All of these properties could make it a potential therapeutic target for the treatment of certain diseases. The control of relaxin release in humans is not fully understood. It remains unclear whether relaxin can feed back to the pituitary or the fetus to affect luteinising hormone or human chorionic gonadotrophin levels and so control its own release.
Relaxin carries out its actions on the reproductive system and other organs by activating specific receptors on these tissues. Disorders of relaxin secretion have not been described in detail. Studies have suggested that high levels of circulating relaxin in the mother are associated with premature birth, presumably via its effects on the rupture of the fetal membranes and the opening of the cervix.
However, further research is needed to confirm these findings. There is some evidence that low levels of relaxin may contribute to a condition known as scleroderma, where the skin thickens and hardens. This is caused by the development of fibrosis and scarring on the skin, which also occurs in the lung, stomach and blood vessels. About Contact Events News.
Search Search. Relaxin can also play a role in round ligament pain symptoms. The round ligaments are a pair of cordlike structures in the pelvis that help support the uterus by connecting the front of the uterus to the groin.
Like your other ligaments, the round ligaments become softer and stretch during pregnancy, which can be rather painful, especially during rapid, repetitive movement, vigorous activity, and when rolling over in bed. Most round ligament pregnancy pain is experienced on the right side of the body, though it can occur on the left, as well.
While relaxin drops significantly after you give birth, you will have elevated levels of it for several months after your delivery different sources estimate it to take between five and twelve months for relaxin levels to go back to normal , which can continue to affect your body. For example, relaxin and weight gain may be responsible for your feet growing up to one full shoe size and your feet arches flattening.
Beyond that, relaxin will also cause your joints and ligaments to remain extra flexible and loose even after your pregnancy. This means that you may be more susceptible to injuries, as your musculoskeletal system is in a less stable state. As a result, you will want to be extra careful with exercising after giving birth. While you may be interested in activities such as yoga or pilates postpartum as a gentle post-pregnancy workout plan, you should take care to avoid overstretching.
After you have your baby, chances are you will experience some degree of abdominal separation, or so called Diastasis Recti. Relaxin, which loosens and weakens your core muscles, still stays in your body for a while after pregnancy. While your body will start to repair some of the abdominal separation on its own, you should pay close attention to this and look into core strengthening exercises to avoid long-term complications.
Learn more : Diastasis Recti symptoms and how to treat it. Some sources report that relaxin levels remain elevated in the body postpartum as long as a woman is breastfeeding and even for several months afterwards. It is also believed that the hormone may have an effect on the growth of the milk-producing tissue of the breasts and, indeed, relaxin is present in breast milk.
If you are breastfeeding, you may find that the joint-loosening effects of relaxin persist longer than they would if you were not breastfeeding, so breastfeeding mums are advised to take extra care with postpartum exercise until after they cease breastfeeding. Here are some tips for managing the more painful effects of relaxin. If your pelvic pain is particularly severe, physical therapy might be a good solution.
Arrows indicate time of delivery. The profile of serum relaxin in the pig differs from that in the rat throughout most of the d gestation period Fig. Relaxin rises gradually from about 0. The placenta is the source of the rapidly rising levels of estrogen during late pregnancy in pigs.
The profile of serum relaxin levels during human pregnancy 89 , 90 differs markedly from those in the rat, mouse, and pig in three ways Fig.
First, the profile of serum relaxin levels follows that of human chorionic gonadotropin: it is highest during the first trimester when the corpus luteum is most active, and it declines throughout the remainder of pregnancy.
Finally, because relaxin does not accumulate in human luteal cells as pregnancy progresses 92 and functional luteolysis does not occur, there is no antepartum surge in serum relaxin levels. Whereas the corpus luteum remains the source of circulating relaxin H2 relaxin throughout the approximately wk pregnancy 2 , the placenta becomes the dominant source of progesterone and estrogen during the second and third trimesters of human pregnancy 2.
