Relaxin Concentrations Research Articles

Potential Binding Sites for Relaxin in Pregnant Rabbits

The purpose of this study was to identify tissues in the day 25 pregnant rabbit that bind relaxin. First, the clearance half-life of relaxin from the rabbit (n = 6) was determined by injecting 10 g porcine relaxin via the marginal ear vein. One-milliliter blood samples were collected via a cannula in the central ear artery. Samples were collected at 10- and 5-min pre-relaxin and at 1-min intervals post-relaxin injection, and the relaxin concentrations determined by radioimmunoassay. The clearance half-life was 4 min. Next, pregnant rabbits were infused with [125I]-relaxin. Control rabbits (n = 3) received 10 g radio-inert relaxin via the marginal ear vein in order to saturate endogenous receptors. Ten minutes later, 10 ng [125I]-relaxin was similarly injected. Treated rabbits (n = 3) received only [125I]-relaxin. After allowing sufficient time for clearance (24 min), a 1-mL blood sample was removed via the central ear vein. Rabbits were euthanized, tissues of maternal and fetal origin excised, and cpm/mg of tissue divided by cpm/mL of blood was determined. Differences in uptake of [125I]-relaxin between control and treated animals, using the Student paired t test, were found for the uterus (P < .05), uterine cervix (P < .03), and mammary gland (P < .05). These data suggest potential rabbit tissues with the LGR-7 receptor.

Relaxin Stimulates Protein Kinase C ζ Translocation: Requirement for Cyclic Adenosine 3′,5′-Monophosphate Production

Relaxin is a polypeptide hormone that activates the leucine-rich repeat containing G protein-coupled receptors, LGR7 and LGR8. In an earlier study, we reported that relaxin produces a biphasic time course and the second wave of cAMP is highly sensitive to phosphoinositide-3 kinase inhibitors (LY294002 and wortmannin). LY294002 inhibits relaxin-mediated increases in cAMP production by 40-50% across a large range of relaxin concentrations. Here we show that protein kinase C zeta (PKCzeta) is a component of relaxin signaling in THP-1 cells. Sphingomyelinase increases cAMP production due to the release of ceramide, a direct activator of PKCzeta. Chelerythrine chloride (a general PKC inhibitor) inhibits relaxin induced cAMP production to the same degree (approximately 40%) as LY294002. Relaxin stimulates PKCzeta translocation to the plasma membrane in THP-1, MCF-7, pregnant human myometrial 1-31, and mouse mesangial cells, as shown by immunocytochemistry. PKCzeta translocation is phosphoinositide-3 kinase dependent and independent of cAMP production. Antisense PKCzeta oligodeoxynucleotides (PKCzeta-ODNs) deplete both PKCzeta transcript and protein levels in THP-1 cells. PKCzeta-ODNs abolish relaxin-mediated PKCzeta translocation and inhibit relaxin stimulation of cAMP by 40%, as compared with mock and random ODN controls. Treatment with LY294002 in the presence of PKCzeta-ODNs results in little further inhibition. In summary, we present a novel role for PKCzeta in relaxin-mediated stimulation of cAMP.

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.

Relaxin is an independent risk factor predicting death in male patients with end-stage kidney disease.

Patients with end-stage kidney disease (ESKD) have a reduced life expectancy mainly as the result of cardiovascular diseases. Relaxin has been implicated in the pathogenesis of cardiovascular diseases. We analyzed the impact of relaxin on death in patients with ESKD. Patients (n =245; 122 women, 123 men) on long-term hemodialysis were followed for 1140 days for death. Blood samples for analysis of relaxin, C-reactive protein, Troponin T, cholesterol, HDL, brain natriuretic peptide, and albumin were taken at study entry. Survival was compared by the Kaplan-Meier method and Cox regression analysis. One hundred seven patients died during the observation period; 66 died of cardiovascular diseases and 28 died of infectious diseases. Elevated serum relaxin concentrations (greater than median) predicted death in male but not in female patients with ESKD: All-cause death (men: relative risk, 2.63; 95% CI, 1.34 to 5.12; P=0.005; women: relative risk, 0.671; 95% CI, 0.33 to 1.35; P=0.262) and cardiovascular death (men: relative risk, 2.95; 95% CI, 1.20 to 7.21; P=0.018; women: relative risk, 0.639; 95% CI, 0.26 to 1.56; P=0.324). Relaxin is an independent risk factor predicting death in male patients with ESKD on chronic hemodialysis.

