardiography. Ejection fraction and LV mass index were measured. Diastolic functions were evaluated with both conventional and tissue Doppler echocardiography. We evaluated central aortic pressures, heart rate‐corrected augmentation index (AIx@75), a marker of wave reflections, and aortic pulse wave velocity (PWV) as indices of elastic‐type aortic stiffness of the study population using applanation tonometry (SphygmoCor). Results. Relaxin levels were significantly lower in hypertensive patients as compared with controls (36.5±7.3 vs 49.7±39.8 pg/ml, p=0.03). The relaxin level was negatively correlated with brachial and central aortic pressure. However, serum relaxin was not significantly associated with LV diameters, ejection fraction, LV mass index, LV diastolic function, AIx@75 or aortic PWV in our study. Conclusion. Serum relaxin is decreased in patients with HT. However, low endogenous relaxin is not related to cardiovascular function.

166 POTENTIAL OF URINARY RELAXIN AS A USEFUL INDICATOR OF PREGNANCY IN THE MANED WOLF

The maned wolf (Chrysocyon brachyurus), a neotropical canid, lives in habitats severely compromised by agricultural development. Therefore, maintaining a healthy and viable zoo population is crucial, because it serves as hedge against extinction. However, the North American ex situ population of maned wolves is far from self-sustaining, mainly due to low pregnancy success and high neonatal mortality. Currently, there is no non-invasive way to determine pregnancy in this species. Therefore, the goal is to determine whether urinary relaxin can be used as an indicator of pregnancy in this species. Objectives were to (1) determine the relationship between serum and urinary relaxin in canids, using pregnant domestic bitches as a model, and (2) evaluate the patterns of urinary relaxin in pregnant v. non-pregnant female maned wolves. Serum and urine samples were obtained weekly from six pregnant domestic bitches starting from the day of natural breeding until 3 weeks before the estimated whelping dates. For the maned wolf, urine and feces were obtained weekly during a breeding season (October to February) from six females, three of which were pregnant and gave birth. Concentrations of serum and urinary relaxin were measured using the double antibody canine relaxin radioimmunoassay (Steinetz et al. 1996 Biol. Reprod. 54, 1252–1260). Fecal progestagen were determined using an enzyme immunoassay (Songsasen et al. 2006 Theriogenology 66, 1743–1750). The relationship between serum and urinary relaxin concentrations was determined using the Pearson Product Moment Correlation Analysis. The relationship between urinary relaxin concentrations and days before whelping (for pregnant females) or time after the initial rise of progestagen for each individual were determined using a linear regression analysis. Serial dilutions of pooled dog urine produced displacement curves parallel to those of the appropriate synthetic canine relaxin standards, while wolf samples showed limited parallelism with low concentration of immunoactive antigen. Concentrations of urinary relaxin were significantly correlated with the serum counterpart in pregnant dogs (P &lt; 0.01, r2 0.58). In pregnant maned wolves, relaxin level increased two- to six-fold as gestation progressed (P &lt; 0.05, r2 ranged from 0.15 to 0.56). In contrast, urinary relaxin remained at the baseline in non-pregnant females throughout the diestrus period (P &gt; 0.05). In conclusion, our findings suggest that urinary relaxin mirrors serum relaxin during pregnancy in domestic bitches and may have potential as a tool to diagnose pregnancy in the maned wolf. Further studies are required to improve the specificity and sensitivity of this non-invasive assay.

