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Query: UNIPROT:P30536 (PBS)
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This study examined the influence of ovarian steroids on the uterotropic actions of relaxin (RLX) in ovariectomized prepubertal gilts. Ovariectomized gilts received (im) corn oil (CO), estradiol benzoate (EB), or EB and progesterone (P) for 0-16 days. Steroid administration was patterned to approximate the plasma concentrations of endogenous ovarian steroids observed during 1) the follicular phase (EB), 2) luteal phase (EB+P), and 3) early pregnancy (EB+P+EB). Half of each group also received PBS or 0.5 mg RLX every 6 h for 54 h, coinciding with the final 2 days of the experimental period. After hysterectomy, uterine tissues were analyzed for water, dry matter, protein, DNA, glycosaminoglycans (GAGs), and collagen contents. Administration of EB or P increased uterine weight 5- to 6-fold, but no differences were observed between EB+P- and EB+P+EB-treated gilts. Cotreatment with RLX enhanced steroid-induced uterine growth 40-70%, and RLX stimulated growth in CO- and EB+CO control gilts 2- to 3-fold. The water content of uterine tissues was greater in EB-, EB+P-, and EB+P+EB-treated gilts than in their respective controls, and this response was augmented by RLX in all treatment groups. Administration of steroids stimulated a 4- to 5-fold increase in uterine dry weight compared to that in controls, with responses not differing between EB+P- and EB+P+EB-treated gilts. In all groups, RLX increased uterine dry weight. Protein and DNA contents of uterine tissue increased with steroid treatment, but neither variable differed between EB+P- and EB+P+EB-treated gilts. Administration of RLX, alone or in combination with steroids, increased protein and DNA contents of uterine tissues. The tissue content of GAGs increased in response to steroids, and coadministration of RLX did not alter this response. Although the uterine tissue concentration of collagen was reduced in steroid- and RLX-treated gilts, the collagen content of the uterus was not affected by the various treatments. The results of this study indicate that RLX is a potent stimulator of uterine growth under a variety of steroidal environments. RLX- or steroid-induced uterine growth was manifest by increased water, dry matter, protein, and DNA and GAG contents, but the uterine content of collagen was not affected. The overall growth-promoting effects of EB and the stimulation of DNA accretion by RLX were not observed when gilts were cotreated with P.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Influence of ovarian steroids on relaxin-induced uterine growth in ovariectomized gilts. 159 36

Purified pig relaxin (3000 U/mg) was injected i.m. into pregnant Holstein dairy heifers on Day 276 or 277 to determine its effect on parturition and sequential measurements of the pelvic area, cervical dilatation, and peripheral blood-plasma concentrations of progesterone and relaxin. Treatments included phosphate-buffer saline (2 ml, Group C, N = 7), relaxin once (1 mg, Group 1R, N = 7), and twice (2 mg, 12 h apart; Group 2R, N = 7). Intervals (mean +/- s.e.) between the first injection of relaxin or PBS and calving were 64 +/- 17, 80 +/- 19 and 125 +/- 34 h for Groups 2R, 1R and C, respectively. The calving intervals were reduced in Groups 2R (P less than 0.01) and 1R (P less than 0.05) compared with Group C. The incidence of dystocia was 29% (2 of 7) in Group 2R and 43% (3 of 7) in Group 1R compared with 57% (4 of 7) in Group C (P less than 0.01). Body weights and ratios of males to females of the calves were similar (P greater than 0.05) between groups. Progesterone plasma concentrations decreased (P less than 0.01) earlier in Groups 1R and 2R compared with Group C, and this acute decrease began within 6 h of treatment. At 24 h after relaxin or PBS injection, progesterone concentrations were 2.7 +/- 1.1 ng/ml for Group 2R, 3.5 +/- 0.9 ng/ml for Group 1R, and 6.0 +/- 0.1 ng/ml for Group C. Relaxin reached peak blood-plasma levels of 19 +/- 2.2 ng/ml 1 h after injection of relaxin, but remained unchanged, 0.3 +/- 0.01 ng/ml, in Group C. Pelvic area was increased 26%, 22% and 14% and cervical dilatation was increased 109%, 76% and 53% 48 h after injection in Groups 2R, 1R and C, respectively, but these responses were similar among groups at the time of parturition. We conclude that two i.m. injections of relaxin facilitated earlier calving, acutely decreased progesterone secretion, increased cervical dilatation and pelvic area expansion, and decreased the incidence of dystocia in dairy heifers.
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PMID:Effect of relaxin on facilitation of parturition in dairy heifers. 201 82