Non-Oral Poster 80: Second Trimester Serum Relaxin Concentrations are Associated with Pelvic Organ Prolapse Following Childbirth

Non-Oral Presentations: AUGS-SGS Abstracts: 2004 Joint Scientific Meeting The American Urogynecologic Society and The Society of Gynecologic Surgeons

Endocrine and ultrasonographic characterization of a successful pregnancy in a Sumatran rhinoceros (Dicerorhinus sumatrensis) supplemented with a synthetic progestin

AbstractA Sumatran rhinoceros with a history of early pregnancy loss was supplemented with a synthetic progestin, altrenogest (Regu‐Mate®), and delivered a healthy, full‐term calf 475 days after mating. Serum hormone concentrations were measured throughout gestation, and ultrasonography was used to monitor embryo/fetal growth and viability. The embryonic vesicle growth curve was characterized by three phases: rapid expansion, plateau, and a final rapid expansion, and was similar to that in the domestic horse. Fetal sex was determined by ultrasound on day 73 of gestation. After day 80 of gestation, transabdominal examinations were more useful than rectal examinations for imaging the fetus. Serum progesterone concentrations remained at luteal levels (1.5±0.5 ng/ml) for the first 2 months of pregnancy, and then they gradually increased. However, progesterone decreased almost to luteal levels during the fifth month before it increased again, and eventually reached peak concentrations (13.3±1.9 ng/ml) shortly before parturition. Relaxin concentrations remained basal (≤0.5 ng/ml) for the first half of the pregnancy, increased to 2.7±1.2 ng/ml and stabilized until 2 weeks before parturition, when relaxin spiked to unusually high concentrations (800–1300 ng/ml). Prolactin concentrations were at baseline (7.2±1.7 ng/ml) throughout most of the gestation, but rose markedly 2 weeks before parturition, reaching concentrations as high as 75 ng/ml. Attempts to measure serum estrogen concentrations were unsuccessful. These data represent the first attempt to characterize pregnancy in the critically endangered Sumatran rhinoceros, a species that heretofore had not successfully reproduced in captivity for 112 years. Zoo Biol 23:219–238, 2004. © 2004 Wiley‐Liss, Inc.

Hormonal and behavioural changes during the mating season and pregnancy in Alpine marmots (Marmota marmota)

Under natural and artificial conditions, Alpine marmots (Marmota marmota) are true hibernators with a single breeding season starting immediately upon emergence from hibernation. Over three mating and breeding seasons, hormonal and mating patterns of colony-housed reproductive female marmots were investigated after exit from hibernation. Blood samples were taken for progesterone, oestrogen and relaxin assays with parallel ultrasound investigations. Copulations were observed from the first day after exit from hibernation until the end of pregnancy and reached a maximum number on day 37 before parturition. Mating behaviour was observed between the dominant animals as well as between dominant and subdominant group members. In the first week after exit from hibernation, plasma progesterone was detected in half of the animals. During the third week, progesterone concentrations were significantly higher in pregnant than in non-pregnant animals or animals that had aborted. Immediately after emerging from hibernation, all successfully mated females showed higher serum relaxin values than non-successfully mated animals and this increase in relaxin concentration lasted until the end of pregnancy. The total concentration of oestrogen did not differ between pregnant and non-pregnant animals. The results of this study indicate that progesterone and relaxin might be useful indicators of early pregnancy in Alpine marmots.

Hormonal and behavioural changes during the mating season and pregnancy in Alpine marmots (Marmota marmota).

Under natural and artificial conditions, Alpine marmots (Marmota marmota) are true hibernators with a single breeding season starting immediately upon emergence from hibernation. Over three mating and breeding seasons, hormonal and mating patterns of colony-housed reproductive female marmots were investigated after exit from hibernation. Blood samples were taken for progesterone, oestrogen and relaxin assays with parallel ultrasound investigations. Copulations were observed from the first day after exit from hibernation until the end of pregnancy and reached a maximum number on day 37 before parturition. Mating behaviour was observed between the dominant animals as well as between dominant and subdominant group members. In the first week after exit from hibernation, plasma progesterone was detected in half of the animals. During the third week, progesterone concentrations were significantly higher in pregnant than in non-pregnant animals or animals that had aborted. Immediately after emerging from hibernation, all successfully mated females showed higher serum relaxin values than non-successfully mated animals and this increase in relaxin concentration lasted until the end of pregnancy. The total concentration of oestrogen did not differ between pregnant and non-pregnant animals. The results of this study indicate that progesterone and relaxin might be useful indicators of early pregnancy in Alpine marmots.