Cervix Length and Relaxin as Predictors of Preterm Birth

BackgroundMeasurement of mid-gestation cervix length has become a common screening tool for preterm birth. Our study was designed to assess the value of cervix length and serum relaxin in the prediction of spontaneous preterm birth at < 35 and < 37weeks’ gestation in a general obstetric population. MethodsA prospective cohort of women with a singleton pregnancy had blood collected at 24 and 28weeks’ gestation for determination of serum relaxin immediately before transvaginal ultrasound measurement of cervical length. Patients and referring physicians were blinded to cervix length and relaxin levels to preclude changes in management. The primary outcomes were spontaneous delivery at < 35 and < 37weeks’ gestation. ResultsA total of 1004 women entered the study. Delivery data were not available for 20 women who delivered elsewhere. Twenty women were excluded because preterm delivery was undertaken because of pregnancy abnormalities. Of the 964 women with known gestational age at delivery, 46 (4.8%) delivered at < 37weeks and 16 (1.7%) at < 35weeks’ gestation. Mean cervix length at 28weeks (36.7 ± 7.3mm) was significantly shorter than at 24weeks (37.8 ± 7.1mm) (P < 0.001). Cervix length at 24 and 28weeks’ gestation was equally predictive of preterm birth. A cervix length of ≤030mm at 28weeks had a sensitivity of 57.1%, a specificity of 81.8%, and a positive predictive value of 4.5% for birth at < 35weeks. Serum relaxin levels were not correlated with cervix length at either 24 or 28weeks. Serum relaxin at 24 and 28weeks’ gestation was not associated with preterm birth before or after controlling for patient characteristics and cervix length. ConclusionSerum relaxin levels at 24 and 28weeks’ gestation are not associated with preterm birth. Although cervix length is associated with preterm birth, its positive predictive value is low. Given the lack of proven therapies for those at risk, cervix length does not appear to be a useful screening tool for preterm delivery in the general obstetric population.

Mid‐trimester serum relaxin concentrations and post‐partum pelvic floor dysfunction

To compare mid-trimester serum relaxin concentration (SRC) in primiparous women with or without pelvic floor dysfunction (PFD--stress urinary incontinence (SUI), genital prolapse). Nested observational cohort study. Urogynecology clinic of affiliated University hospital. Primiparous women one to four years post-partum, who had, at time of index pregnancy, participated in a prospective observational study looking at mid-trimester serum relaxin and preterm delivery. Relaxin had been obtained during the index pregnancy at 24 and 28 weeks. Primiparous women who had not given birth to a subsequent child were contacted and asked to return for a single visit assessing pelvic floor function. Pelvic Organ Prolapse Quantification system (POPQ) and Urogenital Distress Inventory (UDI-6). Fifty women participated, of whom 40 delivered vaginally. Seventeen (34%) women had prolapse and 23 (46%) had stress incontinence. Relaxin was slightly higher (not significantly) in women with PFD than in those without. Relaxin concentration declined significantly more rapidly from 24 to 28 weeks in incontinent women, after adjusting for baseline and obstetrical factors. In contrast to previous reports, mid-gestation relaxin tended to be higher and fall significantly faster in women with PFD. Acknowledging relaxin's effects on collagen turnover, our findings explore the association between childbirth and PFD.

Relaxin Promotes Prostate Cancer Progression

To understand the role of relaxin peptide in prostate cancer, we analyzed the expression of relaxin and its receptor in human prostate cancer samples, the effects of relaxin signaling on cancer cell phenotype in vitro, and the effects of increased serum relaxin concentrations on cancer progression in vivo. The relaxin and its receptor leucine-rich repeat containing G protein-coupled receptor 7 (LGR7) expression were studied by quantitative reverse transcription-PCR (11 benign and 44 cancer tissue samples) and by relaxin immunohistochemistry using tissue microarrays containing 10 normal and 69 cancer samples. The effects of relaxin treatment and endogenous relaxin/LGR7 suppression via short interfering RNA in PC-3 and LNCaP cells were analyzed in vitro. The effect of transgenic relaxin overexpression [Tg(Rln1)] on cancer growth and survival was evaluated in autochthonous transgenic adenocarcinoma of the mouse prostate (TRAMP). The relaxin mRNA expression was significantly higher in recurrent prostate cancer samples. In tissue microarrays of the 10 normal tissues, 8 had low staining in epithelial cells, whereas only 1 of 9 high-grade prostatic intraepithelial neoplasia lesions had low expression (P = 0.005) and only 29 of 65 cancers had low expression (P = 0.047). Stimulation with relaxin increased cell proliferation, invasiveness, and adhesion in vitro. The suppression of relaxin/LGR7 via short interfering RNAs decreased cell invasiveness by 90% to 95% and growth by 10% to 25% and increased cell apoptosis 0.6 to 2.2 times. The Tg(Rln1) TRAMP males had shorter median survival time, associated with the decreased apoptosis of tumor cells, compared with non-Tg(Rln1) TRAMP animals. Relaxin signaling plays a role in prostate cancer progression.