Secondary sources of R1, M1, P1, and H2 relaxin that may produce sufficient hormone to act locally in a paracrine manner have been identified in reproductive and nonreproductive tissues 2 , 11 , 42 , Because the well-documented effects of relaxin are attributable to circulating luteal relaxin, potential actions of relaxin in other sources are given limited attention in this review.
Two pure hormone preparations were administered for essentially all studies. Purified porcine P1 relaxin 94 was used for in vivo studies in pigs, and rH2 relaxin was used for clinical investigations in humans.
Despite the marked differences in their primary structures, both P1 relaxin and rH2 relaxin have high and similar bioactivity in vivo in rodents 2 , Moreover, both hormones appear to be equally effective in in vitro systems using either rodent or human cells, tissues, and organs 2 , 50 , 65 , 71 , 72 , 74 , 78 , 80 , Section II describes the effects of relaxin on five female reproductive processes. Bagnell et al. Moreover, they found that low doses of P1 relaxin promote growth of both granulosa and theca cells in vitro — Consistent with these findings, specific relaxin-binding sites were localized in both the theca and granulosa cells of developing follicles There is also limited evidence that relaxin may act locally to promote follicular development and ovulation in rats.
Proteinase enzymes, including plasminogen activator and collagenase, play an essential role in bringing about the extracellular matrix remodeling required for follicular development and ovulation, and it was demonstrated that P1 relaxin promotes the secretion of these and possibly other proteinases from primary cultures of rat granulosa cells and theca-interstitial cells , Additionally, it was reported that rH2 relaxin induces ovulation in the in vitro perfused rat ovary , and that passive immunization of circulating R1 relaxin with a monoclonal antibody for R1 relaxin designated hereafter as MCA1 reduces the number of ovulated oocytes when immature rats are induced to superovulate with gonadotropins Studies in mice do not support a role for relaxin in either follicular development or ovulation.
P1 relaxin did not increase follicular growth or antrum formation in cultures of mouse preantral follicles Female mice without either a functional M1 relaxin gene or a functional LGR7 relaxin receptor gene are fertile, and the average litter size does not differ from that of controls 10 , A role for M3 relaxin cannot be ruled out because its gene is expressed in ovaries of nonpregnant mice Additionally, one must be mindful that differences exist in the actions of relaxin among species.
It remains to be demonstrated that endogenous relaxin plays a role in either follicular growth or ovulation during normal estrous cycles in any species. In the s Hisaw and co-workers examined the influence of prolonged administration of progesterone, estrogen, and partially purified P1 relaxin on the histological characteristics of the endometrium in juvenile or ovariectomized rhesus monkeys.
The finding that relaxin promoted growth of the endometrium, which included proliferation of the endothelial cells located in the distal portions of the spiral arteries, led these workers to postulate that one of the functions of relaxin is to assist in the preparation of the endometrium for implantation. A recent clinical trial in women with diffuse scleroderma provided additional evidence that relaxin may promote angiogenesis in the human endometrium. During the course of 24 wk of continuous sc infusion, women receiving rH2 relaxin reported heavy, irregular, or prolonged menstrual bleeding more often than women receiving a placebo Studies that used either P1 relaxin or rH2 relaxin with primary cultures of normal human endometrial cells demonstrated that relaxin binds with high affinity and specificity and increases the expression of hormones, growth factors, and other molecules associated with either decidualization, angiogenesis, or other processes at implantation in humans and other species.
Employing cultures of stromal cells, Tseng and co-workers 2 , demonstrated relaxin exerts a synergistic effect with progestin on the expression of prolactin, aromatase activity, estrone sulfate sulfatase, and IGF-binding protein-1, which is a major protein synthesized and secreted by decidualized cells.
Vascular endothelial growth factor VEGF , which has been implicated in the new vessel growth and vasodilation that occur in the endometrium at implantation , increases with the addition of relaxin to cultures of human endometrium stromal and epithelial cells , , Glycodelin, a glycoprotein produced and secreted by the secretory endometrium, has been postulated to contribute locally to immunosuppression at implantation Stewart et al.
