Relaxin affects the central control of oxytocin release

Summerlee, A. J. S.; O’Byrne, Kevin; Paisley, A.C.; Breeze, M. F.; Porter, D. G.

doi:10.1038/309372a0

Cited by 85 publications

(59 citation statements)

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“…In addition to its classical actions on cervical ripening, uterine contraction, and pubic symphysis elongation (1,2), relaxin has been suggested to participate in the regulation of blood pressure (3)(4)(5)(6)(7)(8) and neuropeptide release, notably oxytocin and vasopressin (9)(10)(11)(12)(13). However, the results from these studies were conflicting, and the site of action of relaxin was undetermined.…”

mentioning

confidence: 78%

Relaxin binding in the rat heart atrium.

Osheroff¹,

Cronin²,

Lofgren³

1992

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

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Relaxin is a member of the insulin family of polypeptides that is best known as a reproductive hormone. In an effort to elucidate the mechanism of action of relaxin we previously localized the specific binding sites of a 32P-labeled relaxin in the rat uterus and brain. These studies suggested that, in addition to its classical role in pregnancy, relaxin might have other physiological functions. In the present paper we describe the specific and high-afminity binding of relaxin to the cardiac atrium of both male and female rats. The relaxin binding could not be displaced by peptides belonging to the same family [insulin, insulin-like growth factor I (IGF-I)] or by peptides that were identified in the atrium or were known to have cardiovascular functions (atrial natriuretic peptide, angiotensin II). The dissociation constant for relaxin in the atrium was estimated to be 1.4 nM, which was similar to that found in the uterus (1.3 nM) and the brain (1.4 nM). In view of the close association of relaxin with reproduction, an experiment was also performed to compare the relaxin binding in the uterus and heart after gonadectomy and sex steroid treatment. It was found that the relaxin binding in the rat uterus was diminished by 53% overall following ovariectomy but was restored to 90% of normal levels when treated with estrogen (but not with testosterone). In contrast, the relaxin binding in the rat heart was not affected by castration or sex steroid treatment. We conclude that specific and high-affinity relaxin receptors exist in the atrium of both the male and female rat heart and that these are regulated differently than the relaxin receptors in the uterus.Relaxin is structurally related to insulin and insulin-like growth factors and is best known as a pregnancy-associated hormone (1, 2). In addition to its classical actions on cervical ripening, uterine contraction, and pubic symphysis elongation (1, 2), relaxin has been suggested to participate in the regulation of blood pressure (3-8) and neuropeptide release, notably oxytocin and vasopressin (9-13). However, the results from these studies were conflicting, and the site of action of relaxin was undetermined. Biochemical support for these hypotheses was provided when it was shown that, in addition to the uterus and cervix (14), relaxin bound with specificity and high affinity (Kd 1 nM) to several sites in the male and female rat brain (15). Some of these sites, in particular two of the circumventricular organs (subfornical organ and organum vasculosum of the lamina terminalis) and the magnocellular hypothalamic nuclei (paraventricular and supraoptic nucleus) are known to be involved in the control of blood pressure, fluid balance, and the release of neuropeptides. To further investigate the mechanism of action of relaxin, we continued the search for relaxin target tissues and were surprised to observe the specific and high-affinity binding of relaxin to the atrium of the rat heart. We also show that the atrial binding is regulated differently than the uterus. ...

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confidence: 78%

Relaxin binding in the rat heart atrium.

Osheroff¹,

Cronin²,

Lofgren³

1992

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

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“…The first report that relaxin acted on the brain was provided by Summerlee and colleagues (19) who showed that porcine relaxin disrupted reflex milk-ejection in lactating rats. The critical evidence for an action at the level of the brain was provided by showing that the mammary gland in the relaxin-treated rats could still respond to exogenous oxytocin and was supported further by reports that relaxin inhibited electrically-stimulated release of oxytocin from the rat neurohypohysis in vivo (20).…”

Section: Relaxinmentioning

confidence: 99%

The Emerging Concept of Relaxn as a Centrally Actng Peptide Hormone with Hemodynamic Actions

Geddes

Summerlee

1995

J Neuroendocrinology

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The novel finding that relaxin has an action on the brain was first published in 1984. Since then, it has been shown that exogenous relaxin affects the release of a number of hypothalamo-pituitary hormones and has a robust pressor action. In this paper, we review the accumulating evidence that relaxin affects the release of oxytocin and vasopressin by an action at the level of the brain. The potential mechanisms of this central action are discussed and the evidence presented for the interaction between relaxin and the forebrain angiotensin-ll system. Furthermore, we articulate the possible physiological influences of relaxin on the changes in cardiovascular function that occur during pregnancy.F. L. Hisaw ( I ) discovered an ovarian substance that caused relaxation of the pelvic ligament of a variety of species in 1926 but it was not until 1930 that the first crude extract of the substance was obtained and named relaxin (2). Initial work focused on the role of relaxin on the birth canal and it was not until 1957 that an effect on the cardiovascular system was first reported (3). Miller and colleagues (3) showed that an extract of ovary caused a short hypotensive episode in dogs and suggested that relaxin had a direct action on peripheral blood vessels. Since that time. a number of hemodynamic actions of relaxin have been described (4, 5). The balance of the data, however, suggests that relaxin is hypertensive and exerts this effect through an action at the level of the brain (6-9) and on the heart (10, 11). RelaxinRelaxin is a peptide hormone produced primarily by the corpus luteum, placenta, uterus and possibly brain. It is present in detectable quantities in the peripheral circulation only during pregnancy. There are considerable species differences in the site and pattern of release of the hormone, hormone structure, and the putative role the hormone plays in the preparturient period. These differences have been extensively reviewed by Sherwood (4). Most research into the physiological actions of relaxin has been carried out using porcine relaxin obtained by the method described by Sherwood and O'Byrne (12). The classic actions of relaxin in pregnancy include softening of the cervix (13), separation of the pelvic symphysis (14). and maintenance of myornetrial quiescence towards the end of pregnancy ( 15).In the rat, relaxin is produced almost entirely within the corpora lutea of pregnancy (16) although there is some evidence that the hormone may also be produced by the endometrium (17). Levels of hormone are below the limit of detectability, by radioimmunoassay. during the first 7/12 days of pregnancy and start to increase from day 7 onwards. The levels increase steadily until day 16 when they begin to plateau. In the 48 h before birth, in association with the collapse of the corpora lutea, relaxin levels show a sharp peak then fall to low levels before birth starts (18). Sherwood et al. (18) also reported that there were peaks of relaxin in parturition. Although these data have not been confirmed by ...

