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Placental progesterone, prostaglandins and mechanisms leading to initiation of parturition in the human.

Present knowledge allows the identification of some features of the initiation of human parturition. Progesterone reduces myometrial sensitivity to labour-inducing agents. It suppresses gap junction formation and facilitates beta-adrenergic receptor expression by the myometrium which, in turn, exerts a positive feedback by enhancing beta-adrenergic-induced increases in placental progesterone production. Inhibition of gestagen action does not result in immediate initiation of labor but sensitises myometrial cells to contraction-inducing agents. Estrogens, in contrast, enable the myometrium to prepare for parturition by inducing oxytocin receptors and this seems to be the first step towards parturition. Coordinated myometrial contractions are facilitated by the increased gap junctions due to the estrogen drive. Absence of estrogen will result in failed parturition. The myometrium seems to be sensitised to oxytocin by placental CRF. Myometrial CRF receptors increase their avidity for CRF with ongoing pregnancy. Oxytocin evokes a variety of auto- and paracrine events which culminate in increased free intracellular calcium and the consequent contractions. In this cascade, prostaglandins can be identified as positive feedback agents, as they further enhance estrogen-induced expression of oxytocin receptors. Another second messenger of oxytocin action are the inositol phosphates which can further increase free intracellular calcium concentrations. Finally, endothelin-1, derived from endometrium and decidua, under oxytocin control, may serve as a myometrial contractor following delivery when oxytocin concentrations decline but when a strong myometrial contraction is needed to prevent large blood loss during and after placenta expulsion.

Female↗

Relationships between changes in plasma concentrations of leptin before and after parturition and the timing of first post-partum ovulation in high-producing Holstein dairy cows.

During early lactation, dairy cattle are in negative energy balance and the delay to first post-partum ovulation depends on the time taken to recover from this situation. Lactating cows rely heavily on body fat to meet their requirements, leading to the suggestion that leptin, a hormone secreted mainly by adipocytes, is acting as a metabolic signal to sites that control the reproductive axis. The relationship between plasma leptin concentrations and the timing of the first ovulation post partum in 20 high-producing Holstein dairy cows, using a radioimmunoassay based on recombinant bovine leptin was studied. Plasma leptin concentrations declined after parturition, reached a nadir of 0.74 +/- 0.17 ng mL(-1) on 10.1 +/- 2.2 days after parturition (all values are mean +/- SEM). They then increased and became stable near the time of ovulation. Leptin concentrations averaged 1.81 +/- 0.31 ng mL(-1) in the 14 days prepartum, 1.32 +/- 0.21 ng mL(-1) in the post-partum preovulatory period and 1.61 +/- 0.24 ng mL(-1) in the post-ovulatory period. The differences between periods were significant (P<0.01). The interval from parturition to first ovulation averaged 25.9 +/- 2.0 days and was not correlated with the prepartum, preovulatory or post-ovulatory leptin values. However, the interval to first ovulation correlated significantly (r = 0.83 P < 0.0001) with the interval from parturition to the leptin nadir. These results show that plasma concentrations of leptin decrease in dairy cows in the early post-partum period and suggest that a delay in the recovery of leptin secretion increases the delay to the first ovulation.

Adipose Tissue↗

Recovery of long-term maternal behavioral deficiencies of neonatally underfed rats by early sensory stimulation: effects of successive parturitions.

The study examines the effects of two paradigms of neonatal food deprivation (daily mother-litter separation, Experiment 1 or nipple-ligation of mothers, Experiment 2) associated or not to early sensory stimulation (daily handling or the exposure to an enriched sensory environment) during the pre-weaning period of Wistar strain female rats. The effects of experimental manipulations were evaluated by measuring the nest building, retrieving latencies and nursing time of adult dams along three successive parturitions. Undernourished dams of Experiment 1, showed significant alterations in maternal responsiveness in the first delivery, which were attenuated by the maternal experience of two additional parturitions. Moreover, maternal alterations were importantly compensated by the association to early sensory stimulation (except nest building). Underfed mothers of Experiment 2 exhibited less alterations of the maternal response during the first parturition, and these were ameliorated by the maternal experience of successive parturitions. Additionally, complete recovery of maternal responsiveness alterations was obtained when sensory stimulation was associated to the maternal experience. Data suggest differential vulnerability to neonatal food and sensory deprivation of the neural mechanisms underlying maternal performance.