It was also reported that P1 relaxin promotes the expression of glycodelin mRNA and protein in primary cultures of human endometrial epithelial cells There is also limited evidence that relaxin increases immunostaining for cyclooxygenase-2 and inhibits the expression of collagenase in primary cultures of human endometrial cells.
Relaxin appears to mediate its effects on human endometrial stromal cells, at least in part, through the generation of cAMP — There is limited evidence that relaxin acts in concert with estrogen and progesterone to enhance the expression of Hoxa, an endometrial transcription factor that is required at implantation in mice There have been a few in vivo studies of the effects of relaxin on the endometrium in estrogen or estrogen plus progesterone-primed nonpregnant primates and rodents.
Porcine relaxin in concert with estrogen was reported to increase endometrial thickness, number of glands, blood vessel content, and VEGF expression in ovariectomized nonpregnant marmosets Similarly, P1 relaxin was reported to promote increased endometrial thickness, loosening of collagen framework, and dilation of blood vessels in rats and mice , Finn et al.
If relaxin plays a role at implantation, it must be available to the uterine endometrium in quantities sufficient to be effective. Relaxin levels then rise in close association with chorionic gonadotropin in conceptive cycles , A clinical observation makes it seem unlikely that circulating relaxin is important at implantation in humans.
Women who experience premature ovarian failure can become pregnant through ovum donation. Implantation occurs in these women despite the fact that they have neither a corpus luteum nor detectable serum relaxin levels The possibility that luteal relaxin contributes to implantation cannot be ruled out for primates. In the marmoset, a New World monkey, serum relaxin levels rise a few days before implantation, and they are higher than in humans and Old World monkeys At present, little is known concerning the amounts, regulation, and function of endometrial relaxin in any species.
The fact that these animals are fertile, and the average litter size does not differ from that of wild-type controls 10 , 59 , indicates that M1 relaxin is not essential at implantation in mice. As with ovulation, it remains to be demonstrated that relaxin plays a role at implantation in any species. Studies conducted in pregnant rats and pigs provide convincing evidence that endogenous relaxin produces physiological effects between implantation and parturition. Relaxin affects 1 uterine growth and development, 2 myometrial contractility, 3 central regulation of plasma osmolality, 4 cardiovascular adaptations, and 5 the fetus.
With some effects, differences have been demonstrated among species. There is presently no evidence that relaxin is required to maintain pregnancy in any species. The average litter size in rats, mice, and pigs that are devoid of either circulating bioactive relaxin 10 , — or relaxin receptors 59 during the second half of pregnancy does not differ from that of controls.
Also, women who become pregnant with ovum donation maintain their pregnancies despite the fact that relaxin is not detectable in the circulating blood The physiological importance of the effects of relaxin between implantation and parturition remains to be demonstrated. The administration of P1 relaxin promotes growth of the uterine myometrium and endometrium in nonpregnant rodents and pigs 2 , — The uterotropic effects of relaxin are markedly influenced by estrogen.
Moreover, when ovariectomized pigs are treated with P1 relaxin for prolonged periods of 10 and 14 d chronic period , the hormone fails to have a significant effect on uterine growth in the absence of estrogen priming , The mechanism s whereby relaxin and estrogen act in combination to promote uterine growth remains poorly understood.
Estrogen may up-regulate relaxin receptors 2 , , There is also evidence that the acute effects of relaxin on the rat uterus are mediated through ligand-independent activation of the estrogen receptor Progesterone also influences the effects of relaxin on uterine growth in rats and pigs, but the influence of progesterone may differ in the two species. Whereas progesterone inhibited acute relaxin-induced increases in uterine wet weight and collagen content in ovariectomized prepubertal rats , progesterone augmented both the acute and chronic uterotropic effects of relaxin in ovariectomized gilts.
