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Biomedical subjects

M L Casey

Publications and source records attributed to M L Casey.

At least 109 records · Page 6Linked to original sources
PubMed1983

Extra-adrenal deoxycorticosterone production in hypoestrogenic pregnancies: Serum concentrations of progesterone and deoxycorticosterone in anencephalic fetuses and in women pregnant with an anencephalic fetus.

In a continuing effort to define the origin of and the regulation of the production of deoxycorticosterone, we measured deoxycorticosterone and progesterone in the umbilical cord plasma of 16 anencephalic fetuses and newborn infants (21 to 45 weeks' gestation) and deoxycorticosterone, progesterone, 17 beta-estradiol, and estriol in the plasma of 18 women pregnant (16 to 45 weeks) with an anencephalic fetus. Whereas umbilical cord plasma levels of progesterone in the anencephalic fetuses were similar to those of normal abortuses and newborn infants, those of deoxycorticosterone (1.3 +/- 0.21 ng/ml, mean +/- SE) were significantly lower (P less than 0.001) than those in normal abortuses and newborn infants delivered between 31 and 42 weeks' gestation (3.94 +/- 0.26 ng/ml). We found that plasma levels of deoxycorticosterone were significantly correlated (P less than 0.001) to those of progesterone in women pregnant with an anencephalic fetus, as well as in women pregnant with a normal fetus. Plasma levels of deoxycorticosterone (range = 0.14 to 0.92 ng/ml) in women pregnant with an anencephalic fetus were significantly lower than those in women pregnant with a normal fetus; plasma levels of progesterone were similar in both groups. The plasma levels of 17 beta-estradiol and of estriol were extremely low in women pregnant with an anencephalic fetus compared with those in women with a normal fetus and did not vary as a function of gestational age. In one subject who was pregnant with an anencephalic fetus, we found that estrogen treatment (100 mg of diethylstilbestrol/day) for 6 days caused a progressive increase in the serum levels of deoxycorticosterone and in the ratio of the concentration of concentration of deoxycorticosterone to that of progesterone in serum. Both the serum levels of deoxycorticosterone and the ratio of the concentration of deoxycorticosterone and in the ratio of the concentration of deoxycorticosterone to that of progesterone declined after cessation of estrogen treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenal Glands↗
PubMed1983

Stimulation of prostaglandin E2 production in amnion cells in culture by a substance(s) in human fetal and adult urine.

A protein or protein-associated substance(s) in human fetal urine effects a 10- to 600-fold increase in prostaglandin E2 (PGE2) synthesis by human amnion cells maintained in monolayer culture; the increase in PGE2 synthesis is maximal by 12 h. Fetal urine did not cause a similar increase in PGE2 synthesis is maximal by 12 h. Fetal urine did not cause a similar increase in PGE2 synthesis in cells derived from other human tissues tested. A similar PGE2 synthesis-stimulatory activity is present in adult urine and the activity in adult urine is correlated inversely (p less than 0.001) with creatinine concentration. These findings are suggestive that a substance produced in, or excreted by, kidney acts to induce PGE2 synthesis in a tissue-specific manner.

Amnion↗
PubMed1983

Metabolism of arachidonic acid and prostanoids in human endometrial stromal cells in monolayer culture.

In the present investigation, we compared the metabolism of arachidonic acid in human endometrial stromal cells maintained in monolayer culture with that in human decidual tissues. By gas-chromatographic analysis, the distribution of arachidonic acid in glycerophospholipids and in the neutral lipids of decidual tissues and stromal cells in culture was similar. After the addition of [14C]arachidonic acid to the culture medium, steady-state conditions with respect to radioactive labeling of the lipids of the cells were attained after 24 h, except for phosphatidylethanolamine and neutral lipids. The percentage distribution of [14C]arachidonic acid in the lipids of the cells in culture was as follows: phosphatidylcholine, 41%; phosphatidylserine, 5%; phosphatidylinositol, 19%; phosphatidylethanolamine, 22%; neutral lipids, 11%. This distribution of arachidonic acid among the lipids is similar to that in decidual tissue, except for that in phosphatidylethanolamine. The amount of radioactivity in phosphatidylethanolamine continued to increase up to 72 h whereas that in neutral lipids declined after a maximum amount was present at 4 h. In the cells in monolayer culture, [14C]prostaglandin E2 and [14C]prostaglandin F2 alpha were produced from [14C]arachidonic acid, as is true in superfused decidual tissue. The similarities in arachidonic acid metabolism in these cells to that in decidual tissue are supportive of the proposition that endometrial stromal cells in monolayer culture are an appropriate model for the study of the regulation of arachidonic acid release and prostaglandin formation by endometrium and decidua vera.