Animals↗

Macrophage migration inhibitory factor in patients with preterm parturition and microbial invasion of the amniotic cavity.

OBJECTIVE: Macrophage migration inhibitory factor (MIF) has emerged as an important mediator of septic shock. The administration of MIF increases lethality during endotoxemia, whereas neutralization of this cytokine prevents endotoxic shock and death associated with bacterial infection. The objective of this study was to determine whether there is a change in the amniotic fluid concentration of MIF in intra-amniotic infection and human parturition. STUDY DESIGN: A cross-sectional study was conducted in women in the following categories: (1) mid-trimester (n = 84); (2) preterm labor and intact membranes who delivered at term (n = 33), who delivered preterm (n = 53) and preterm labor with intra-amniotic infection (n = 23); (3) preterm premature rupture of membranes (PROM) with (n = 25) and without intra-amniotic infection (n = 26); and (4) term with intact membranes, in labor (n = 52) and not in labor (n = 31). MIF concentrations in amniotic fluid were determined using a sensitive and specific immunoassay. MIF concentrations in maternal plasma were also determined in patients with preterm labor and intact membranes. Immunohistochemistry was conducted in chorioamniotic membranes obtained from a different set of patients presenting with preterm labor with (n = 18) and without (n = 20) histologic chorioamnionitis. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to measure MIF mRNA expression in chorioamniotic membranes of patients with preterm labor with (n = 13) and without (n = 13) histologic chorioamnionitis. Parametric and non-parametric, receiver-operating characteristic (ROC) curve, survival analysis, and Cox regression model were used for analysis. RESULTS: Immunoreactive MIF was detectable in 96% (313/327) of amniotic fluid samples. The concentration of amniotic fluid MIF at term was higher than that in the mid-trimester (p = 0.004). Intra-amniotic infection in women with preterm labor and preterm PROM was associated with a significant increase in median amniotic fluid MIF concentration (p < 0.001 and 0.004, respectively). Patients with preterm labor with sterile amniotic fluid who delivered preterm had a significantly higher median amniotic fluid MIF concentration than those who delivered at term (p = 0.007). Among patients with preterm labor with intact membranes, survival analysis indicated that the median amniocentesis-to-delivery interval was significantly shorter in patients whose amniotic fluid concentrations of MIF were above 302 ng/ml than those below this cutoff value (p < 0.001). Human parturition at term was not associated with changes in the amniotic fluid MIF concentrations (p > 0.05). There was no significant difference in median maternal plasma MIF concentrations among patients with preterm labor and intact membranes who delivered at term, those who delivered preterm, and those who had intra-amniotic infection (p > 0.05 for all comparisons). Immunohistochemistry demonstrated that MIF protein was present in amniotic epithelial cells, and the mean percentage of immunoreactive MIF-staining cells was higher in patients with histologic chorioamnionitis than in those without this lesion (p = 0.03). Similarly, the mean MIF mRNA expression was higher in chorioamniotic membranes obtained from patients with histologic chorioamnionitis than in those without this lesion (p = 0.03). CONCLUSIONS: Intra-amniotic infection and preterm parturition, but not term parturition, are associated with a significant increase in amniotic fluid MIF concentrations. Among patients with preterm labor with intact membranes, elevated amniotic fluid concentrations of MIF are associated with intra-amniotic inflammation, histologic chorioamnionitis, and shorter amniocentesis-to-delivery interval. These changes in amniotic fluid were not reflected in maternal plasma. An increased expression of MIF protein and mRNA in chorioamniotic membranes was observed in patients with histologic choricamnionitis.

Amniocentesis↗

Effect of porcine relaxin on cervical dilatation, pelvic area and parturition in beef heifers.

Purified porcine relaxin (3,000 U/mg) was administered either into the cervical os or by intra-muscular injection to crossbred beef heifers beginning 4 days before expected parturition, in an attempt to elucidate the physiological roles of relaxin in cervical dilatation, the pelvic area, and parturition. Relaxin (3,000 U in a gel vehicle), when administered into the cervical os during late pregnancy, induced significant dilatation of the cervix 8 and 16 h later, as compared to vehicle-treated controls. This induced cervical dilatation did not cause premature parturition in relaxin-treated heifers and was similar to controls. Exogenous relaxin during late gestation elicited an increased growth rate of the pelvic area, as determined by sequential measurements of height and width of the pelvic canal. These results indicate that, before parturition, pelvic width increased more rapidly than pelvic height and that exogenous relaxin elicited a greater response in both parameters. Highly significant nocturnal elevations in concentrations of progesterone in peripheral blood serum occurred in vehicle-treated control heifers during late pregnancy. These nocturnal elevations in serum levels of progesterone were significantly reduced after 8 and 16 h of relaxin treatment in experimental animals as compared to control heifers. The mechanisms by which porcine relaxin reduces ovarian progesterone secretion in beef heifers remain undefined.