Inhibition of markers of hepatic stellate cell activation by the hormone relaxin

Hepatic fibrosis results from excess extracellular matrix produced primarily by hepatic stellate cells (HSC). In response to injury, HSC differentiate to a myofibroblastic phenotype expressing smooth muscle actin and fibrillar collagens. Relaxin is a polypeptide hormone shown to have antifibrotic effects in fibrosis models. In this study, activated HSC from rat liver were treated with relaxin to determine if relaxin can reverse markers of HSC activation. Relaxin treatment resulted in a decrease in the expression of smooth muscle actin, but had no effect on cell proliferation rate. The levels of total collagen and type I collagen were reduced, while the synthesis of new collagen was inhibited. Furthermore, relaxin caused an increase in the expression and secretion of rodent interstitial collagenase (MMP-13), but there was no effect on the gelatinases MMP-2 or MMP-9. Relaxin also increased secretion of TIMP-1 and TIMP-2. The effective concentration of relaxin to induce these effects was consistent with action through the relaxin receptor. In conclusion, relaxin reversed markers of the activated phenotype of HSC including the production of fibrillar collagen. At the same time, the activity of a fibrillar collagenase was increased. These data suggest that relaxin not only inhibits HSC properties that contribute to the progression of hepatic fibrosis, but also promotes the clearance of fibrillar collagen. Therefore, relaxin may be a useful approach in the treatment of hepatic fibrosis.

Serum relaxin concentrations and reproduction in male bonnethead sharks, Sphyrna tiburo

Relaxin is a 6-kd polypeptide hormone that is responsible for regulating several reproductive processes in female vertebrates, but its role in male reproduction remains unclear. To aid in clarifying this role, the objective of the present study was to investigate changes in endogenous relaxin levels associated with reproductive events in male elasmobranchs, which represent one of only three vertebrate groups known to possess this hormone. Serum relaxin concentrations were measured in 27 immature and 66 mature male bonnethead sharks ( Sphyrna tiburo), a species with a well-characterized, seasonal reproductive cycle. Temporal changes in serum relaxin concentrations of immature male S. tiburo were not observed. In contrast, a temporal cycle in serum relaxin concentrations of mature male S. tiburo was observed in individuals from two sampling locations. Significant increases ( P<0.05) in serum relaxin concentrations of mature male S. tiburo from both collection sites occurred during late spermatogenesis and the mating period, two critical stages of the reproductive cycle. The results from this study suggest that relaxin may play an important role in regulating semen quality, or other aspects of reproduction in male sharks. This is the first study to demonstrate a temporal pattern in endogenous serum Rlx concentrations associated with reproductive events in feral vertebrates. As such, it strengthens earlier hypotheses that suggested a role for this hormone in regulating male vertebrate fertility and copulatory success.

Seminal immunoreactive relaxin in domestic animals and its relationship to sperm motility as a possible index for predicting the fertilizing ability of sires.

Although immunoassayable relaxin has been detected in human and boar seminal plasma, there is no evidence suggesting the existence of immunoreactive relaxin in the seminal plasma of other domestic animals. The first objective of this study was to determine whether immunoreactive relaxin was present in the seminal plasma of bulls, rams and he-goats. In addition, the correlation of immunoreactive relaxin with sperm motility as an index for predicting the fertilizing ability of bull sires was investigated. Semen with normal sperm motility was collected from bulls, rams and he-goats, and the relaxin immunoreactivity of the semen samples was measured using a time-resolved fluoroimmunoassay (TR-FIA) for porcine relaxin that we developed. The presence of relaxin immunoreactivity was demonstrated in seminal plasma from bulls, rams and he-goats. The level of immunoreactive relaxin in seminal plasma was the highest in bulls followed by humans, rams, boars and he-goats in that order, when relaxin levels in boar and human semen having normal sperm motility were also assayed under the same conditions. When the correlation between the seminal plasma level of immunoreactive relaxin and sperm motility was examined in bull semen samples as an index for predicting fertilizing ability, it was found that the relaxin level was significantly correlated with the percentage of spermatozoa showing the most intensive motility (r = 0.64, p < 0.05). These results indicate that immunoreactive relaxin is widely found in the seminal plasma of domestic animals and that measuring the relaxin concentration of seminal plasma may be useful to identify subfertile sires or predict the fertility potential of individual sires.