The discovery that relaxin has marked effects on growth and development of the uterus in nonpregnant rats and pigs led to the hypothesis that endogenous relaxin plays a role in accommodating the developing fetuses during pregnancy 2.
Experimentation did not support the hypothesis in pregnant rats and mice, but did in pigs Fig. When circulating R1 relaxin was neutralized with monoclonal antibody MCA1 throughout the second half of rat pregnancy, the uterus was as large at term in relaxin-deficient animals as in controls Consistent with this finding, uterine wet and dry weights increased as dramatically during pregnancy in M1RKO mice as they did in wild-type controls Influence of deprivation of endogenous relaxin during pregnancy on the wet weight of the uterus, cervix, and vagina at term pregnancy.
Left , Rat [Compiled from J. Hwang and O. Sherwood: Endocrinology —, Kuenzi and O. Zhao et al. Zhao and O. Middle , Mouse [Adapted from L. Right , Pig [Reprinted with permission from G. Min et al. Numerous in vivo or in vitro pharmacological studies employed nonpregnant animals to demonstrate that either P1 relaxin or rH2 relaxin reduces the frequency of myometrial contractions in several species, including rats, mice, and pigs 2. In rats and pigs, myometrial activity is low when serum relaxin levels are elevated, and then it increases markedly at delivery — When rats were ovariectomized on d 9 of pregnancy and given hormone replacement therapy with physiological levels of progesterone and estrogen throughout the remainder of pregnancy, the frequency of intrauterine pressure cycles remained well above that in intact controls.
In contrast, when hormone replacement therapy included both steroids and P1 relaxin, the frequency of intrauterine pressure cycles declined to levels that did not differ from those in controls Fig. Influence of endogenous relaxin on uterine contractility in pregnant rats. Downing and O. Other hormones, including progesterone, estrogen, oxytocin, and prostaglandins, have direct actions on the myometrium during pregnancy, and the interaction of relaxin with these hormones is only beginning to be understood.
Progesterone plays an essential role in maintaining pregnancy by providing hormonal support for the endometrium and preventing strong, highly coordinated uterine contractions. There is in vitro evidence that progesterone increases the sensitivity of the myometrium to the quiescent effect of relaxin in rats and pigs — Studies in ovariectomized nonpregnant rats demonstrated that estrogen also markedly increases the sensitivity of the myometrium to the quiescent effect of relaxin 2 , 22 , , and it may do so by inducing the formation of relaxin receptors , , — Numerous studies in rats and pigs provide evidence that pharmacological doses of relaxin inhibit myometrial contractions induced by either oxytocin or prostaglandin 2.
However, it is not presently known whether endogenous relaxin prevents or diminishes contractions induced by oxytocin or prostaglandins before delivery. It is known that under normal physiological conditions at term pregnancy, potent and highly coordinated contractions of the myometrium occur in rats and pigs despite moderate levels of relaxin in the serum. The mechanisms regulating uterine contractility and their hormonal control by relaxin, oxytocin, and other hormones are complex and partially understood 2 , 22 , — Fig.
The activated MLCK phosphorylates the kDa regulatory chain of myosin and thereby enhances the interaction of myosin with actin and actin-activated myosin ATPase to bring about contraction.
Relaxin treatment blocks the above cascade of events. The actions of relaxin on myometrial cells are only partially mediated through activation of PKA 2 , 22 , , Also inconsistent are reports that relaxin may up-regulate the l -arginine-nitric oxide pathway to increase the second messenger cGMP, thereby inhibiting uterine smooth muscle contractility 2 , 80 , Intracellular mechanisms whereby relaxin and oxytocin regulate contractions of uterine myometrial cells.
Possible effects of relaxin that have not been demonstrated are shown with dashed arrows. Ion channels that control influx of calcium at the level of the plasma membrane are capacitated calcium entry CCE and voltage-operated VOC.
Sanborn et al. Relaxin also attenuates the contractile effects of oxytocin on human myometrial cells. The PLC stimulates phosphoinositol 4,5-bisphosphate turnover and production of inositol triphosphate IP 3 and diacylglycerol.