Animals↗

Variation of cytoplasmic content of estrogen and progesterone receptors in the mammary gland and uterus of rats at time of parturition.

The cytoplasmic content of estrogen and progesterone receptors (ERc and PRc) was measured in the rat uterine and mammary tissues during the period from late pregnancy through lactation. Uterine ERc and PRc, which sedimented at the 8S and 4S regions, respectively, of a 5-20% sucrose gradient, showed similar rise and decline patterns before and after parturition. Following a decline from the 15th day (114 +/- 13.7 fmol/mg protein) to the 20th day of pregnancy (57.7 +/- 10.2 fmol/mg protein), ERc levels increased almost 2.5-fold at the time of parturition. A decrease to the predelivery level by 24 h post-delivery was followed by a steady increase to 270.6 +/- 46 fmol/mg protein by 15 days of lactation. Uterine PRc levels also showed a peak similar to that of ERc at the time of parturition (24.3 +/- 1.1 fmol/mg protein). The level of ERc in mammary gland 6 h postpartum was the lowest (1.5 +/- 0.3 fmol/mg protein) and during the first 10 days of lactation ERc levels were maintained at about 10 fmol per mg of cytosol protein. Results herein suggest that levels of these steroid receptors may be hormonally regulated and that the uterus and mammary gland may have a different sensitivity to these regulatory control mechanisms. The physiological significance in the variation of these receptors in conjunction with the onset of parturition is discussed.

Animals↗

Prolongation of parturition in the pregnant rat following treatment with a platelet activating factor receptor antagonist.

The presence of platelet activating factor (PAF) in amniotic fluid of women only in labor is indicative of a role for PAF in parturition. In addition, stimulated amnion membrane produces both PAF and prostaglandin E2, each of which is capable of inducing myometrial contraction. To evaluate the involvement of PAF in the process of parturition, we administered the PAF receptor antagonist, L-659,989, to 17-day timed pregnant rats and followed the events of labor and delivery. Administration by mouth with L-659,989 of three concentrations (1.6, 16, and 48 mg/kg/day) did not alter the gestational period; however, the duration of parturition was increased from 2-fold to 5-fold by such treatment. No toxicity of the analog was apparent; treated dams showed no signs of morbidity, and fetal mortality was not significantly altered by treatment with the antagonist. Based on these experiments, it is suggested that the PAF receptor antagonist interferes with the normal progression of events of parturition and that PAF is an integral mediator in initiating the myometrial contraction necessary for expulsion of the fetus.

Animals↗

Changes in the expression of the L-type voltage-dependent calcium channel during pregnancy and parturition in the rat.

The L-type voltage-dependent calcium channel (L-VDCC) is assumed to be a critical component of excitation-contraction coupling in smooth muscle. Using pregnant rat myometrium, we examined the hypothesis that parturition is associated with significant changes in the expression of the alpha 1 subunit of the L-VDCC at the mRNA or protein level. The binding of radiolabeled dihydropyridine, which correlates with the total number of calcium channels in the membrane, was increased by 14 days' gestation, in comparison to that in nonpregnant controls. The elevation in binding capacity persisted through labor and fell postpartum. Northern and RNA dot-blot analysis demonstrated the highest level of expression on Days 20 and 21, with a 3- to 10-fold decrease during parturition. We believe these studies are most consistent with a one-day lag time between mRNA and protein expression, and generally support a modest increase in L-VDCC expression in pregnancy and labor. Reverse transcriptase polymerase chain reaction was used to examine changes in isoform expression in Motif IV, a region of the alpha 1 subunit known to be alternatively spliced. These studies revealed the presence of multiple isoforms in rat myometrium, with a predominance of IVS3B. Interestingly, a marked increase in the ratio of S3B:S3A was noted at parturition. In summary, these data demonstrate that the number of L-type calcium channels, although increased in pregnancy, do not change prior to, or with the onset of, myometrial contraction. Intriguingly, mRNA expression was markedly decreased at parturition. The change in isoform expression during labor is of unknown, but potential, physiologic significance.