The purpose of this investigation was to use an approach targeted specifically on endogenous relaxin to determine the influence of antepartum (days 20-22) relaxin on cervical modifications and birth in the rat. To that end, a monoclonal antibody specific for rat relaxin, designated MCA1, was used to neutralize endogenous relaxin in intact pregnant rats. MCA1 or PBS vehicle was administered iv to intact rats daily from days 20-22 of pregnancy. Cervices were removed at 1200 h on day 22. Cervices obtained from MCA1-treated rats were less extensible than cervices obtained from PBS-treated control rats. Furthermore, wet weight, dry weight, water content, and uronate content were lower in cervices obtained from MCA1-treated rats than in cervices from PBS-treated controls. Birth and maternal behavior of MCA1-treated and PBS-treated control rats were observed continuously from 2100 h on day 22 until day 2 postpartum (d2PP). MCA1-treated rats exhibited significantly prolonged durations of litter delivery as well as reduced incidences of live pups on d2PP compared with controls. There were lower incidences of normal maternal behavior observed at birth and on d1PP with MCA1-treated rats than with control rats. In addition, little or no milk was observed in the abdomen of most live pups of MCA1-treated rats on d2PP, whereas abundant milk was observed in the abdomen of all live pups of control rats. The mean live pup weight on d2PP was lower in the litters of MCA1-treated rats than in control litters. The present study indicates that in the rat endogenous relaxin is needed during the antepartum period for normal cervical growth and extensibility, normal litter delivery, and high postpartum pup survival. This work supports the hypothesis that the influence of endogenous relaxin on birth is attributable, at least in part, to its effects on the cervix.
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PMID:Monoclonal antibodies specific for rat relaxin. IV. Passive immunization with monoclonal antibodies during the antepartum period reduces cervical growth and extensibility, disrupts birth, and reduces pup survival in intact rats. 273 47

Porcine corpora lutea persist beyond 150 days in hysterectomized animals compared with about 114 days during normal pregnancy. To explore the mechanism(s) regulating the peak release of relaxin and secretion of progesterone by aging corpora lutea and to examine the direct effect of purified porcine (p) PRL on such corpora lutea, hypophysial stalk transection (HST), hypophysectomy (HYPOX) with or without PRL replacement, and sham operation control (SOC) were conducted on day 110 (estrus = day 0) on purebred Yorkshire gilts that were hysterectomized on days 6-8. The pPRL (0.5 mg every 6 h daily) or PBS (0.5 ml every 6 h daily) was given iv from days 110-120. HYPOX + pPRL, HYPOX + PBS, HST + PBS, and SOC + PBS formed four experimental groups. Peak relaxin concentrations in peripheral plasma (mean values ranged from 22-24 ng/ml) occurred on about day 113 for all groups [113.4 +/- 0.3 days (+/- SE)] regardless of the different surgical interventions. After peak release, relaxin decreased steadily in the HYPOX + PBS group, falling to less than 1.0 ng/ml by 6 days later, whereas relaxin in other groups remained elevated (approximately 7 ng/ml). In the HYPOX plus PBS group, progesterone decreased abruptly, remaining below 1 ng/ml from 1 week onward, lower (P less than 0.01) than that in controls (approximately 19 ng/ml); in the HYPOX + pPRL group, progesterone levels (approximately 17 ng/ml) remained similar (P greater than 0.05) to those in controls (approximately 19 ng/ml) and the HST + PBS group (approximately 15 ng/ml). These results clearly reveal that the pituitary gland plays no direct role in regulating the timed peak release of relaxin from aging corpora lutea in hysterectomized gilts and that the peak release of relaxin on about day 113 is preprogrammed and inherent within such aging luteal cells. This study provides strong evidence that purified pPRL maintains both relaxin and progesterone secretion as well as the morphology of aging corpora lutea for at least 10 days after hypophysectomy in hysterectomized gilts.
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PMID:Prolactin maintains relaxin and progesterone secretion by aging corpora lutea after hypophysial stalk transection or hypophysectomy in the pig. 291 12