Studies that employed P1 relaxin with immortalized pregnant human myometrial cells provide evidence that relaxin inhibits the effects of oxytocin through activation of PKA. This is probably an oversimplification. Kuznetsova et al. A physiological role of relaxin on human myometrial contractility remains to be demonstrated. Whereas relaxin induces responses in human myometrial cells, there is limited evidence that relaxin does not inhibit contractions of human uterus in vitro 2 , 22 , Plasma osmolality is maintained within a narrow range by a complex interaction between thirst mechanisms, neurohypophysial release of vasopressin, and the actions of this antidiuretic hormone on the kidney Studies in humans and rats demonstrated that during pregnancy there is an approximately 10 mosmol decline in plasma osmolality that occurs without a change in plasma vasopressin concentrations, and this adaptation of pregnancy is attributable to a reduced osmotic threshold for both thirst and vasopressin secretion There is evidence that relaxin contributes to the decline in plasma osmolality that occurs during pregnancy in rats and mice.
Plasma osmolality in nonpregnant rats declined about 10 mosmol after the infusion of either rH2 relaxin or P1 relaxin for 5 or 6 d 19 , , In pregnant rats, a reduction in plasma osmolality coincides with the elevation in serum relaxin levels during the second half of pregnancy 82 , When pregnant rats were made R1 relaxin deficient by either passive immunization with monoclonal antibody MCA1 or ovariectomy, a reduction in plasma osmolality failed to occur Consistent with findings in rats, plasma osmolality during late pregnancy in M1RKO mice is about 10 mosmol higher than in wild-type controls Relaxin may not contribute to the reduction of plasma osmolality that occurs during pregnancy in humans.
Plasma osmolality was reported to fall and not differ from that in normal controls in women with singleton pregnancies after ovum donation despite the fact that they have undetectable serum relaxin , The effects of relaxin on the osmotic threshold during pregnancy are probably mediated, at least in part, through its central effects on drinking and vasopressin secretion from the posterior pituitary.
This hypothesis has been examined only in rats. Water consumption increases markedly during the second half of rat pregnancy — , and two lines of evidence indicate that relaxin stimulates drinking during this period through actions on the brain.
Either intracerebroventricular icv or iv administration of relaxin promotes drinking within minutes in nonpregnant rats — Second, when passive immunization with monoclonal antibodies for R1 relaxin was used to remove relaxin from either the peripheral circulation or icv fluid throughout the second half of rat pregnancy, water consumption was reduced.
Moreover, the reduction in drinking was most profound when relaxin was neutralized in the icv fluid Whereas plasma osmolality declines during pregnancy in rats, blood levels of vasopressin do not change significantly Perhaps relaxin acts centrally to contribute to the phenomenon. Either icv or iv administration of P1 relaxin causes secretion of vasopressin in anesthetized nonpregnant rats 15 , — One can speculate that by acting centrally, endogenous relaxin contributes to the reduced osmotic threshold for vasopressin secretion that occurs during rat pregnancy.
By maintaining serum concentrations of vasopressin that are similar to those of nonpregnant rats, water retention is promoted in the renal collecting ducts in pregnant rats despite plasma osmolality that would markedly reduce vasopressin secretion in nonpregnant rats. At this time, however, the central effects of endogenous relaxin on vasopressin secretion in pregnant rats have not been demonstrated.
Relaxin appears to initiate its effects on drinking and vasopressin secretion in rats through actions on the subfornical organ SFO and organum vasculosum of the lamina terminalis OVLT , two circumventricular organs located on the anterior wall of the third cerebral ventricle that lack a blood-brain barrier and are accessible to circulating relaxin Fig.
Additionally, after iv administration of either P1 relaxin or rH2 relaxin, the expression of c -fos increased in groups of neurons located in the more peripheral and dorsal parts of the SFO and in the dorsal cap region of the OVLT , , — Diagram of actions of blood-borne relaxin or systemic hypertonicity on the circumventricular organs of the lamina terminalis to influence body fluid homeostasis.
