Growth-Promoting Effects of Relaxin and Related Compositional Changes in the Uterus, Cervix, and Vagina of the Rat*

Abstract

Although the precise role of relaxin has yet to be elucidated, it has been implicated in the regulation of physiological and biochemical processes in the reproductive tract during pregnancy and parturition. In this study, the growth-promoting effects of relaxin and related compositional changes in the uterus, cervix, and vagina of immature ovariectomized estrogen-primed rats were examined. Relaxin increased the wet weight of the uterus, cervix, and vagina in a significant and linear manner over the log of the dose range (1-30 micrograms; 6 h). The increase in uterine weight was due to increases in both dry weight and water content at all doses. A dose of 1 microgram relaxin induced maximal increases in dry weights in the cervix and vagina over control values; higher doses increased wet weight, but these changes were due solely to increases in water content. Thirty micrograms of relaxin were found to increase total soluble protein and glycogen content of the vagina above control values after 6 h. Relaxin did not alter the total collagen levels of the uterus or cervix, and collagen concentrations were significantly reduced in these organs 6 and 24 h after treatment. Total glycosaminoglycan levels were elevated by relaxin in the uterus (6 h) and cervix (24 h). Total vaginal collagen was increased 24 h after relaxin injection, but the collagen concentration was decreased over the time interval studied, and glycosaminoglycan levels in the vagina were unaltered. In summary, relaxin stimulates growth of the uterus, cervix, and vagina by increasing water content and tissue mass. The increases in distensibility that relaxin induces in these organs appear to be related to changes in the fluid matrix and proteoglycan metabolism rather than alterations in collagen concentration, at least 6-24 h after a single injection. These results support the hypothesis that relaxin plays a significant role in the maintenance of pregnancy through its contribution to fetal accommodation and in the facilitation of parturition through expansion of the entire birth canal.

Differential regulation of insulin-like growth factor binding protein secretion from human decidual cells by IGF-I, insulin, and relaxin.

“…Alternatively, decidual IGF-BP has been shown to inhibit 1251I-IGF-I binding to both placental and endometrial receptors (46 The effects of relaxin on IGF-BP-I secretion have not been previously described. Extraluteal localization of relaxin to human endometrial stromal cells and decidual cells has been noted (49)(50)(51)(52), and the uterus is a major target tissue for relaxin effects on tissue growth and myometrial contractility (53)(54)(55)(56). The present observations suggest that relaxin may also be involved in the regulation of IGF-BP secretion by uterine tissues through autocrine or paracrine mechanisms.…”

Uterotrophic effects of relaxin related to age and estrogen receptor activation in neonatal pigs

“…Uterotrophic actions of relaxin, first described in the rat (Steinetz et al 1957), include both uterine water imbibition (Steinetz et al 1957, Zarrow & Brennan 1957 and increased uterine dry matter content associated with protein, collagen and glycogen accretion (Steinetz et al 1957, Vasilenko et al 1980, 1981, Vasilenko & Mead 1987. Early studies indicating that relaxin-rich extracts promoted endometrial growth in juvenile and ovariectomized rhesus monkeys (Hisaw & Hisaw 1964, Dallenbach-Hellweg & Hisaw 1966 were later confirmed by work involving the purified hormone (Goldsmith et al 2004), which showed that relaxin also stimulated endometrial angiogenesis.…”

“…However, it is clear that some of these effects mimic those induced by estrogen. For example, like estradiol, relaxin increased expression of uterine insulin-like growth factor-I (Ohleth et al 1997, Kowalski et al 2004, gap junctions (Risek et al 1995, Lenhart et al 1999, vascular endothelial growth factor (Cullinan-Bove & Koos 1993, Unemori et al 1999, and uterine vascularization (Vasilenko & Mead 1987, Cullinan-Bove & Koos 1993. Estrogen receptors, which function classically as hormoneregulated transcription factors, can be activated both directly by estrogen and indirectly via crosstalk with peptide growth factor signaling pathways (Ignar-Trowbridge et al 1992, Ma et al 1994, Smith 1998.…”

Administration of pig relaxin to beef heifers 4 or 7 days pre partum

“…Relaxin is involved in cervical dilatation (Downing & Sherwood, 1985), relaxation of the pubic symphysis (Steinetz et ai, 1960), inhibition of uterine contractility (Porter, 1971), and stimulation of uterine growth (Vasilenko & Mead, 1987). Intracervical administration of pig relaxin to primigravid beef heifers 4 or 5 days before expected parturition induced cervical dilatation and increased pelvic area Musah et ai, 1986a, b).…”