Animals↗

Nitric oxide prolongs parturition and inhibits maternal behavior in rats.

We examined the effect of nitric oxide (NO) on the process of parturition in rats. Subcutaneous injection of the NO donor sodium nitroprusside (SNP) in late pregnancy prolonged the total parturition time. The effect of N omega-nitro-L-arginine was not significantly different from that of saline. Intracerebroventricular injection of SNP in parturient rats delayed the progress of parturition. Both modes of SNP treatment also inhibited expression of maternal behavior. Central injection of oxytocin (OXT) with SNP failed to reduce parturition time significantly, but intrapartum, not postpartum, maternal behaviour was restored. These observations suggest that NO interferes with the release of OXT within the brain, hence affecting the initiation of maternal behaviour, and may also impair oxytocin secretion from the neurohypophysis.

Animals↗

Parturition upregulates nitric oxide synthase activity in the rat anterior pituitary gland.

Recent evidence suggests that endogenous nitric oxide (NO) contributes to the modulation of hormonal secretion from the anterior pituitary gland according to the physiological state of the animal. In this study, nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry and specific neurochemical assay were used to asses possible changes of NO synthase (NOS) activity in the anterior pituitary during pregnancy and parturition in rats. The anterior pituitary showed (weak) NADPH-d activity throughout pregnancy. Parturition increased the number and intensity of NADPH-d-positive cells. The NADPH-d-positive cells co-localized with immunofluorescent LH-positive cells. No variation in NADPH-d activity was apparent during the various stages of the oestrous cycle. Furthermore, NOS activity during parturition increased significantly when compared with non-pregnant and pregnant rats. Increases in both specific activity and NADPH-d activity gradually decreased within 24 h post-partum, suggesting that NO may modulate anterior pituitary function during parturition.

Animals↗

Changes in oxytocin immunoreactivity and mRNA expression in the sheep brain during pregnancy, parturition and lactation and in response to oestrogen and progesterone.

The effects of pregnancy, parturition and lactation and exogenous treatments with oestradiol and progesterone on oxytocin (OXY) immunoreactivity and gene expression in the sheep brain were investigated. Immunocytochemistry was used to demonstrate that increased OXY-immunoreactivity occurred in cells of the paraventricular (PVN) and supraoptic nuclei (SON), the bed nucleus of the stria terminalis (BNST), the anterior commissural nuclei (ACN) and the periventricular part of the medial preoptic area (PvMP). Oxytocin immunoreactive terminals were also seen in the accessory olfactory nucleus, the glomerular and peri-glomerular layers of the olfactory bulb, the lateral septum, the zona incerta and the pars compacta of the substantia nigra. Compared to ovariectomized and late pregnant animals, the intensity of immunoreactivity was increased in all of these oxytocinergic elements at parturition, during lactation and following exogenous treatment with oestradiol. The OXY-immunoreactivity was also more intense in late pregnant animals compared to ovariectomized ones. Quantitative in situ hybridization histochemistry showed that cells in the PVN, SON, BNST and PvMP all showed significantly increased expression of OXY mRNA in animals at parturition and during lactation compared to late pregnant or ovariectomized animals. Expression levels in late pregnant animals were also significantly higher than in ovariectomized ones. Progesterone treatment significantly increased OXY mRNA in the PVN, SON, BNST and PvMP whereas oestradiol treatment was only effective in the PVN, BNST and PvMP. Combined treatment with these steroids did not significantly increase OXY mRNA levels in comparison with their administration alone. These results show that OXY-immunoreactivity and mRNA expression are at their highest in the sheep brain when maternal behaviour is induced. The increased synthesis/storage of the peptide at parturition may be due to changes in circulating concentrations of both progesterone and oestradiol during late pregnancy.

Animals↗

Blood levels of prostaglandin metabolites (PGFM, PGEM) after parturition in cows with and without retained placenta considering spontaneous calving and dystocia.