MnPO, Median preoptic nucleus. McKinley et al. The SFO and OVLT probably mediate the central actions of relaxin, at least in part, by activating efferent pathways projecting to the paraventricular PVN and supraoptic SON nuclei, the magnocellular hypothalamic sites that produce vasopressin and oxytocin.
There are both direct and indirect neural pathways from the circumventricular organs to the hypothalamic nuclei that produce vasopressin and oxytocin. Summerlee and Wilson reported that radiofrequency lesions of the SFO on d 12 of pregnancy reduced the rate of increase in water consumption during the second half of pregnancy. These workers postulated the OVLT may stimulate vasopressin secretion Osmosensitive neurons reside in the dorsal cap of the OVLT, where enhanced c -fos expression is observed after relaxin administration.
Because these OVLT neurons have efficient projections to the SON, they could be the neuroanatomical site where relaxin resets the osmostat during pregnancy , There is evidence that the neuronal pathways originating in the SFO and OVLT that mediate the effects of relaxin on drinking and vasopressin secretion do so by utilizing angiotensin produced within the brain as a neurotransmitter that acts through angiotensin 1 receptors , , , , During human pregnancy, cardiovascular adaptations that are observed by 5—8 wk include not only increased plasma volume, cardiac output, and heart rate but also decreased blood pressure and vascular resistance , Similar cardiovascular changes occur relatively later in rat pregnancy , , Recent studies provide evidence that relaxin may contribute to cardiovascular adaptations during pregnancy through effects on the kidney, vasculature, and heart.
Conrad and co-workers 19 and Conrad and Lindheimer postulated that the circulations of nonreproductive organs such as the kidney serve as arteriovascular shunts that bring about a fall in ventricular afterload during pregnancy. The decrease in ventricular afterload initiates the increase in cardiac output and expansion of plasma volume that occurs during rat and human pregnancy.
In pregnant rats, glomerular filtration rate and effective renal plasma flow increase whereas effective renal vascular resistance declines 19 , and these renal adaptations are maximal during the second half of pregnancy when serum relaxin levels are elevated. The above renal adaptations of pregnancy failed to occur when circulating R1 relaxin was neutralized with monoclonal antibody MCA1 Relaxin may play a role in these adaptations of pregnancy through direct effects on the vasculature.
Conrad and co-workers 18 , 19 , , demonstrated that relaxin is a potent renal vasodilator in rats, promoting both a reduction in myogenic reactivity of small arteries and attenuation of the vasoconstrictive response of the vasculature to angiotensin II. There is evidence that relaxin up-regulates endothelin type B receptors on the vascular endothelium and also the release of nitric oxide, a potent vasodilator 18 , 72 , , Findings indicate that this vascular gelatinase acts upstream of, and in series with, the endothelial endothelin type B receptor-NO signaling pathway.
It appears to do so by processing big endothelin 1 to endothelin-1 1— In rats, there is a small reduction in blood pressure during midpregnancy and a larger decline during the 2 or 3 d that precede delivery , , It is conceivable that endogenous circulating relaxin contributes to this decline in blood pressure.
Relaxin has been reported to dilate not only microvessels such as arterioles that are surrounded by a smooth muscle coat but also capillaries and postcapillary venules in numerous sites throughout the body.
In rodents, relaxin promotes dilation of microvessels in not only reproductive organs , , , but also in nonreproductive sites, in addition to the kidney described above, including the heart 79 , , , liver , and mesocecum Relaxin has also been reported to blunt responses to vasoconstrictors in perfused mesenteric artery of spontaneously hypertensive rats , , primary cultures of bovine aorta smooth muscle cells 73 , rat coronary endothelial cells 74 , and segments of rat uterine artery As in the kidney, relaxin appears to mediate its effects on vasodilation in mesenteric arteries and other sites, at least in part, by acting on endothelial cells to up-regulate endothelin type B receptors and also to stimulate the activity of inducible nitric oxide synthase II, thereby increasing nitric oxide production 18 , 72 , 74 , 79 , , , , The connection between these two pathways in relaxin signal transduction, if any, remains to be elucidated.
