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Date of Award

3-1985

Degree Type

Thesis

Degree Name

Doctor of Philosophy (PhD)

Department

Medical Sciences

Supervisor

Professor Robert E. Garfield

Abstract

The muscle of the pregnant uterus transforms into an active and reactive tissue at term which is necessary for expulsion of the fetus and termination of pregnancy. Gap junctions develop between the smooth muscle cells of the uterus immediately prior to term and disappear after delivery. Gap junctions may be providing the structural basis for improved communication between myometrial cells during labor thereby leading to the synchronized coordinated muscle activity required for effective labor. Although gap junctions appear to have significant implications in the termination of pregnancy, the regulation of their presence in the myometrium is not completely understood but may depend upon hormonal changes that occur prior to parturition.

In the studies reported in this thesis, quantitative thin section electron microscopy showed that high doses of estradiol stimulated, whereas progesterone when administered with estradiol, suppressed the presence of myometrial gap junctions in non-pregnant animals. The steroid hormones regulate the presence of gap junctions by controlling the synthesis of the junction proteins probably through their receptor mechanism. In addition, high doses of estradiol may selectively stimulate the synthesis of a prostaglandin which may be required for the development of gap junctions. Prostaglandins appear to be involved in junction regulation since inhibitors of cyclo-oxygenase potentiated estradiol stimulation of gap junctions. Moreover, treatment of pregnant animals with estradiol resulted in the presence of numerous myometrial gap junctions and abortion. These results demonstrate that the steroid hormones and prostaglandins regulate the presence of myometrial gap junctions and that their presence in the myometrium may be a requirement for the occurrence of term as well as preterm labor.

Cell-to-cell communication via gap junctions is also believed to be involved in the control of cellular and tissue growth. The myometrium grows dramatically throughout pregnancy to accommodate the growing fetus. Moreover, the steroid hormones, in particular estradiol, stimulates growth of the uterus and prostaglandins also appear to be involved in the process. Since the hormones and prostaglandins regulate uterine growth and the presence of myometrial gap junctions (see above), the relationship between the two events was further evaluated in this thesis. Studies on non-pregnant animals after various hormonal treatments and in untreated pregnant animals demonstrated that regulation of uterine growth (of which the myometrium is a major component) and the presence of gap junctions in the myometrium are dependent upon the hormonal environment. The results suggest a complex interaction between the steroid hormones, a product of the cyclo-oxygenase and/or lipoxygenase pathway for control of gap junctions and myometrial growth. Myometrial growth may occur because of the lack of gap junctions but the cessation of growth of this tissue does not depend on the presence of the junctions. The development and presence of gap junctions, however, may be partially dependent upon myometrial growth.

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