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Progesterone is known to prevent labour at term in domestic animals, but its effect in primates is uncertain. 5 alpha-reduced progesterone metabolites are more potent central nervous system depressants than progesterone is itself. Progesterone and its 5 alpha-reduced metabolites also relax pregnant rat myometrium in vitro. The serum concentration of the initial 5 alpha-reduced metabolite, 5 alpha-pregnane-3,20-dione, is high during pregnancy, but decreases significantly prior to parturition. The next metabolite, 5 alpha-pregnane-3 alpha-ol-20-one, has anaesthetic properties in human beings. The purpose of this study was to ascertain whether these progesterone metabolites also suppress contracting human uterine muscle at term. An in vitro model was devised. Strips of human myometrial muscle were mounted in organ chambers and after regular contractions had become established, the strips were superfused with progestin solutions. The progestins were dissolved in the buffer using an ultrasound bath. Progesterone, used as reference substance, slightly reduced the measured amount of muscular work performed per contraction, recordable after 18 min of exposure (p less than 0.05). Similar results have been reported previously in the literature; 5 alpha-pregnane-3 alpha-ol-20-one showed the same tendency though not significant at the 5% level. 5 alpha-pregnane-3,20-dione evidently reduced the contraction frequency after 10 min of exposure (p less than 0.05). None of the substances affected the duration of the contraction. These 5 alpha-reduced progesterone metabolites are thus not potent inhibitors of contracting human term myometrium in vitro.

Some structures in the human myometrium, namely; caveolae, extracellular space and gap junctions were quantified in tissues from nonpregnant women, women who were not in labor, and women in spontaneous labor or oxytocin-induced labor, in order to reveal morphologic differences that would contribute to explaining the events leading to labor. Transmission electron micrographs taken from tissues from twenty-four pregnant and ten nonpregnant women were studied.Differences were observed in cell growth which was accompanied by enlargement of the extracellular space, and in gap junctions. Gap junctions were demonstrated in nonpregnant women, and even in one postmenopausal woman. Their frequency and size increased gradually between groups of pregnant women in the order of non-labor, oxytocin-induced labor and spontaneous labor. The increase in size of the junctions was less than the increase in number.Gap junctions are most frequently found in human myometrial cells in spontaneous labor, which strongly suggests a role for these structures in the termination of pregnancy. The effect of oxytocin on the appearance of gap junctions was negligible; hence, the contribution of oxytocin to establish myometrial contractile synchronicity is thought to be minor. Caveolae are probably not relevant for the initiation of labor as their distribution did not differ between the groups.

Smooth muscle is capable of contracting in response to mechanical distension. Even though the structural basis for this phenomenon is not completely clear, a method has been designed by which the contractile response to mechanical distension of the human uterine muscle can be determined in vivo. The distension is enforced sinusoidally within the frequency range 0.006— 1 Hz, by filling and emptying a rubber balloon introduced into the uterine cavity. A tonometric index of the myometrium is defined using Hook's law after the approximate evaluation of a contratile modulus and the tangential stress and strain in the innermost layer of the uterine wall. The regression lines of tonometric indices upon frequency are determined and intercepts of the equations for basic conditions are compared with those obtained during the administration of pharmacologically active agents. In a pilot study, this system, now modified for the evaluation of drug effects during early pregnancy, has been tested and found reliable.

Smooth muscle is capable of responding by contraction to mechanical distension. Neither the structural basis for this phenomenon nor the theories of smooth muscle behavior are completely clear. A method is now described by which the contractile response to mechanical distension of the human uterine muscle in vivo is determined. The distension is enforced sinusoidally within the frequency range 0.005-2 Hz, by filling and emptying a rubber balloon introduced into the uterine cavity. A tonometric index of the myometrium is defined using Hook's law after the approximate evaluation of a contractile modulus and the tangential stress and strain in the inner layer of the uterine wall. The regression line of indices upon frequency is calculated and intercept and regression coefficient of the equation for basic conditions are compared with those obtained during administration of pharmacologically active agents. It is suggested that the differences in intercepts and regression coefficients be used as a measure of drug effect.

Myometrial lactate dehydrogenase isoenzymes were investigated in 32 pregnant women and in 21 women during labor. During pregnancy and labor the H-type LDH isoenzymes were found to preponderate in contrast to M-type LDH isoenzymes. Both H-LDH and M-LDH isoenzyme activities showed a tendency to increase in normal pregnancy. In severe pre-eclampsia and in chronic hypertension, the uterine M-LDH level decreased. In normal labor, M-LDH activity declined in both the uterine and the rectus abdominis muscles.

Ever since Csapo (1) presented his progesterone block theory the plasma concentration of progesterone and estradiol has been rigorously studied by a series of investigators. Although some experimental evidence in animals supports this hypothesis, the results of studies in man do not (2, 3, 4). On the other hand it is more reasonable to think that the biological activity of the hormones will be governed by the concentrations in the tissue. Recent data from studies in man, rabbit and guinea-pig in this laboratory clearly showed that plasma concentrations of estradiol and progesterone were poorly reflected in the myometrium (see 5 for reference). Another interesting feature that was revealed by this comparative analysis was that during pregnancy the concentration of progesterone in the human myometrium was 50 to 100 times greater than that in the guinea-pig myometrium in spite of similar concentrations in the plasma in the two species (5). These observations led us to read-dress the question of the role of p...

Present knowledge of local blood flow in the human myometrium is based on relatively few observations. Total uterine blood flow has been measured by electromagnetic flowmeter (Assali et al., 1960) and by NzO-technique (Assali et al., 1953; Metcalfe et al., 1955), but no information on local blood flow in the myometrium can be obtained by these methods. A relative measure of local myometrial blood flow may be obtained by heat conductivity (Prill, 1959) or local clearance of Na24 (McCall and Sopp, 1951), but neither method gives an absolute flow measurement. Theoretically, local clearance of Xenon133 injected into the myometrium can be interpreted in terms of absolute flow per gram of tissue, and measurements have been described both for isthmus and cervix in pregnant and non pregnant women (Munck et al., 1964; Lysgaard and LefBvre, 1965). This article presents data on local blood flow in the fibromuscular tissue of the cervix in humans measured by the hydrogen desaturation technique (Aukland et al., 1964). The criteria for acceptable measurements are discussed on the basis of studies on the reproducibility of subsequent measurements in a given area, and on comparison of simultaneous measurements in different areas of the cervix.