Measurement of plasma and tissue relaxin concentrations in the pregnant hamster and fetus using a homologous radioimmunoassay.

A homologous hamster relaxin RIA was developed to evaluate plasma and tissue concentrations of relaxin in the latter half of pregnancy in this species. Relaxin protein and mRNA were localized using antibodies developed to synthetic hamster relaxin and gene-specific molecular probes, respectively. Molecular weight and isoelectric point of the synthetic and native hormones were identical by electrophoretic methods, and synthetic hamster relaxin was active in the mouse interpubic ligament bioassay. Synthetic hormone was used as tracer and standard with rabbit antiserum to the synthetic hormone in the RIA. Relaxin was assayed in blood samples recovered from the retro-orbital plexus on Days 6, 8, 10, 12, 14, 15, and 16 of gestation and on Days 1 and 5 postpartum. Relaxin was first detected on Day 8 of gestation (3.7 +/- 0.6 ng/ml), increased to reach a maximum in the evening of Day 15 (826.0 +/- 124.0 ng/ml), and decreased by Day 16 (day of parturition). Relaxin concentrations were assayed in aqueous extracts of implantation sites (Days 6, 8, and 10) and chorioallantoic placentae (Days 12, 14, and 15). Concentrations were low on Day 6 (0.02 +/- 0.001 microg/g tissue), increased to Day 15 (6.96 +/- 0.86 microg/g tissue), and subsequently declined by the evening of Day 15. Relaxin protein and mRNA were localized to primary and secondary giant trophoblast cells in the chorioallantoic placental trophospongium. However, relaxin protein was not localized in ovaries of pregnant animals or oviductal tissues of cycling animals. Significant quantities of relaxin were detected in the serum of fetal hamsters recovered on Day 15.

Effects of Prostaglandin E2 on Ripening of the Cervix and Secretion of Relaxin, Luteinizing Hormone (LH), Estradiol-17.BETA. and Progesterone at Term Pregnancy in the Japanese Monkey (Macaca fuscata fuscata).

Effects of intracervical prostaglandin E2 (PGE 2)-gel treatment on ripening of the cervix at term pregnancy were investigated. Concentrations of relaxin, LH estradiol-17β and progesterone were measured by radioimmunoassays in the maternal peripheral plasma during 48 hours after treatment with PGE2-gel. Treatment with PGE2-gel induced cervical ripening without induction of labor at term. Plasma levels of estradiol-17β increased after administration of PGE2-gel, whereas plasma levels of relaxin, LH and progesterone were unchanged during the period studied. These results suggest that increased levels of estradiol-17 β may be involved in ripening of the cervix without increasing circulating relaxin during the period of PGE2-gel treatment in the Japanese monkey.

Changes in Circulating Relaxin Levels during Pregnancy and Early Lactation in Japanese Monkeys (Macaca fuscata fuscata).

Changes in relaxin concentrations in plasma throughout pregnancy and early lactation up to one month after parturition were characterized in 10 Japanese monkeys by a heterologous radioimmunoassay (RIA) based on the porcine RIA. Plasma levels of LH/monkey chorionic gonadotropin (mCG), estradiol-17β, progesterone and immunoreactive (ir-) inhibin were also monitored for the entire period. Relaxin levels in the plasma were low before conception. An accelerated rise in plasma relaxin levels was found during pregnancy. The first increase was noted during early pregnancy, with a peak (267.5 ± 50.5 pg/ml) at Day 31 ± 2.4 of pregnancy (Day 0= day of LH surge). The second increase was noted just before term with a peak (235.6 ± 37.5 pg/ml). After parturition, relaxin levels in the plasma abruptly declined but were maintained at approximately 100 ng/ml during early lactation. The first rise in plasma relaxin during pregnancy was in parallel with rises of mCG and progesterone, and the second rises was well correlated with those of plasma estradiol-17β ,progesterone and ir-inhibin. These results suggest that the major source of relaxin is corpus luteum and placenta during pregnancy in Japanese monkeys.

The pregnancy hormone relaxin is a player in human heart failure.