Arachidonic Acid↗
PubMed1983

Stimulation of prostaglandin biosynthesis by urine of the human fetus may serve as a trigger for parturition.

Urine of the human fetus stimulated prostaglandin biosynthesis in vitro by increasing the conversion of arachidonic acid into prostaglandins. The stimulatory activity in urine from fetuses delivered at term after labor of spontaneous onset was greater than that in urine from fetuses delivered by cesarean section at term before the onset of labor. Such stimulation of prostaglandin biosynthesis by the fetal membranes, by way of a substance released into the urine and thence into amniotic fluid, could serve as a signal for the initiation of parturition.

Adult↗
PubMed1983

Concentrations of deoxycorticosterone, deoxycorticosterone sulfate, and progesterone in maternal venous serum and umbilical arterial and venous sera.

The present investigation was conducted to evaluate the potential for the transfer of deoxycorticosterone (DOC) and deoxycorticosterone sulfate (DOC-SO4) from the fetal to the maternal compartment in near-term human pregnancy. To do so we measured progesterone, DOC, and DOC-SO4 in maternal venous serum and in umbilical arterial and venous sera. The levels of DOC and DOC-SO4 in maternal serum were significantly correlated to each other and to those of progesterone in maternal serum. However, there was no correlation between the levels of DOC or DOC-SO4 in umbilical arterial or venous sera and those of these steroids in maternal serum. Although there was no difference in the concentrations of DOC in umbilical arterial or venous serum, there was a highly significant difference in the umbilical arterial and venous concentrations of DOC-SO4. We conclude that the potential exists for DOC-SO4 from umbilical arterial plasma to enter trophoblasts where it could be hydrolyzed to DOC. The DOC so formed could then be redistributed primarily to the maternal but also to the fetal compartment.

Adolescent↗
PubMed1983

Characterization of catechol-O-methyltransferase activity in human uterine decidua vera tissue.

In the present investigation, we characterized the activity of catechol-O-methyltransferase (COMT) in homogenates prepared from human decidua vera tissue. The specific activity of COMT in decidua vera is greater than that in liver and myometrium and much greater than that in adipose tissue and erythrocytes. The specific activity of COMT in decidua vera obtained at term was significantly greater (p less than 0.001) than that obtained early in gestation. However, we do not as yet ascribe physiologic significance to this finding since the period of time between delivery of the tissue and assay of the enzyme activity may have varied between the two groups.

Adipose Tissue↗
PubMed1983

Characterization of ornithine decarboxylase activity in human uterine decidua vera.

Ornithine decarboxylase (ODC) catalyzes the rate-limiting step in the biosynthesis of the polyamines putrescine, spermidine, and spermine. In the present study, we characterized the activity of ODC in human uterine decidua vera tissue. We evaluated the activity of the enzyme in decidua vera tissue that was obtained from pregnancies at term before or after the spontaneous onset of labor and in decidua vera tissue that was obtained between 8 and 18 weeks' postconceptional gestational age at the time of elective abortion. Among these tissues, no significant differences in ODC activity were demonstrable.

Carboxy-Lyases↗
PubMed1983

Conversion of progesterone to deoxycorticosterone in the human fetus: steroid 21-hydroxylase activity in fetal tissues.

Steroid 21-hydroxylase activity was assayed in microsome-enriched fractions prepared from homogenates of a number of human fetal tissues. The activity of this enzyme was demonstrable in several tissues in addition to the adrenal, kidney, and gonads. The highest specific activities of the enzyme were found in adrenal, skin, kidney and urinary bladder. In addition, 21-hydroxylation of progesterone was demonstrated in microsome-enriched preparations of pancreas, thymus, spleen, testis and ovary. Thus a number of fetal tissues may contribute to the formation of deoxycorticosterone, which is present in high concentrations in plasma of the human fetus compared with those in men and nonpregnant women. Moreover, the potential for the in situ formation of DOC in presumed tissue sites of mineralocorticosteroid action was demonstrated.

Adrenal Glands↗
PubMed1983

Steroid 21-sulfatase activity in human placenta.