Pregnancy Diagnosis in Cats Using a Rapid, Bench‐top Kit to Detect Relaxin in Urine

Relaxin is a pregnancy-specific hormone in the queen and is produced by the placenta. Both serum and urinary relaxin levels can be used to diagnose and monitor pregnancy in the cat; however, only serum levels are commonly measured in practice. The present study aimed to assess whether urine could be used for the rapid diagnosis of pregnancy at an early stage in domestic cats using a bench-top kit to detect relaxin. Paired serum and urine samples were collected during the first month of gestation in six cats. The samples were tested by applying neat serum, urine or urine diluted in non-pregnant cat serum to the Witness Relaxin kit. Relaxin concentrations in the paired samples were also measured by radioimmunoassay. All undiluted urine samples from pregnant cats tested negative using the bench-top kit; however, the kit was able to detect relaxin in urine after dilution with non-pregnant cat serum. Using this as the test sample, the kit was accurate at diagnosing pregnancy from 28 days after mating and some samples tested positive at 21 days after mating. This preliminary work could lead to the development of a home pregnancy test for cats.

O-264: Response to superovulation does not predict preterm delivery in pregnancies resulting from A.R.T

Ovarian stimulation by exogenous gonadotropins resulting in the formation of multiple corpus lutei is expected to increase serum relaxin, a peptide hormone and potent stimulator of collagen breakdown. Elevated relaxin levels are associated with preterm delivery in both singleton and multiple gestations (Weiss et al., 1993; Iams et al., 2001). Therefore, our objective was to assess whether an association exists between oocyte numbers at retrieval and preterm delivery in pregnancies resulting from ART.

Early mid-trimester serum relaxin, soluble CD163, and cervical length in women at high risk for preterm delivery

The purpose of this study was to evaluate the relationship between serum concentrations of relaxin and soluble CD163 with cervical length and preterm delivery in women with previous spontaneous preterm delivery. Sixty-one of 69 pregnant women with a previous spontaneous preterm had serum relaxin and soluble CD163 measured at week 16 (range, 12-25 weeks). End points were cervical length and gestational age at delivery. Of the 61 women, 26% had >1 previous spontaneous preterm delivery; 84% were black; 87% were unmarried; 13% were smokers, and 39% were delivered before 37 weeks of gestation. Neither relaxin (median, 368 ng/L; range, 83-1493 ng/L) nor soluble CD163 (2.4 mg/L; range, 0.86-6.85 mg/L) correlated with cervical length or gestational age at delivery. Black women had higher relaxin levels (436 vs 205 ng/L; P = .002), but soluble CD163 levels were similar among racial groups. Relaxin and soluble CD163 measured at 16 weeks of gestation are not clinically useful predictors of short cervical length or preterm delivery in women with a previous spontaneous preterm delivery.

Relaxin and β-estradiol modulate targeted matrix degradation in specific synovial joint fibrocartilages: progesterone prevents matrix loss