Human congestive heart failure is characterized by complex neurohumoral activation associated with the up-regulation of vasoconstricting and salt-retaining mediators and the compensatory rise of counter-regulatory hormones. In the present study, we provide the first evidence that relaxin (RLX), known as a pregnancy hormone, represents a potential compensatory mediator in human heart failure: plasma concentrations of RLX and myocardial expression of the two RLX genes (H1 and H2) correlate with the severity of disease and RLX responds to therapy. The failing human heart is a relevant source of circulating RLX peptides, and myocytes as well as interstitial cells produce RLX. Elevation of ventricular filling pressure up-regulates RLX expression and the hormone acts as a potent inhibitor of endothelin 1, the most powerful vasoconstrictor in heart failure. Furthermore, RLX modulates effects of angiotensin II, another crucial mediator. Our data identify RLX as a new player in human heart failure with potential diagnostic and therapeutic relevance.

Systemic relaxin in pregnant pony mares grazed on endophyte-infected fescue: effects of fluphenazine treatment

Tall fescue is one of the most widely grown forage grasses for horses in the United States. However, it is frequently infected with the endophyte Neotyphodium coenophialum which produces ergot alkaloids that cause severe adverse effects in the pregnant mare. The objectives of this study were to determine the effects of fescue toxicosis and fluphenazine on circulating relaxin in pregnant pony mares and evaluate the usefulness of relaxin as a monitor of treatment efficacy. Twelve mares were maintained on endophyte-infected tall fescue pasture. Group TRT (n = 6), received 25 mg of fluphenazine decanoate (im) on Day 320 of gestation while Group UTRT served as untreated controls. Daily blood samples were collected from Day 300 of gestation until Day 3 post partum and analyzed for plasma relaxin concentrations using a homologous equine radioimmunoassay. Mean gestation lengths were 330 ± 0.7 and 336.5 ± 3.2 days for TRT and UTRT mares, respectively (P = 0.07). Mean plasma relaxin concentrations in both groups of mares during the week before treatment (Day 313 to 319) were not different (UTRT, 53.4 ± 11.3 ng/mL; TRT, 61.4 ± 9.3 ng/mL). In the week after treatment (Day 320 to 326), mean plasma relaxin tended to be higher (P = 0.1) in TRT mares (66.7 ± 6.2 ng/mL) when compared with UTRT mares (49.6 ± 6.6 ng/mL), representing a 17.1 ng/mL difference in circulating relaxin between the two groups. Systemic relaxin during the last week before delivery (days relative to parturition) for UTRT and TRT mares was 45.7 ± 6.7 and 64.7 ± 6.4 ng/mL (P = 0.06), respectively. At Day −8 and Day −5 relative to parturition, systemic relaxin in TRT mares was significantly higher (P < 0.05) than in UTRT mares. Three of the six UTRT mares and one TRT mare showed clinical symptoms of fescue toxicosis. In the week before delivery, circulating relaxin in mares with problematic pregnancies (39.9 ± 7.8 ng/mL) was significantly lower than concentrations measured in mares with normal pregnancies (63.4 ± 5.4 ng/mL; P = 0.03). Clinical observations suggest that a one-time injection with fluphenazine improved pregnancy outcome by reducing the adverse effects of fescue toxicosis concomitant with a stabilization of plasma relaxin concentrations. These data support the hypothesis that systemic relaxin may be a useful biochemical means of monitoring placental function and treatment efficacy in the mare.

Association between raised serum relaxin levels during the eighteenth gestational week and very preterm delivery

Objective: Our aim was to evaluate a possible association between serum relaxin levels in the 18th gestational week and preterm delivery. Study Design: We conducted a nested case-control study that was based on serum samples obtained in the 18th week of gestation from 1545 unselected healthy primiparous women. Eleven case subjects were delivered very early (9 spontaneously, 2 by indicated cesarean delivery) and 42 moderately early (41 spontaneously, 1 by indicated cesarean delivery); 123 control subjects (121 having spontaneous labor, 2 undergoing indicated cesarean delivery) were randomly selected among the women with delivery at term. Results: The serum relaxin concentration during the 18th gestational week was 63% higher among subjects with very preterm deliveries than among control subjects (P =.01, Mann-Whitney test). High relaxin levels during the 18th gestational week were associated with an increased risk of very preterm delivery (odds ratio, 11.3; 95% confidence interval, 2.14-59.1) and spontaneous very preterm delivery (odds ratio, 5.5; 95% confidence interval, 1.3-23). There was a negative correlation for case subjects and control subjects between serum relaxin concentrations during the 18th gestational week and gestational age at delivery (P <.05). Conclusion: Serum relaxin may be an independent predictor when identification of women at risk of very preterm delivery is attempted in the 18th gestational week. (Am J Obstet Gynecol 2001;184:390-3.)