Intravenously administered [3H]-deoxycorticosterone sulfate is not metabolized by way of deoxycorticosterone in men or non-pregnant women. Thus, it can be implied that steroid 21-sulfatase is not active in human tissues. On the other hand, evidence has accrued that deoxycorticosterone sulfate is hydrolyzed in human placenta. In the present investigation, we sought to ascertain if steroid 21-sulfatase activity were present in placenta and, if so, to characterize the enzyme activity in this tissue. Steroid 21-sulfatase activity was found to be present in microsome-enriched fractions prepared from human placental tissue; conditions of linearity of the reaction with time and protein concentration were established and the apparent KM of the enzyme for deoxycorticosterone sulfate was 100 microM. Thus, deoxycorticosterone sulfate, which is present in high concentration in plasma of the human fetus, may enter trophoblast wherein it could be hydrolyzed; the deoxycorticosterone formed could be secreted into the maternal circulation. Such a process, together with deoxycorticosterone formation from plasma progesterone in extraadrenal sites, could account for the high concentrations of deoxycorticosterone that are present in plasma of near-term pregnant women.

Dehydroepiandrosterone↗
PubMed1983

Conversion of progesterone to deoxycorticosterone in guinea pig spleen: an animal model for the study of steroid 21-hydroxylase activity in extra adrenal sites.

Steroid 21-hydroxylase activity has been demonstrated, previously, in microsome-enriched fractions prepared from a number of human fetal tissues. The finding that this enzyme activity was present in thymus and spleen is suggestive of the possibility that deoxycorticosterone is important in regulation of immunological processes. In the present investigation, we characterized steroid 21-hydroxylase activity in microsome-enriched preparations of guinea pig spleen. The activity of the enzyme was linear with time for 40 min and with protein concentrations up to 4.8 mg X ml-1 incubation mixture. The apparent Km of the enzyme for progesterone was 0.405 microM. Thus, the potential exists for the biosynthesis of DOC from progesterone in the spleen of the guinea pig as well as in the spleen of the human fetus. Therefore, the guinea pig may be an appropriate animal model for the study of the regulation of steroid 21-hydroxylase activity in the spleen as well as a model for the study of the role of this enzyme in immunologic processes.

Animals↗
PubMed1983

Metabolic clearance rate of plasma deoxycorticosterone sulfate in men and women.

In the present investigation, we determined the metabolic clearance rate of plasma deoxycorticosterone sulfate in adult men and nonpregnant women and in one women pregnant at 42 weeks gestation with an anencephalic fetus. The values obtained varied from 618 to 10701/24 h. The metabolic clearance rate of deoxycorticosterone sulfate, expressed as a function of body surface area, was 495 +/- 31.71/24 h/m2 (mean +/- SEM) and was not significantly different among men and nonpregnant women. In a woman pregnant with an anencephalic fetus at 42 weeks gestation, the metabolic clearance rate of deoxycorticosterone sulfate was 6441/24 h/m2. We suggest that the high clearance rate of this steroid 21-sulfate, compared with those of other steroid sulfates, is due to rapid excretion of deoxycorticosterone sulfate into bile and irreversible metabolism in intestine by bacterial enzymes.

Anencephaly↗
PubMed1983

Sulfurylation of deoxycorticosterone in human fetal tissues.

We determined the specific activity of 21-hydroxysteroid sulfotransferase in a number of human fetal tissues and in tissues of a prepubertal boy (5 years of age). In fetal tissues, the highest specific activities of this enzyme were found in adrenal gland, liver, kidney, intestine, aorta, and testis. In the tissues of the prepubertal boy, 21-hydroxysteroid sulfotransferase activity was demonstrable only in adrenal and liver. Thus, 21-hydroxysteroid sulfotransferase activity is present in some fetal tissues in which DOC may be formed by 21-hydroxylation of progesterone, as steroid 21-hydroxylase activity has been demonstrated previously in adrenal, kidney, and testis. We speculate that sulfurylation of DOC in some tissue sites of DOC formation and action may regulate the action of this mineralocorticosteroid.

Adrenal Glands↗
PubMed1983

Catechol-O-methyltransferase activity in erythrocytes of persons with severe thermal injury.

In the present investigation, we found that the catechol-O-methyltransferase activity (COMT) in erythrocytes of persons with severe thermal injury was strikingly increased when compared with that in erythrocytes of noninjured individuals. The specific activity of COMT in erythrocytes of burned patients was not correlated with extent of burn. Thus the echinocytes of burned persons are another example of abnormal red cells in which COMT activity is increased. This appears to be the first example of increased COMT activity in abnormal erythrocytes that is not associated with large numbers of reticulocytes.

Adult↗
PubMed1983

Extraadrenal steroid 21-hydroxylase activity in a woman with congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency.