Relaxin is required for normal delivery in the rat. The mechanism(s) whereby relaxin contributes to rapid and safe delivery of the fetuses, however, has not been established. The purpose of this investigation was to determine if relaxin enables normal delivery by promoting the growth and modifying the tensile properties of the uterine cervix. To that end, a monoclonal antibody specific for rat relaxin, designated MCA1, was used to passively neutralize endogenous relaxin in intact pregnant rats. MCA1 or PBS vehicle was administered iv to rats daily from days 12-22 of pregnancy. Cervices were removed at 1200 h on day 22. Cervices obtained from MCA1-treated rats were much smaller and far less extensible than cervices obtained from control rats. Moreover, cervices from MCA1-treated rats were less able to accommodate stress created by extension than cervices from control rats. Passive neutralization of relaxin had no influence on 1) the weights of other reproductive tissues (uterus, placenta, and ovary), 2) the number of fetuses, and 3) the viability of fetuses. The present study indicates that in the rat endogenous relaxin is required for promoting cervical growth and softening during the second half of pregnancy. This work supports the hypothesis that the influence of endogenous relaxin on birth is attributable, at least in part, to its effects on the cervix.
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PMID:Monoclonal antibodies specific for rat relaxin. III. Passive immunization with monoclonal antibodies throughout the second half of pregnancy reduces cervical growth and extensibility in intact rats. 316 31

Purified porcine relaxin (3000 U/mg) was administered into the cervical os of primiparous beef heifers on day 278 of gestation (approximately 5 days before parturition normally occurs) to determine its effects on the induction of parturition, changes in progesterone, estrone (E1), 17 beta-estradiol (17 beta-E2), cervical dilation, and pelvic relaxation. Heifers were assigned randomly to 1 of 3 treatments: relaxin-double (two infusions of 3000 U, 12 h apart; n = 17), relaxin-single (3000 U; n = 14), and PBS-gel vehicle (n = 16). Relaxin induced marked earlier calving (P less than 0.002) than PBS-gel vehicle. The intervals between the administration of relaxin or the PBS-gel vehicle and calving were 2.0, 2.5, and 5.3 days for heifers given relaxin-double, relaxin-single, and PBS-gel vehicle, respectively. The duration of gestation was significantly reduced (P less than 0.002) in relaxin-treated heifers compared with that in control heifers. A precipitous decrease in progesterone (7.1 ng/ml) occurred in peripheral blood plasma within 24 h after relaxin treatment. Coincident with a decline in levels of progesterone, E1 and 17 beta-E2 increased by 1700 and 400 pg/ml, respectively, an increase of 35% compared with the 12% increase in these steroids in control heifers. Mean deviations of cervical dilation increased 643%, 526%, and 11% in heifers given relaxin-double, relaxin-single, and PBS-gel vehicle, respectively. Relaxin induced maximum pelvic opening between 12-36 h after treatment. Although relaxin induced significantly earlier calving, there was no incidence (0 of 31 heifers) of retained placenta. We conclude from this study that purified relaxin administered intracervically to primiparous beef heifers during late pregnancy induced premature parturition. Marked shifts of progesterone, E1, 17 beta-E2, pelvic canal expansion, and cervical relaxation reflect the premature parturition induced by relaxin.
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PMID:Relaxin on induction of parturition in beef heifers. 375 33