It is possible that relaxin does not promote vasodilation in all blood vessels. Whereas in vitro treatment with rH2 relaxin was reported to cause a rapid relaxation of human preconstricted gluteal arteries in an endothelium-dependent manner, it did not influence small pulmonary resistance arteries, uterine myometrial arteries, or placental stem villus arteries , Moreover, the hormone does not appear to play a role in the antepartum decline in blood pressure in rats.
Acute iv administration of relaxin during late pregnancy did not influence blood pressure in conscious rats or anesthetized rats Moreover, removal of endogenous relaxin by either bilateral ovariectomy or by passive immunization of endogenous relaxin 19 failed to influence mean arterial pressure in pregnant rats.
Consistent with this finding, short-term infusion of rH2 relaxin had no effect on blood pressure in pregnant rhesus monkeys The heart is a target organ for relaxin. Sites that bind radiolabeled rH2 relaxin with high affinity and specificity were reported in rat atria , , , , and mRNA for the relaxin receptor LGR7 was also identified in the rat 57 , 58 , mouse 59 , and human 12 heart. Numerous in vitro studies have shown that relaxin has potent, direct and concentration-dependent chronotropic and inotropic effects on the isolated rat heart.
Relaxin increased not only the rate of spontaneous contractions in perfused intact hearts , — and isolated right atria 20 , 21 , 48 , , but also the force of electrically stimulated contractions in isolated left atria 20 , 21 , 48 , , Relaxin may act on both atrial and ventricular pacemakers because relaxin increased heart rate in heart preparations in which the atria had been removed The signal transduction pathways whereby relaxin enhances contractility of the heart have received limited experimental attention.
When individual cells were examined with whole-cell patch clamp, relaxin was found to inhibit outward potassium currents, increase action potential duration, and enhance calcium entrance into rat atrial myocytes , In similar experiments, relaxin increased the rate of action potentials and L-type calcium current in rabbit sinoatrial node cells These effects involved the activation of PKA — Does endogenous relaxin influence heart contractility in intact pregnant rats?
Acute iv or icv administration of P1 relaxin increased heart rate in urethane-anesthetized nonpregnant rats , , , and infusion of rH2 increased heart rate in unanesthetized nonpregnant rats However, acute arterial administration of rH2 relaxin on d 19 did not influence heart rate in conscious pregnant rats The effect, if any, of endogenous circulating relaxin on heart rate in pregnant rats has not been reported.
Interestingly, the central and cardiovascular effects of relaxin appear to be as profound in male as in female rodents. In males, relaxin was reported to decrease plasma osmolality and increase drinking , , , , vasopressin secretion , glomerular filtration rate, effective renal plasma flow , vasodilation — , and heart rate 20 , 21 , There is evidence that circulating maternal relaxin influences fetal development during rat pregnancy.
When rats were deprived of circulating relaxin throughout the second half of pregnancy by either immunoneutralization of R1 relaxin with monoclonal antibody MCA1 or ovariectomy, fetal weights were significantly greater than in controls , , — It is not known whether this enlargement of fetuses is attributable to the effects of relaxin deprivation on the mother or on the fetus.
It does appear likely that only small amounts of maternal relaxin pass to the fetal serum. Whereas serum levels of relaxin in rat fetuses are not known, those in hamster and human fetuses were reported to be low and nondetectable , , respectively. Consistent with this view are reports of transplacental passage of small amounts of rH2 relaxin in pregnant rhesus monkeys , Again, one must be mindful of possible differences among species.
An influence of circulating maternal relaxin on fetal weights was not observed with either M1RKO mice or ovariectomized pigs There is also limited evidence that relaxin contributes to testicular descent during late rat pregnancy , and that will be described in more detail in Section III.
