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The relaxin knockout (rlx -/-) mouse was used to assess the effect, during pregnancy, of relaxin with regard to water, collagen content, growth, and morphology of the nipple (N), vagina (V), uterus, cervix (C), pubic symphysis (PS), and mammary gland (MG). The results presented here indicate that during pregnancy, relaxin increases the growth of the N, C, V, and PS. Large increases in water content in the PS (20%) occurred in pregnant (Day 18.5) wild-type (rlx +/+) mice but not in rlx -/- animals. This indicates that in the PS, relaxin might increase the concentration of a water-retaining extracellular matrix component (hyaluronate). In the pregnant rlx +/+ mouse, collagen content decreased significantly in the N and V but not in other tissues. There were no significant changes in the rlx -/- mouse. This contrasts with findings in the rat, in which relaxin has been found to cause decreases in collagen concentrations in the V, C, and PS. Histological analysis showed that the collagen stain was more condensed in the tissues (V, C, PS, N, and MG) of rlx -/- mice than in those of rlx +/+ mice. This phenomenon indicates that the failure of collagen degradation and lack of growth in the N underlie the inability of the rlx -/- mice to feed their young, as reported previously. Vaginal and cervical luminal epithelia, which proliferated markedly in the rlx +/+ pregnant mice, remained relatively atrophic in the rlx -/- mice. As proliferation and differentiation of uterine and vaginal epithelia are thought to be induced by a paracrine stromal factor that acts upon estrogen stimulation, our results indicate that relaxin may be this paracrine factor.

The tensile strength of fetal membranes is largely due to their collagen content. In this study we have examined the changes in collagen in the amniotic and allantoic membranes of the sheep over a wide gestational range (27-142 days of gestation; term, 145-150 days). The results have been correlated with volume changes in normal development, and in particular, the changes in allantois have been studied after a rapid and extensive increase in allantoic volume, as a result of maternal dexamethasone treatment (0.76 mg h-1 for 48 h) from Day 60 of gestation. Electron microscopy and immunohistochemistry were used to delineate collagen distribution, and gel electrophoresis was used to assess the relative proportions of each type. In the amnion, collagen content increased from 37 +/- 4% to 50 +/- 1% dry weight of the tissue from 41-102 days and declined slightly thereafter. In the allantois, collagen content increased from 20 +/- 1% at Day 27 to 50 +/- 6% at Day 142, significantly correlated with a volume increase from 25 +/- 3 mL to 813 +/- 274 mL. Collagen types I (>85%), III (10%) and small amounts of types IV and V (<5%) were identified in both membranes at all ages. When allantoic fluid volume was increased rapidly by maternal dexamethasone infusion, there was a significant decrease in collagen content from 38 +/- 6% to 25 +/- 2% (P < 0.05). By immunohistochemistry it was observed that both epithelial cells and fibroblasts were synthesizing collagen.

The aim of this study was to examine the effects of relaxin on collagen content, solubility, and composition in the rat pubic symphysis. Nonpregnant, female Sprague-Dawley rats were bilaterally ovariectomized and either unprimed or primed with estrogen or progesterone alone, or a combination of estrogen and progesterone. One week later these animals were given increasing doses of a synthetic human (gene-2) relaxin (0-100 micrograms) before being killed 16 h later. Their pubic symphysial tissues were then removed and analyzed for collagen content and solubility, whereas collagen composition was determined by SDS-PAGE. Relaxin administration significantly increased the length (140 +/- 6%) and weight (170 +/- 9%) of the interpubic fibrocartilage in estrogen-primed rats (n = 15). At the same time, it decreased the total collagen content by 68 +/- 6%, without altering the proportions of collagen types, which were predominantly type I (85%) and type II collagen (15%). Relaxin administered alone reduced the total collagen content by 64 +/- 4% but had no effect on collagen solubility or composition. Progesterone abolished the effects of relaxin in estrogen-primed rats. It is concluded that relaxin has a potent effect on the amount of collagen in the rat pubic symphysis that is enhanced by estrogen and antagonized by progesterone. The changes in the extracellular matrix within the pubic symphysis induced by relaxin may be important in the modifications that this tissue undergoes during pregnancy.

The gastric ulcerogenic effect of the glucocorticoid, prednisolone, was studied in albino rats. Shay operation in forestomachectomized rats with intact adrenals induced acute gastric ulcers in the corpus, whereas adrenalectomy prevented the development of gastric ulcers in another group of forestomachectomized Shay rats. Only superficial erosion of gastric epithelium was noticed in 66.67% of these rats. Administration of prednisolone to another group of similarly operated rats increased the number and severity of gastric ulceration, whether the adrenals were ablated or otherwise. From the observation of acid and mucous content of the stomach, it is postulated that the reduced mucous secretion may be an important predisposing factor in gastric ulcerogenic effect of steroids.