Uterine growth-promoting effects of relaxin: a morphometric and histological analysis

Abstract

The hormone relaxin has been implicated in the regulation of several processes in the reproductive tract during pregnancy and parturition. This study investigated the uterine effects of relaxin in immature and mature ovariectomized, estrogen-primed rats using morphometric and histochemical analysis. Rats were sprayed at 30 or 70 days of age and given estrogen (5 micrograms) 7 days later. After a week, they received an injection of porcine relaxin (100 micrograms) and were killed 6 h later; controls received vehicle alone. Histological sections were obtained from 7 levels of each uterine horn, and the volumes of endometrium and myometrium were calculated by use of a Zeiss Videoplan Computer Image Analyzer. In immature animals, relaxin treatment doubled uterine weights during the treatment period, and cross sections from relaxin-treated animals exhibited significant increases in the areas of both the myometrium and endometrium, 150% and 130% respectively. Mature animals were less responsive to relaxin although they also exhibited significant increases in uterine weight (31%), myometrial volume (29%), and endometrial volume (22%). With the use of Masson's Trichrome stain for collagen, we observed that relaxin alters the connective tissue framework of both endometrium and myometrium; control uterine collagen appears highly organized and dense with compact collagen fibers, whereas the collagen of relaxin-treated uteri is loosely arranged and disorganized with widely separated collagen fibers. Relaxin-stimulated uteri exhibited significantly greater vascularization, as evidenced by the size of arteries and veins in the vascular region between the circular and longitudinal muscle layers. Increased vascularization and uterine blood flow may be one mechanism involved in relaxin's uterotropic effect and is being investigated further.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of relaxin on mast cells. In vitro and in vivo studies in rats and guinea pigs.

“…Abbreviations used in this paper: [Ca2"]i, intracellular Ca2" concentration; D-Arg, D-arginine; D-NAME, Nw-D-arginine methylester; L-Arg, L-arginine; L-NAME, Nw-L-arginine methylester; MC, mast cell; MeArg, Nw monomethyl-L-arginine; Quin-2 AM, Quin-2 acetoxymethylester; RLX, relaxin. our laboratory on the mammary gland, mesenteric vessels, and pigeon crop sac (4)(5)(6), as well as studies of other authors on the rat uterus (7), RLX was shown to cause striking enlargement of microvessels. Interestingly, our findings on the mammary gland of mice given RLX systemically (8) revealed that vasodilation was not accompanied by a concurrent release of granules from mast cells (MCs), thus suggesting that the action of RLX is independent of the release of vasoactive mediators contained in the MC granules, such as histamine.…”

The vasorelaxant hormone relaxin induces changes in liver sinusoid microcirculation: a morphologic study in the rat

“…In previous studies, RLX has been shown to have powerful vasodilatory action in both sexes (Bigazzi et al 1986, Vasilenko et al 1986, Masini et al 1997, Danielson et al 1999. Therefore, in the current study, we used male rats to exclude any possible influence of endogenous RLX and ovarian steroids on the experimental results, as may have occurred if using cycling female rats.…”

“…These cells are sensitive to substances known to decrease or increase sinusoidal blood flow, such as ethanol (Hijioka et al 1991) and bile acids (Pak & Lee 1993) respectively, as well as to the vasorelaxant hormone relaxin (RLX). RLX is a peptide hormone typical of pregnancy (reviewed by Bani 1997) which has been shown to cause striking vasodilation in several organs (Vasilenko et al 1986, Masini et al 1997, Danielson et al 1999. Among these organs, there are the mesenteric microvessels (Bigazzi et al 1986), which are thought to play an important role in the regulation of portal blood flow and hence, indirectly, in liver perfusion (Rappaport 1973).…”

International Union of Basic and Clinical Pharmacology. XCV. Recent Advances in the Understanding of the Pharmacology and Biological Roles of Relaxin Family Peptide Receptors 1–4, the Receptors for Relaxin Family Peptides

“…Vasodilation in arterioles, capillaries, and venules is a common response to relaxin in reproductive tissues (Vasilenko et al, 1986;Bani et al, 1988;Lee et al, 1992), heart (Bani-Sacchi et al, 1995;Masini et al, 1997;Bani et al, 1998b), liver (Bani et al, 2001), and cecum (Bigazzi et al, 1986). Relaxin is a potent vasodilator in arteries (Conrad, 2010;McGuane et al, 2011b), although the effect is vessel specific (McGuane et al, 2011b).…”