Relaxin, a 6-kDa polypeptide hormone, is a potent mediator of matrix turnover and contributes to the loss of collagen and glycosaminoglycans (GAGs) from reproductive tissues, including the fibrocartilaginous pubic symphysis of several species. This effect is often potentiated by β-estradiol. We postulated that relaxin and β-estradiol might similarly contribute to the enhanced degradation of matrices in fibrocartilaginous tissues from synovial joints, which may help explain the preponderance of diseases of specific fibrocartilaginous joints in women of reproductive age. The objective of this study was to compare the in vivo effects of relaxin, β-estradiol, and progesterone alone or in various combinations on GAG and collagen content of the rabbit temporomandibular joint (TMJ) disc fibrocartilage, knee meniscus fibrocartilage, knee articular cartilage, and the pubic symphysis. Sham-operated or ovariectomized female rabbits were administered β-estradiol (20 ng/kg body weight), progesterone (5 mg/kg), or saline intramuscularly. This was repeated 2 days later and followed by subcutaneous implantation of osmotic pumps containing relaxin (23.3 μg/kg) or saline. Tissues were retrieved 4 days later and analyzed for GAG and collagen. Serum relaxin levels were assayed using enzyme-linked immunosorbent assay. Relaxin administration resulted in a 30-fold significant (p < 0.0001) increase in median levels (range, approximately 38 to 58 pg/ml) of systemic relaxin. β-estradiol, relaxin, or β-estradiol + relaxin caused a significant loss of GAGs and collagen from the pubic symphysis and TMJ disc and of collagen from articular cartilage but not from the knee meniscus. Progesterone prevented relaxin- or β-estradiol-mediated loss of these molecules. The loss of GAGs and collagen caused by β-estradiol, relaxin, or β-estradiol + relaxin varied between tissues and was most prominent in pubic symphysis and TMJ disc fibrocartilages. The findings suggest that this targeted modulation of matrix loss by hormones may contribute selectively to degeneration of specific synovial joints.

Prediction of preterm delivery using changes in serum relaxin in low risk pregnancies

Objective To examine serum relaxin as a predictor of spontaneous preterm delivery. Study design A prospective study of 2846 women with singleton pregnancies, from which a matched case–control study (84 cases of spontaneous preterm delivery before 37 weeks gestation and 175 controls) and a cohort (84 preterm and 399 term deliveries) were extracted. Results In the women with a subsequent preterm delivery the relaxin level decreased by 0.9% per week as compared to 1.9% per week ( t-test, p = 0.004) in the women with term deliveries. From the cohort the course of S-relaxin during pregnancy in both preterm and term deliveries were fitted and graphed. S-relaxin level was raised in women who were hormonally stimulated to obtain pregnancy ( p = 0.0001), and lower in women with pre-pregnancy overweight (BMI ≥ 25, p = 0.01) as well as in women, who had previously been pregnant ( p = 0.008). A longitudinal adjusted model for the prediction of preterm delivery based on the change in S-relaxin was established. Conclusions S-relaxin levels decrease less rapidly in women who subsequently deliver preterm; this results in elevated S-relaxin levels in the second and the third trimesters.

Biomarkers for the prediction of preterm delivery

This structured review discusses the current literature on selected biomarkers and their ability to predict preterm delivery (PTD). Among symptomatic women, the likelihood ratio (LR+) for the prediction of PTD was found to be greater than 10 using amniotic fluid (AF) interleukin-6 (IL-6), AF Ureaplasma urealyticum, as well as a multi-marker consisting of cervical IL-6, cervical IL-8, and cervical length (CL). The LR+ was found to be between 5 and 10 for serum C-reactive protein (CRP). An LR+ between 2.5 and 5 was recorded for serum corticotropin-releasing hormone (CRH), cervical fetal fibronectin (fFN), cervical IL-6, serum relaxin, and a multi-marker consisting of fFN and CL. CL and bacterial vaginosis (BV) both predicted PTD in women with preterm labor with an LR+ of less than 2.5. In asymptomatic women, AF U. urealyticum and a multimarker consisting of five individual markers [fFN, CL, serum alpha-fetoprotein (AFP), serum alkaline phosphatase, and serum granulocyte colony-stimulating factor (G-CSF)] predicted PTD with an LR+ greater than 10. The LR+ was between 5 and 10 for serum relaxin and CL. LRs+ recorded for serum alkaline phosphatase, salivary estriol, serum CRH, serum G-CSF, cervical IL-6, AF IL-6, cervical fFN, AFP, and Chlamydia all ranged between 2.5 and 5. Finally, an LR+ below 2.5 has been documented for serum ferritin, serum CRP, BV, and cervical ferritin.