Purified porcine relaxin (3000 U/mg) was administered im (RLX-IM; 1 mg; n = 2) and in the cervical os (RLX-OS; 1 mg; n = 2) on day 273 (approximately 10 days before parturition normally occurs) of gestation to determine the profiles of immunoreactive relaxin and its effects on progesterone, estrone (E1), and 17 beta-estradiol (17 beta-E2) secretion in peripheral blood plasma of beef heifers. Controls received either 0.01 M PBS (1 ml, im; n = 2) or 0.01 M gel-PBS (gel; 1 ml, os; n = 2) in cervical os. One relaxin-treated (im) heifer calved at 4 h and 36 min after treatment; thus, data from this heifer were not included in subsequent analysis. Relaxin-treated heifers showed an acute elevation in relaxin, a precipitous decrease in progesterone, and a significant (P less than 0.05) elevation of E1 and 17 beta-E2. Plasma relaxin levels were 4.95, 1.5, and 0.24 ng/ml at 0.5 h in RLX-IM, RLX-OS, and control animals, respectively. Peripheral plasma relaxin peaked between 23-31 ng/ml 1-2.5 h before returning to less than 0.5 ng/ml 5-12 h after treatment. Relaxin administration accounted for 70%, 73%, and 58% of the progesterone, E1, and 17 beta-E2 variability between treatments, respectively. An abrupt decrease (P less than 0.01) in progesterone preceded the rises (P less than 0.05) in E1 and 17 beta-E2 at 1.5, 2-2.5, and 2-3.5 h, respectively. Maximum progesterone deviations from the pretreatment mean concentration were -5.43, -3.05, and -0.92 ng/ml for RLX-IM, RLX-OS, and controls. Progesterone rebounded from 36% to 61% and 62% to 79% of respective pretreatment means for RLX-IM and RLX-OS. Peak elevation of E1 was 407.3, 306.5, and 71.5 pg/ml and that of 17 beta-E2 was 82.2, 35.8, and 7.8 ng/ml for RLX-IM, RLX-OS, and controls, respectively. These results provide strong evidence that a pharmacological dosage of relaxin induces an acute depression of progesterone secretion beginning within 90 min in beef heifers during late pregnancy. We suggest that these early and marked luteolytic effects of relaxin on progesterone secretion in cattle could be by direct or indirect actions via mechanisms that are yet unknown.
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PMID:Acute decrease in progesterone and increase in estrogen secretion caused by relaxin during late pregnancy in beef heifers. 378 May 65

Recent studies demonstrated that exogenous relaxin promoted drinking in nonpregnant rats. The purpose of this investigation was to determine the influence of endogenous relaxin on water consumption in pregnant rats. To that end, a monoclonal antibody specific for rat relaxin, designated MCA1, was used to passively neutralize endogenous relaxin throughout the second half of pregnancy in intact rats. Five milligrams of highly purified MCA1 were administrated iv to rats daily from days 12-22 of pregnancy. Controls received either a monoclonal antibody for fluorescein (monoclonal antibody control) or PBS (vehicle control). The amount of water consumed and both the total duration of water consumption and the total number of episodes when water was consumed were determined daily during both dark and light periods for all treatment groups. From days 13-22 of pregnancy, all three of these parameters of water consumption increased during the 10-h dark period (P < 0.01), but not during the 14-h light period. The mean daily water consumption in MCA1-treated rats was significantly less than that in controls (P < 0.05). Relaxin's effects on water consumption were limited to the 14-h light period (P < 0.01). No difference was found in daily water consumption between the MCA1-treated and control groups during the 10-h dark period. There was a tendency during the light period for both the total duration of water consumption (P = 0.06) and the total number of episodes when water was consumed (P = 0.13) to be less in MCA1-treated rats than in controls. Food consumption and body weight increased as pregnancy progressed, but no differences were found among the three treatment groups. We conclude that endogenous relaxin has effects on water consumption. It promotes water consumption during the daily light period in the second half of pregnancy in rats. Thus, relaxin may be a dipsogenic agent.
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PMID:Monoclonal antibodies specific for rat relaxin. VIII. Passive immunization with monoclonal antibodies throughout the second half of pregnancy reduces water consumption in rats. 772 Jun 35