Blood samples were taken from 71 Holstein Friesian cows at 0, 3, 24 and 48 hours after parturition. Peripheral plasma concentrations of prostaglandin F2 alpha and E2 metabolites (PGFM, PGEM) were determined by radioimmunoassay. The cows were divided into 4 groups, according to type of calving (spontaneous, dystocia) and discharge of placenta. Group 1: spontaneous calving, shedding of placenta within 12 hours (SC, NRP, n = 19); group 2: spontaneous calving, retained placenta (SC, RP, n = 7); group 3: Dystocia, shedding of placenta within 12 hours (Dys, NRP, n = 32); group 4: Dystocia, retained placenta (Dys, RP, n = 13). The PGFM concentrations decreased within 3 hours after parturition only in NRP cows (groups 1 and 3, p < 0.05). Three hours after calving the animals of group 3 had considerably higher PGFM levels than those in group 4 (0.46 +/- 0.26 vs 0.26 +/- 0.11 ng/ml). Significant decreases (p < 0.05) in PGEM concentrations occurred in cows that shed the placenta within 24 hours after parturition. Cows that retained the placenta showed a significant slower decrease of the PGEM levels. It is concluded that postpartum prostaglandin levels are influenced by stress during parturition (dystocia, transportation) as well as by retained placenta.

Animals↗

Comparative hemostatic protein alterations accompanying pregnancy and parturition.

Pregnancy and parturition represent adaptive, physiological stress situations that elicit both blood coagulation protein changes and endocrine alterations. This paper briefly reviews the interrelationships of these responses by comparing the available data in several mammalian species including man, dog, cow, and pig. Hemostasis is an enzymatically controlled cascade process involving platelets and specific coagulation proteins that results in the formation of insoluble strands of fibrin. Although qualitatively similar in most mammals, quantitative differences exist in the circulating levels of individual coagulation proteins which may contribute towards the different rates of clot formation. In the late gestation stage of human pregnancy, significant increases are observed in the circulating biological activities of the coagulation factors VII, VIII:C, IX, and X. In the dog, the activities of factors VII and IX reach peak values in midpregnancy, while in the cow little or no changes are observed except for factor VII values which show a significant increase only around the time of parturition. These coagulation changes appear to be associated with fluctuations in circulating hormone values, particularly plasma estrogen. In human pregnancy, the circulating levels of fibrinogen, the precursor of fibrin, increase during the gestation period reaching maximum values during and immediately following parturition. In the dog and the cow two distinct increases in fibrinogen values are observed, the first in the midgestation period and the second in the immediate postparturition period. In the pig, fibrinogen values also rise significantly at parturition. Oral contraceptive studies in the human female have indicated that changes in circulating activities of coagulation proteins are hormonally influenced.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Regression of the corpus luteum of pregnancy following parturition in the ewe.

Corpora lutea (CL) of pregnancy from single-lambing ewes were examined by light and electron microscopy within 24 h and at 8, 15, 23, 31 and 41 days after parturition (2 ewes per stage). Within 24 h of parturition the structure of the CL was well preserved and both large and small luteal cells, characteristic of this species, were present in substantial numbers. However, both types of luteal cell contained numerous cytoplasmic lipid droplets, and smooth endoplasmic reticulum and secretory granules in large luteal cells were less prominent than in normal functional CL of cyclic ewes. Leucocytic infiltration, and death of some luteal and endothelial cells, were also observed at this stage. Further regression of the CL progressed slowly, and lipid-rich large luteal cells were still readily recognisable 15 days after parturition. The size of the CL declined progressively, and the proportion of tissue occupied by intercellular substances increased. Corpora albicantia approximately equal to 3-4 mm in diameter were still recognisable 41 days after parturition. It was concluded that luteal regression post partum progresses much less rapidly than at the end of the oestrous cycle.

Animals↗

Fate of vasoactive biogenic amines and activity of enzyme phenylethanolamine-N-methyltransferase in rat adrenal gland during the course of pregnancy, parturition and postpartum.

Influence of pregnancy, parturition and postparturition upon natural evolution of adrenaline, dopamine and enzyme of adrenaline synthesis, phenylethanolamine-N-methyltransferase in the adrenal gland was studied. Adrenaline content of the adrenal gland showed a progressive decrease from the 14th to the 18th day postcoitum. The mean values for adrenaline remained lower than the value of day 14 throughout the course of pregnancy up to day 21 postcoitum. At parturition (0 to 4 h) adrenaline declined again to its minimum value but was accompanied by an increase in the adrenal adrenaline level 24 h postpartum. The activity of enzyme phenylethanolamine-N-methyltransferase followed a similar pattern of evolution as that of adrenaline during pregnancy and postpartum. Dopamine concentration of the adrenal gland showed nonsignificant increases during days 14--18 postcoitum. At day 20 postcoitum adrenal dopamine was decreased to its minimum value and this decrease persisted up to day 21 postcoitum. At day 22 postcoitum, adrenal dopamine increased sharply to its maximum value but was again back to the level of day 21 at 0 h parturition. At 24 h postpartum, dopamine content decreased maximally again. The results presented here suggest that the content of vasoactive biogenic amines and the enzyme of adrenaline synthesis go through important natural variations during pregnancy, parturition and postpartum from day 14 postcoitum to 24 h postpartum. This phenomenon does not seem to be merely a cyclic effect. All these variations can be attributed to modified endocrine activity of the pregnant animals by correlating natural variations in steroid hormone levels with the observed changes in biogenic amines, since it is well established that most of the hormonal and nonhormonal steroids affect catecholamine regulation. The observed changes in amine levels could have important influence for the termination of pregnancy.