The Presence of Specific Binding Sites on Boar Spermatozoa for Porcine Relaxin and Its Action on Their Motility Characteristics.

The purpose of this investigation was to examine whether boar spermatozoa possess specific binding sites for relaxin and to examine what effects relaxin actually exerts on their motility characteristics. Boar spermatozoa were collected from cauda epididymides. For the relaxin binding study, washed cauda epididymal spermatozoa were smeared on glass slides, and specific sites that bind relaxin were identified by sequential application of a biotinylated relaxin probe, antibiotine immunoglobulin G conjugated to 1 nm colloidal gold, and silver for signal amplification. For the motility characteristics study, cauda epididymal spermatozoa were diluted 300-fold in modified KRB + 2% cauda epididymal fluid (approximately 1 × 10 7 cell/ml). After preincubation for 30 min at 37 C in a CO2 incubator, the sperm aliquots were placed in culture dishes covered with mineral oil and mixed with porcine relaxin. The concentrations of relaxin and spermatozoa in the aliquot were 100 ng/ml and 5 × 106 cells/ml, respectively. The aliquots were incubated for a certain defined period under the same conditions. After 30, 60, 90 and 120 min of incubation, sperm motility was recorded using a videotape recorder. As an evaluation of motility characteristics, the percent motility, grade of forward progression and velocity were examined. The results of the relaxin binding study demonstrated that relaxin bound with specificity to the midpiece and tail. In addition, bindings were visible at the acrosome cap and neck of the head. The results of the motility study which examined the effects of relaxin on the motility characteristics of boar sperm showed that relaxin did not cause a significant alteration in percent motility, but it improved forward progression. Relaxin treatment for 90 min produced a significant 1.4-fold enhancement in sperm velocity compared to that of control. These results suggest that relaxin activates sperm motility through a specific receptor.

Reproductive hormones and blood pressure during pregnancy.

The mechanisms involved in cardiovasular changes during human pregnancy and the complicated aetiology of gestational hypertension are unclear. Reproductive hormones have known effects on the cardiovascular system in the non-pregnant state and in animal systems, but their effects in human pregnancy are uncertain. In this study of pregnant women, the effects of serum concentrations of relaxin, progesterone and oestradiol on arterial blood pressure were studied. Higher serum concentrations of progesterone and relaxin, but not oestradiol, in early pregnancy were related to lower mean systolic blood pressures in the second and third trimesters. No relationship was found between hormonal concentrations and diastolic blood pressures. However, women with a diastolic blood pressure of >90 mmHg in late pregnancy showed statistically significant lower relaxin concentrations in early pregnancy in comparison with women whose diastolic blood pressure was </=90 mmHg. In a multivariate analysis, the mean systolic blood pressure (P: < 0.0001) and serum relaxin (P: < 0.01) in early pregnancy, but not progesterone, were independently related to systolic blood pressure in late pregnancy. The results support previous experimental and clinical studies. The effect of relaxin may be explained by a possible vasodilatatory action seen in animal studies and appears to be moderate.

Reproductive hormones and stress urinary incontinence in pregnancy

Background. The cause of transient stress urinary incontinence during pregnancy remains uncertain. Anatomical change, such as a pressure effect of the enlarged uterus, changes in renal function, and alterations in bladder and urethral function have been proposed. There is little information about the role of reproductive hormones in stress urinary incontinence with onset during pregnancy. Methods. In a prospective, longitudinal, observational cohort study 200 consecutive women attending in early pregnancy were observed by repeated measurements of stress urinary incontinence, its possible determinants as well as serum concentrations of progesterone, estradiol and relaxin. Results. The prevalence rate of stress urinary incontinence increased to a stable level of about 25% from mid-pregnancy and increased with parity. A higher serum relaxin value early in pregnancy was correlated to a lower prevalence rate of stress urinary incontinence with onset during pregnancy, also when the influence of potentially important factors was taken into account in a multivariate analysis. No significant difference was shown regarding serum concentrations of estrogen or progesterone, maternal age, weight gain, time since last delivery or smoking, although this can be due to a small sample size. Conclusion. The reproductive hormone relaxin might have a role in maintaining urinary continence during pregnancy. A mechanism is uncertain.