A study was conducted to examine the influence of ovarian steroids on relaxin-induced changes in distensibility and composition of the uterine cervix in gilts. Ovariectomized, prepubertal gilts received (i.m.) either 1) 0.5 ml corn oil (CO) for 16 days; 2) 0.5 ml CO for 16 days and estradiol benzoate (EB; 200 micrograms) twice daily on Days 13-14; 3) EB on Days 0-1 followed by CO on Days 3-16 (EB + CO); 4) EB on Days 0-1 followed by CO on Day 2 and twice daily injections of 100 mg progesterone (P) on Days 3-16 (EB + P); or 5) EB on Days 0-1 followed by CO on Day 2 and P on Days 3-16 with additional EB treatment on Days 13-14 (EB + P + EB). One half of each group also received (i.m.) 0.5 ml 0.1 M PBS or 0.5 mg relaxin (RLX) every 6 h for 54 h coinciding with the final 2 days of the experimental period. Administration of RLX increased (p < 0.05) cervical distensibility compared to PBS treatment, with the response being greater (p < 0.05) in EB-, EB + CO-, and EB + P + EB-treated gilts compared to CO- or EB + P-treated gilts. Water content of cervical tissue was greater (p < 0.05) in EB-, EB+P- and EB + P + EB-treated gilts compared to CO- or EB + CO-treated gilt: and in all treatments, RLX enhanced (p < 0.05) imbibition of water by cervical tissues compared to that in PBS-treated gilts.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Influence of ovarian steroids on relaxin-induced distensibility and compositional changes in the porcine cervix. 831 89

It is established that endogenous relaxin promotes the growth and development of the cervix, mammary glands, and nipples in pregnant rats. Additionally, the observation that porcine relaxin promotes growth of the vagina in both nonpregnant and pregnant rats provides indirect evidence that endogenous relaxin may effect growth of the vagina during rat pregnancy. The purpose of this study was to determine whether endogenous relaxin promotes growth of the vagina in pregnant rats. To that end, a monoclonal antibody, specific for rat relaxin, designated MCA1, was used to passively neutralize endogenous relaxin throughout the second half of pregnancy in intact rats. Five milligrams of highly purified MCA1 were injected iv to rats daily from days 12-22 of pregnancy. Controls received either a monoclonal antibody for fluorescein or PBS. The vaginal wet weight, dry weight, length, diameter, inner surface area, DNA content, and percent water content were determined. No differences were found between monoclonal antibody for fluorescein and PBS controls for any of the measured vaginal parameters. In contrast, values for all physical parameters, except percent water content, were significantly lower in MCA1-treated rats than in controls. Vaginal DNA content was also lower in MCA1-treated rats than in controls; and this observation supports the view that relaxin induces vaginal growth at least in part by promoting cell proliferation. To examine the mechanism of relaxin's apparent action on the vagina, specific relaxin-binding sites were localized immunohistochemically. Relaxin-binding sites were found in epithelial and smooth muscle cells, and the binding was specific for relaxin. We conclude that endogenous relaxin promotes growth of the vagina in pregnant rats.
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PMID:Monoclonal antibodies specific for rat relaxin. IX. Evidence that endogenous relaxin promotes growth of the vagina during the second half of pregnancy in rats. 859 85


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