The preponderance of data indicates that circulating endogenous relaxin does not influence the duration of pregnancy. The time of onset of delivery in rats in which circulating R1 relaxin was immunoneutralized with monoclonal antibody MCA1 , and in mice that lacked either a functional relaxin gene 10 or relaxin receptor LGR7 gene 59 did not differ from that of controls.
There is one report that is not consistent with these findings. When the soluble ligand-binding portion of the human relaxin receptor LGR7 was administered sc to antagonize endogenous circulating relaxin the last 4 d of mouse pregnancy, delivery was delayed by 27 h The onset of both luteolysis and delivery was advanced approximately 24 h after central immunoneutralization of relaxin by daily injection of monoclonal antibody for R1 relaxin into the right lateral ventricle throughout the second half of pregnancy It was postulated that central R1 relaxin may influence the time of delivery by acting on the SFO to inhibit oxytocin secretion , There are observations that are not consistent with this hypothesis.
Intravenous administration of P1 relaxin increased the secretion of oxytocin in unanesthetized nonpregnant and pregnant rats , Moreover, neither the time of onset nor the duration of active labor in oxytocin knockout mice differed from those of wild-type controls Two experimental approaches demonstrated that circulating relaxin has vital effects at parturition in rats and pigs.
When primiparous rats and pigs were bilaterally ovariectomized during the second half of pregnancy and given hormone replacement with physiological amounts of progesterone plus estrogen rats or progesterone only pigs , the duration of delivery was several times longer, and the incidence of live births was far lower than in intact controls , , , However, when hormone replacement included physiological levels of P1 relaxin, birth parameters were similar to those of controls , , Comparable findings were obtained in both rats , , and pigs when circulating relaxin was immunoneutralized Fig.
Influence of immunoneutralization of circulating R1 relaxin throughout the second half of rat pregnancy on delivery. Lao Guico-Lamm and O. Recent studies with pregnant M1 relaxin knockout and relaxin receptor LGR7 knockout mice indicate that relaxin is also required for normal delivery in mice. Two of eight M1RKO mice were unable to deliver their pups normally. Moreover, in one of the mice, all pups were either stillborn or died in utero during parturition Similarly, 25 of pups distributed among nine of 21 litters born of LGR7KO mice were found dead on the morning of delivery Relaxin deficiency does not disrupt delivery as dramatically in mice as it does in rats and pigs.
At present, there is no solid evidence that endogenous relaxin facilitates delivery in humans. Circulating levels of relaxin are so low Fig. Available evidence supports the view that the primary means whereby relaxin facilitates birth in rats, mice, and pigs is by promoting dramatic growth and remodeling of the cervix. The effects of relaxin on two other portions of the birth canal—the vagina and the interpubic ligament—may also play roles at the time of delivery in some species.
We'll cover relaxin first. Your ovaries and the placenta produce relaxin. Relaxin levels are typically highest during the first trimester because they prevent your body from having contractions that can lead to premature birth.
This pregnancy hormone also loosens the ligaments in your pelvis. Unfortunately, relaxin is nondiscriminatory about the ligaments it loosens, so it affects all the joints and ligaments in your body. This loosening can lead to lower back and hip pain, which is very common during pregnancy. Toward the end of your pregnancy, relaxin gets to work softening and widening your cervix.
Like relaxin, oxytocin works to prepare your cervix for birth. Oxytocin achieves this by creating strong contractions in your body. Once your little one arrives, oxytocin also causes the milk to release during breastfeeding. Pregnancy hormones can make your life miserable, with nausea, joint and back pain, and even those frequent trips to the bathroom.
It's thanks to your hormones, though, that your body is able to grow that little human inside you. Prenatal screening tests are a great way to make sure your pregnancy hormones are functioning as they should. Learn more about the screening tests NTD Eurofins offers — then ask your doctor about which tests can help you plan for a healthy, happy baby.
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