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Title:Relaxin: Target Tissues and Effects on Uterine Contraction in Vivo and in Vitro in the Rat
Author(s):Cheah, Swee Hung
Department / Program:Physiology and Biophysics
Degree Granting Institution:University of Illinois at Urbana-Champaign
Subject(s):Biology, Animal Physiology
Abstract:Possible target tissues for relaxin in estrogen-primed ovariectomized rats were identified by determing (1) the tissue distribution of injected ('125)I-labeled relaxin (('125)I-relaxin) in vivo and (2) the changes in cyclic AMP (cAMP) levels in several tissues following incubation with relaxin in vitro. Porcine relaxin was radioiodinated with ('125)I-labeled Bolton-Hunter reagent. Relaxin retained its biological activity following modification with unlabeled Bolton-Hunter reagent (N-succinimidyl 3-(4-hydroxyphenyl) propionate). Of the tissues examined, thyroid, kidney, liver, spleen, lung and uterus (horns and cervix) had higher concentrations of radioactivity than blood during the first 4 h following the injection of 5 (mu)Ci (approximately 16 ng) of ('125)I-labeled relaxin. Only with the uterus could the higher levels of radioactivity be significantly displaced by the simultaneous administration of 15,000 ng of unlabeled relaxin (P < 0.05). Samples of uterine horns and cervix, liver, kidney, spleen, adrenal, diaphragm, lung, ileum, bladder, ureter and arterial vascular wall were incubated with Krebs-Ringer bicarbonate buffer (pH 7.4, 37C, gas phase 95%O(,2)-5%CO(,2), containing 5.5 mM glucose and 5 mM theophylline). After 15 min of incubation with 4 (mu)g/ml porcine relaxin, only the uterine horns and cervix showed significant increases in cAMP levels over controls (P < 0.001) as measured by radioimmunoassay. The increases in cAMP levels within the uterine horns were time and hormone-dose dependent. It appears that the uterine horns and cervix are target tissues for relaxin in the estrogen-primed ovariectomized rat. Relaxin may exert its biological effects, at least in part, through cAMP.
The effects of relaxin on uterine contractions were investigated in vivo in conscious unrestrained ovariectomized rats treated with various steroids. It was found that spontaneous uterine activity was significantly lower in the estrogen-dominated (0.5 (mu)g estradiol benzoate/day, injected sc) than in the progesterone-dominated (5 mg progesterone plus 0.5 (mu)g estradiol benzoate/day, injected sc) animal. The ovariectomized steroid-untreated rat also demonstrated significantly greater spontaneous activity than the estrogen-dominated animal. Relaxin reduced the spontaneous contractions in the estrogen-dominated and steroid-untreated rats. Additionally, relaxin reduced the oxytocin-and PGF(,2(alpha))-driven uterine contractions in the estrogen-dominated rat. Relaxin also reduced the spontaneous activity in the progesterone-dominated animal, but its effects appeared to be more complex. It was postulated that long term relaxin inhibition of uterine activity in the progesterone-dominated rat involved a biosynthetic step, while the inhibition in the estrogen-dominated and steroid-untreated rats was an acute one, and did not involve an intervening biosynthetic step.
A modified tube electrode for the simultaneous measurement of electrical and contractile activity of the rat uterus in vitro was also described. Preliminary studies using uteri taken from estrogen-primed (2 x 10 ug estradiol benzoate, injected intramuscularly) rats demonstrated its usefulness. The estrogen-dominated uterus in vitro showed significantly more contractile activity than in vivo (P < 0.001), and so some caution must be exercised when extrapolating the in vitro data to the in vivo situation. The electrical activity of the uterus in vitro was found to initiate from the cervical or ovarian end of the horn, conducted throughout the horn, and correlated well with the contractile activity. Relaxin inhibited the spontaneous electrical and contractile activity of the isolated estrogen-primed uterus. It was postulated that relaxin may act in vitro by inhibiting the spiking activity of the pacemaker cells, and also the conduction of action potentials throughout the uterus.
Issue Date:1981
Description:262 p.
Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 1981.
Other Identifier(s):(UMI)AAI8114399
Date Available in IDEALS:2014-12-14
Date Deposited:1981

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