Relaxin, a product of the pregnancy corpus luteum, is a peptide hormone which causes alterations of connective tissue. We have demonstrated an association between maternal serum relaxin concentrations and premature delivery. Our working hypothesis is that relaxin has a physiological role in cervical changes during pregnancy. Hyperrelaxinemia, by accentuating these changes increases the likelihood of premature birth. We propose to study two models of the human cervix. The first is the monkey cervix. The cervix of the monkey is similar to that of the human as is the endocrinology of the monkey luteal phase and early pregnancy. We plan to stimulate the endocrinology of early pregnancy in the rhesus monkey to determine the effects of relaxin on the uterus. Ovariectomized, steroid-replaced rhesus monkeys will be treated with either relaxin vehicle to determine the specific anatomic, microstructural and enzymatic changes causes by relaxin. Our second model is human lower uterine segment (LUS) cells in vitro. We have already shown that these cells contain relaxin receptors and respond to relaxin by increasing expression of proMMP-1 and proMMP-3 and decreasing levels of TIMP-1, changes which promote collagenolysis. We will expand these studies, utilizing clues derived from the in vivo monkey studies. We will compare these results to results obtained from LUS cells of women without corporalutea, who are laxinemic, to observe potential relaxin effects in late pregnancy. We plan to define the mechanisms of action of relaxin on monkey cervical fibroblasts and human lower uterine segment fibroblasts. We will define the interrelationships of relaxin with estrogen, progesterone and other uterotropic substances in these two models. The major clinical problem in obstetrics today is premature birth. There is at present little understanding of the factors which control uterine and cervical function to initiate normal or premature birth. What is clear is that this is a multi-factorial system of overlapping control mechanisms. Relaxin has clearly been shown to be a factor in the process. That relaxin is the only hormone whose levels are associated with prematurity suggests a major role. It is likely that better understanding of the physiological role of relaxin will allow for the development of agents which can better control cervical connective tissue changes to both decrease premature delivery and facilitate delivery at term.
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