Relaxin Secretion in the Rhesus Monkey1

Weiss, Gerson; Steinetz, Bernard G.; Dierschke, Donald J.; Fritz, G. R.

doi:10.1095/biolreprod24.3.565

Cited by 25 publications

(17 citation statements)

References 10 publications

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“…In rodents and guinea pigs, relaxin significantly increases the intrapubic ligament to enlarge the diameter of the pubis (2-4). This is not seen in primates (2,8,9).…”

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confidence: 90%

“…In rodents and guinea pigs, relaxin significantly increases the intrapubic ligament to enlarge the diameter of the pubis (2-4). This is not seen in primates (2,8,9).In women, the source of circulating relaxin is the ovarian corpus luteum (11). Relaxin is detectable in maternal circulation during the late luteal phase of the menstrual cycle.…”

mentioning

confidence: 99%

“…Relaxin is necessary for normal delivery in pigs, which also have a major prepartum relaxin surge not seen in primates (7)(8)(9). In horses and rabbits, the placenta is the major source of relaxin, not the ovary (2,3,10).…”

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confidence: 99%

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Relaxin regulation of endometrial structure and function in the rhesus monkey

Goldsmith

Weiss

Palejwala

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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Despite the documented importance of the protein hormone relaxin in reproduction in various mammalian species, the role of relaxin in human reproduction is poorly understood, largely because of the lack of studies in women or in suitable non-human primate models. Here we describe the establishment of a nonhuman primate model of early human pregnancy and its use in defining the actions of relaxin. Results demonstrate that relaxin exerts dramatic uterine effects including pronounced increase in uterine weight and stimulation of endometrial angiogenesis and resident endometrial lymphocyte number. In addition, relaxin decreases endometrial levels of matrix metalloproteinases 1 and 3 and increases levels of their endogenous inhibitor, tissue inhibitor of metalloproteinase 1, resulting in maintenance of endometrial collagen content. Relaxin significantly inhibits endometrial levels of estrogen receptor ␣, but not ␤, and of progesterone receptor isoforms A and B. The findings that relaxin stimulates new blood vessel formation and increases cytokine-containing lymphocyte number while maintaining endometrial connective tissue integrity are consistent with a significant role of relaxin in the establishment and͞or maintenance of early pregnancy.R elaxin is a 6-kDa protein hormone member of the insulinlike growth factor family present in circulation in women during the latter part of the menstrual cycle and throughout pregnancy (1). In many mammalian species, relaxin exerts pronounced effects on the female reproductive tract that are involved in the maintenance of pregnancy and successful parturition (2, 3). Relaxin is important for normal delivery in several mammalian species because of its marked rearrangement of reproductive tract connective tissue (2-4). Despite the documented importance of relaxin in various mammalian species, the role of relaxin in human reproduction is, to date, an important, yet unanswered, question. Elucidation of the role of relaxin in women has been hampered by the inability to perform studies in women and by the lack of studies performed in suitable primate models of human pregnancy. Here we describe the establishment of a non-human primate model of early human pregnancy and its use in defining the actions of relaxin. Results demonstrate that relaxin exerts dramatic uterine effects including pronounced increase in uterine weight, stimulation of endometrial angiogenesis and resident lymphocyte number, maintenance of endometrial connective tissue integrity, and inhibition of endometrial estrogen and progesterone action. These effects are the developmental changes that occur in the human uterus during the late secretory phase of the menstrual cycle and early pregnancy. These findings support the thesis that relaxin acts as an important factor in uterine accommodation to and maintenance of early pregnancy in women.The dramatic species differences in the sources, secretion patterns, and target organs of relaxin have contributed greatly to the lack of understanding of the role of relaxin in human repr...

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“…In rodents and guinea pigs, relaxin significantly increases the intrapubic ligament to enlarge the diameter of the pubis (2-4). This is not seen in primates (2,8,9).…”

mentioning

confidence: 90%

mentioning

confidence: 99%

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Relaxin regulation of endometrial structure and function in the rhesus monkey

Goldsmith

Weiss

Palejwala

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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“…This RIA has been routinely used for determination of relaxin in human plasma during pregnancy in women [8] and monkeys [9]. The assay utilizes rabbit anti-porcine relaxin antiserum R6 that has been shown to cross-react with relaxins of many different species.…”

Section: Radioimmunoassays (Rias)mentioning

confidence: 99%

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).

Shimizu

Wei

Kishi

et al. 2002

Journal of Reproduction and Development

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Abstract. Effects of intracervical prostaglandin E2 (PGE2)-gel treatment on ripening of the cervix at term pregnancy were investigated. Concentrations of relaxin, LH estradiol-17 β 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-17 β 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-17β may be involved in ripening of the cervix without increasing circulating relaxin during the period of PGE2-gel treatment in the Japanese monkey. Key words: Relaxin, Japanese monkey, Prostaglandin E2, Pregnancy, Cervix (J. Reprod. Dev. 48: [607][608][609][610][611] 2002) lthough softening and dilatation of the cervix t o ge t h er w i t h ut er i n e c o n t r a c t i o n s a r e necessary for parturition, the exact mechanism of the onset of labor remains to be determined in the Japanese monkey. A dramatic change in the structure and function of the myometrium and cervix are regulated by the co mbination of estrogen, progesterone, prostaglandins, oxytocin and relaxin during pregnancy and labor. Some of them have been used to promote cervical ripening before the induction of labor to increase the success rate of induction and shortening the delivery time.In our previous study, intracervical administration of prostaglandin E2-gel (PGE2-gel) induced cervical ripening and stimulated uterine contraction without induction of labor at term pregnancy in the Japanese monkey [1]. Moreover, previous studies have demonstrated that exogenous prostaglandins precipitated premature delivery or abortion when administrated to pregnant rhesus monkeys and women [2].Relaxin is a polypeptide hormone found in the blood of pregnant mammals [3] and is known for its actions on the smooth muscle of the uterus and connective tissue of the pubis symphysis and cervix d u r i n g p r e g n an c y [ 4 ]. W e h a v e r e c e n t l y

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“…Secretory patterns of relaxin have been reported in rodents, pigs, women [3] and a few nonhuman primates, including chimpanzees [4], baboons [5], rhesus monkeys [6], cynomolgus monkeys [7] and common marmosets [8]. In rodents and pigs [3], immunoreactive relaxin rises to a peak shortly before parturition and is correlated with the increase in cervical dilatability and formation of an interpubic ligament.…”

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confidence: 99%

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

Shimizu

Wei

Kishi

et al. 2002

Journal of Reproduction and Development

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Abstract. 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. Key words: Relaxin, Japanese monkey, Pregnancy, Parturition, Lactation (J. Reprod. Dev. 48: [383][384][385][386][387][388][389][390][391] 2002) elaxin is a polypeptide hormone found in the serum of pregnant mammals [1], and is known to assist the maintenance of pregnancy and the preparation of the reproductive tract for parturition in mammalian species [1]. Furthermore, it has been reported that relaxin is involved in the growth of the mammary gland during pregnancy, at the onset of lactation, and in established lactation [2]. , immunoreactive relaxin rises to a peak shortly before parturition and is correlated with the increase in cervical dilatability and formation of an interpubic ligament. In women, relaxin is detectable from the time of missed menses, is highest in the first trimester, and gradually declines thereafter until delivery, without a prelabor surge

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Relaxin Secretion in the Rhesus Monkey1

Cited by 25 publications

References 10 publications

Relaxin regulation of endometrial structure and function in the rhesus monkey

Relaxin regulation of endometrial structure and function in the rhesus monkey

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).

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

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