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Section: Discussionmentioning

confidence: 99%

“…Thus, pelvic and cervical relaxation, Inhibition of uterine myometrial activity, and mediation of luteolysls may be due to very different and probably opposing mechanisms limited to specific endocrine and physiological states. Such a mechanism is possible, administration of relaxln (1 ug per rat) into the cerebral hemispheres profoundly disturbed the patterns of reflex milk let down without affecting the response of the mammsry gland to oxytocin (Summerlee et al, 1984). Changes and availability of relaxln and oxytocin receptor population during late pregnancy may change the effectiveness of relaxln as gestation advances.…”

mentioning

confidence: 99%

“…However, for a hormone which inhibits uterine myometrial activity and induces uterine quiescence presumably by inhibiting oxytocin release (Forter, 1984;, such a role requires relaxin to be able to affect two opposing phenomena. Relaxin affects the central nervous 109 system control of oxytocin release In rats (Summerlee et al, 1984).Both oxytocin and prostaglandin (PGF^^) can cause the release of relaxln in the pig Nara and First, 1981).Similarly, oxytocin and PGF^^ affect each other's release in the pig (Chan, 1977; Ellendorff et al, 1979; Flint and Sheldrick, 1983).The relatively low and steadily increasing peripheral concentrations of relaxln in the plasma of pregnant animals may inhibit uterine myometrial activity and oxytocin release. However, the precisely timed release of ovarian relaxln in pregnant and hysterectomized pigs (Felder et al, 1986) may have a different physiological bearing by probably inducing neurohypophysial oxytocin release.…”

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confidence: 99%

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Relaxin on induction of parturition in cattle: effects on hormonal, pelvic and cervical changes, and postpartum fertility

Musah

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This reproduction was made from a copy of a manuscript sent to us for publication and microfilming. While the most advanced technology has been used to pho tograph and reproduce this manuscript, the quality of the reproduction is heavily dependent upon the quality of the material submitted. Pages in any manuscript may have indistinct print. In all cases the best available copy has been filmed.The following explanation of techniques is provided to help clarify notations which may appear on this reproduction. Ï. Manuscripts may not always be complete. When it is not possible to obtain missing pages, a note appears to Indicate this.2. When copyrighted materials are removed from the manuscript, a note ap pears to indicate this. Oversize materials (maps, drawings, and charts) are photographed by sec tioning the original, beginning at the upper left hand comer and continuing from left to right in equal sections with small overlaps. Each oversize page is also filmed as one exposure and is available, for an additional charge, as a standard 35mm slide or in black and white paper format.* 4. Most photographs reproduce acceptably on positive microfilm or micro fiche but lack clarity on xerographic copies made from the microfilm. For an additional charge, all photographs are available in black and white standard 35mm slide format.* *Por more information about black and white slides or enlarged paper reproductions, please contact the Dissertations Customer Services Department. 'Uiii\vnuty PLEASE NOTE:In all cases this material has been filmed in the best possible way from the available copy. Problems encountered with this document have been identified here with a check mark V . lacking when material received, and not available from school or author.12. Page(s) seem to be missing in numbering only as text follows.13. Two pages numbered . Texi foiiows.14. Curling and wrinkled pages 15. Dissertation contains pages with print at a slant, filmed as received Other University Microfilms InternationalRelaxin on induction of parturition in cattle: Effects on hormonal, pelvic and cervical changes, and postpartum fertility Iowa State University Ames, Iowa 1986Signature was redacted for privacy.Signature was redacted for privacy.Signature was redacted for privacy.Signature was redacted for privacy.ii GENERAL INTRODUCTION IntroductionRelaxin is a polypeptide hormone produced primarily during pregnancy in several mammalian species. Hisaw (1926) receives credit for first discovering relaxin while working on the phenomenon of interpublc liga ment separation in rodents. Relaxin was overshadowed by progesterone, also produced by the corpora lutea, and remained obscure until the advent of protein purification and recombinant DNA technology during the last half decade. The amino acid sequences of relaxin from pig, rat, tiger shark, dogfish shark, and human have since been established. The hormone consists of two peptide chains (A and B) joined by disulfide bonds with an intrachaln disulfide bond in the A chain similar to insulin.Although r...

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Relaxin affects the central control of oxytocin release

Cited by 85 publications

References 10 publications

Relaxin binding in the rat heart atrium.

Relaxin binding in the rat heart atrium.

The Emerging Concept of Relaxn as a Centrally Actng Peptide Hormone with Hemodynamic Actions

Relaxin on induction of parturition in cattle: effects on hormonal, pelvic and cervical changes, and postpartum fertility

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