Adrenal Glands↗

Genetic analysis of fetal development and parturition control in the mouse.

The application of targeted gene inactivation methodologies to the study of late fetal development and control of the timing for parturition in mice has yielded insight into the mechanisms that enhance fetal survival. An essential role for glucocorticoids in promoting lung maturation sufficient for viability ex utero before the onset of normal parturition has been demonstrated in corticotropin-releasing hormone-deficient mice. In contrast, maternal deficiency in the prostaglandin synthetic enzyme cyclooxygenase-1 results in the markedly delayed onset of labor and fetal demise because of postdates gestation. The complex interplay of factors that govern the onset of labor is highlighted by mice deficient in both cyclooxygenase-1 and oxytocin. Whereas mice deficient in oxytocin demonstrate normal parturition, simultaneous cyclooxygenase-1 and oxytocin deficiency rescues the delayed onset of labor found in cyclooxygenase-1 knockout mice but results in the prolonged duration of labor. The consequences of complete deficiency of molecules involved in parturition in mice suggest novel interventions for human preterm labor.

Animals↗

Oxytocin receptors and parturition. II. Concentrations of receptors for oxytocin and estrogen in the gravid and nongravid uterus at term.

It has been postulated that intrauterine volume plays a role in the timing of parturition. In previous studies we found that the onset of parturition in the rat was associated with marked increases in the concentrations of receptors for estrogen and oxytocin in the myometrium. To determine the effects of intrauterine volume on the concentrations of these myometrial receptors, we compared receptor levels in gravid and nongravid uterine horns from unilaterally pregnant rats at or near the time of parturition. Myometria from gravid horns contained substantially greater concentrations of DNA and protein per horn than did myometria from the contralateral nongravid horns. The amounts of receptors per horn for estrogen in the nuclear and cytosol fractions and for oxytocin were 7.5, 5.2, and 4.5 times greater, respectively, in myometria from gravid horns. However, the concentration of receptors per cell was the same in gravid and nongravid horns at or near parturition. These results suggest that uterine stretch causes hyperplasia and hypertrophy of the myometrium, indicative of more DNA and protein per gravid horn than nongravid horn. The sharp rise in concentration per cell of receptors for estrogen and oxytocin occurring about the time of labor, however, appears to be induced by hormonal and not physical factors.

Animals↗

Radioimmunoassay of relaxin throughout pregnancy and during parturition in the rat.

Relaxin immunoactivaity concentrations in the peripheral sera been measured during pregnancy and parturition in rats with a homologous rat relaxin RIA. Relaxin was not detected until day 10 of pregnancy (day 10). Relaxin levels increased markedly over the next 4 days and generally ranged between 50-100 ng/ml from days 14-20. A prepartum surge in relaxin levels, which appeared to be associated with the photoperiod, occurred on day 21 in unanesthetized rats bled via indwelling jugular cannulas. Mean relaxin levels in these animals increased sharply from less than 80 ng/ml on day 20 to approximately 140 ng/ml at 1400 h on day 21 and declined to less than 60 ng/ml during the 12-24 h preceding parturition. The prepartum surge in relaxin immunoactivity may be associated with luteolysis, since there was an accelerated decline in progesterone concentrations concurrent with the prepartum relaxin surg. Rats also experienced a surge in relaxin concentrations during parturition. The mean maximal level of relaxin during parturition was approximately 180 ng/ml. The rate of decline of rat relaxin immunoactivity levels after bilateral ovariectomy on day 21 demonstrated characteristics of a multiexponential curve. The mean clearance t 1/2 from 0-30 min was 22 +/- 3 min (+/- SEM), and the mean t 1/2 from 30-180 min was 56 +/- 7 min (+/0 SEM).

Animals↗