Renal Hemodynamic Effects of Relaxin in Humans

Rat studies have convincingly demonstrated the essential role of the ovarian hormone relaxin in mediating gestational renal hemodynamic and osmoregulatory changes in that species. We describe a model in nonpregnant volunteers using exogenous hCG to stimulate the production and release of ovarian relaxin in order to assess renal hemodynamic responses. Women (n = 10) were serially studied +/- hCG stimulation during menstrual cycles with measurement of inulin, PAH, and neutral dextran clearances (to determine glomerular filtration rate [GFR], renal plasma flow [RPF], and glomerular porosity, respectively). Controls were women without ovarian function (n = 6) and men (n = 10). GFR and RPF were increased in the luteal phase compared to the follicular phase (15.3% increase in GFR, P < 0.005; 17.8% increase in RPF, P < 0.05). In controls, GFR and RPF were not significantly different between study occasions. Although exogenous hCG did not stimulate relaxin secretion in women without ovarian function or in men, it did so in normal women, but not into the pregnancy range. In no group were renal hemodynamics augmented by administered hCG. In naturally occurring cycles, increased serum relaxin is associated with augmented renal hemodynamics. As luteal stimulation with hCG failed to yield pregnancy relaxin levels, the use of exogenous relaxin for human administration is needed to further elucidate the renal vasodilatory properties of relaxin.

Relaxin Concentrations in Serum and Urine of Endangered Species: Correlations with Physiologic Events and Use As a Marker of Pregnancy

Many mammalian species are facing extinction due to problems created by human encroachment, agriculture, pollution, and willful slaughter. Among those at risk are the Asian and African elephant, Sumatran rhinoceros, and giant panda. Conservation groups try to save species in the wild by preserving habitat and limiting animal-human conflicts, often with limited success. Another alternative is to preserve the extant gene pool through captive breeding as a hedge against extinction. Measurement of circulating reproductive hormones is impractical for most wildlife species; determination of urinary or fecal hormone metabolites provides a more viable approach. To aid breeding management, one important tool is the ability to diagnose and monitor pregnancy, especially in species with long gestations (e.g., rhinos over 15 mo and elephants over 20 mo). Unfortunately, measuring progestins often is not useful diagnostically, because concentrations are similar during at least part of the pregnancy and the nonpregnant luteal phase in some species (e.g., elephants, rhinoceroses, and giant pandas). As serum relaxin reliably distinguishes between pregnancy and pseudopregnancy in bitches, relaxin measurement might also provide a method for detecting a successful pregnancy in endangered species. Appropriate immunoassay reagents have enabled the estimation of relaxin concentrations in the serum of elephants and rhinos and the determination of pregnancy establishment and the outcome. Relaxin was also detected in panda serum and urine. However, the extreme variability of the time between observed mating and parturition and the confounding factors of delayed implantation, pseudopregnancy, and frequent fetal resorptions made it impossible to use the panda relaxin data as a specific marker of pregnancy.

Serum relaxin, soluble CD163 levels and cervical length in women at high risk for preterm birth

Serum relaxin, the inflammatory marker soluble CD163, bacterial vaginosis (BV), and short cervical length (CL) have all been associated with spontaneous preterm birth (SPTB). We sought to evaluate the relationship between these risk factors and SPTB in a group of women at high risk for SPTB.

Elevated concentrations of serum relaxin are associated with metastatic disease in breast cancer patients.

Relaxin (RLX) is known to induce remodeling of benign stromal tissues through upregulation of matrix metalloproteases (MMPs). Recently, we could show that RLX also induces MMPs in breast cancer cells and enhances in vitro invasiveness. To investigate its potential role for progression of breast cancer in vivo, RLX serum concentrations were determined in 160 breast cancer patients during post-surgical follow-up. RLX concentrations in cancer patients were significantly higher than in a control population of healthy blood donors and patients with various other diseases (0.47 versus 0.29 ng/ml, p < 0.0001). There was a significant difference between patients with metastases (0.62 ng/ml) and those without (0.38 ng/ml, p < 0.0001). Overall survival was shorter in RLX-positive ( > 0.4 ng/ml) than in RLX-negative patients (p = 0.016). Cox regression analysis showed that RLX was not an independent variable, in contrast to metastatic disease and primary lymph node involvement. Taken together, the detection of elevated RLX concentrations especially in patients with metastases supports the assumption that there is a role for RLX in tissue remodeling during breast cancer progression.