The 21-hydroxylation of plasma progesterone (P) has been demonstrated in pregnant, nonpregnant, and adrenalectomized women and in men. The fractional conversion of plasma progesterone to deoxycorticosterone (DOC), [rho]P-DOC BU, among those subjects was 0.009 +/- 0.001 (mean +/- SEM, n = 32). The [rho]P-DOC BU in a woman with congenital adrenal hyperplasia due to apparent adrenal steroid 21-hydroxylase deficiency was 0.010 when she was taking cortisone acetate, and the [rho]P-DOC BU determined when she was not taking cortisone acetate was 0.012. Moreover, the value computed for the fractional conversion of 17 alpha-hydroxyprogesterone to 11-deoxycortisol in this woman (0.004) was similar to that observed in a woman with normal adrenal function (0.005). Therefore, extraadrenal 21-hydroxylase activity in a woman with nonsalt-losing congenital adrenal hyperplasia due to 21-hydroxylase deficiency was similar to that found in persons with normal adrenal function.

Adrenal Glands↗
PubMed1983

Origin and production rates of deoxycorticosterone and deoxycorticosterone sulfate in men and nonpregnant women.

In the present investigation, we evaluated the origin of deoxycorticosterone sulfate (DOC-SO4) and the production rates of DOC and DOC-SO4 in men and women. Previously, we found that there was little or no interconverion of plasma DOC and DOC-SO4; this finding was reconfirmed in the present investigation. After the iv infusion of [3H]DOC-SO4 and [14C]DOC, urine was collected for 5 days, DOC-SO4 was isolated and purified as unconjugated DOC, and tetrahydro-DOC glucuronoside was isolated and purified as the unconjugated metabolite. The production rate of DOC in these subjects (mean +/- SEM, 66 +/- 9.8 micrograms/24 h) was computed from the specific activity of urinary [14C]tetrahydro-DOC (glucuronoside); the production rate of DOC-SO4 in these subjects (92 +/- 15.9 micrograms/24 h) was computed from the specific activity of urinary [3H]DOC-SO4. The production rates are expressed on the basis of the molecular weight of DOC. Since plasma DOC and DOC-SO4 are not interconverted, we conclude that both steroids are secretory products, presumably from the adrenal cortex.

Adult↗
PubMed1983

Hypercholesterolemia due to elevated low density lipoprotein-cholesterol in newborns with anencephaly and adrenal atrophy.

In the present investigation, we evaluated the relationship between plasma lipoprotein-cholesterol and adrenal steroid production in abortuses and newborns in whom the adrenal was expected to be atrophic, i.e. in anencephalics. We found that umbilical cord plasma levels of dehydroepiandrosterone sulfate (DS) in 23 anencephalics delivered between 13.5 and 45.5 weeks of gestation (mean +/- SE, 176 +/- 37 ng/ml) were significantly lower than those in normal newborns of similar gestational ages; the umbilical cord plasma concentrations of cortisol in many anencephalics, however, were within normal limits. The levels of total cholesterol (134 +/- 10 mg/dl) and low density lipoprotein (LDL)-cholesterol (94 +/- 8 mg/dl) were substantially higher (up to 4-fold) in umbilical cord plasma of anencephalics than in umbilical cord plasma of normal newborns. The mean level of high density lipoprotein-cholesterol in umbilical cord plasma of anencephalic abortuses and newborns (38 +/- 4 mg/dl) was approximately 50% higher than that in normal newborns. The lowest plasma cholesterol level (56 mg/dl) and a concentration of DS (480 ng/ml) that was among the highest seen in the group of anencephalics were found in an anencephalic newborn in whom adrenals were of near-normal weight. Plasma cholesterol levels were inversely correlated to adrenal weights and plasma DS levels, and plasma DS levels were correlated to adrenal weight. Whereas the estimated plasma pool of DS in normal newborns increased to over 300 micrograms during the latter part of gestation, that of anencephalic newborns was much lower (less than 1 to 26 micrograms) and did not appear to increase as a function of gestational age. Conversely, the estimated plasma pool of cholesterol in normal newborns appeared to decline slightly during the last 10 weeks of gestation (80 mg at term), whereas that of anencephalic newborns expanded greatly near term; levels (approximately 200 mg) were attained that were about 3 times those in normal newborns. We conclude that the hypercholesterolemia in anencephalic newborns, due primarily to extremely elevated plasma levels of LDL-cholesterol, is a result of decreased uptake and utilization of plasma LDL-cholesterol for steroid biosynthesis by the adrenals. Since hypercholesterolemia is apparently early in gestation in anencephalic abortuses, we speculate that in normally developing fetuses, plasma LDL-cholesterol is used as substrate for adrenal steroidogenesis early in gestation as well as near term when the rates of growth and steroid production by the adrenals accelerate markedly.

Adrenal Glands↗