Estrogen use and endometrial cancer.
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Estrogens↗
Biomedical subjects
J E Buster
Publications and source records attributed to J E Buster.
Adrenocorticotropin and glucocorticoid concentrations in fetal and maternal plasma of rabbit does continuously infused with cortisol from day 21 to day 24 of gestation.
Previous studies have suggested that suppression of fetal rabbit adrenocorticotropin (ACTH) secretion results in impaired development of ACTH-specific adenylate cyclase activity. In order to test this hypothesis we measured fetal and maternal plasma ACTH, cortisol, and corticosterone concentrations in control does and does infused with 0.3 mg of cortisol/hour at 21 to 24 days of gestation. This cortisol infusion regimen significantly depressed maternal and fetal plasma ACTH and corticosterone concentrations but did not change fetal serum cortisol concentrations. These findings further support the hypothesis that fetal ACTH plays a role in the normal development of the adenylate cyclase catalytic portion of the ACTH receptor complex and adrenal differentiation during this critical period of fetal life.
Adenylyl Cyclase Inhibitors↗
Comparison of two rapid cortisol radioimmunoassays for use in the fetal sheep.
Cortisol radioimmunoassays (RIA's) utilizing highly specific antisera combined with a simple ethanol protein precipitation procedure (ETOH-PPT) are widely utilized to measure cortisol in human plasma. This same type of RIA has been assumed specific for measurement of cortisol in the plasma of several different species of experimental animals. In order to test this assumption as applied to fetal ovine plasma, we compared an ETOH-PPT cortisol RIA with another rapid cortisol assay which utilizes a dichloromethane extraction (DM-E) step. The DM-E assay in turn was compared with a chromatographic assay previously shown to be highly specific for measurement of fetal plasma cortisol in this species. Fetal ovine plasma cortisol concentrations determined by the DM-E method were nearly identical to the concentrations obtained by the specific chromatographic RIA procedure. On the other hand, the ETOH-PPT RIA grossly overestimated cortisol concentrations when compared with the DM-E RIA. While the rapid DM-E RIA appears to be suitable for use in fetal ovine plasma, the widely used ETOH-PPT RIA yields spuriously high and unpredictable values and must be considered unreliable. These comparisons demonstrate the need for careful reassessment of steroid assays prior to their application in experimental animals even though they have been previously documented as specific in human plasma.
Animals↗
Validation of a specific radioimmunoassay to measure plasma cortisol in the fetal sheep.
A procedure utilizing co-chromatography and complementary antiserum comparisons was employed to assess the specificity of a cortisol radioimmunoassay for use in the chronically catheterized fetal sheep preparation. Complementary antiserum comparisons is a technique by which two different cortisol antisera, prepared from conjugates attached at opposite ends of the cortisol molecule, were used to determine cortisol concentrations in the same ovine fetal plasma specimens. Results were not significantly different between the two groups, each measured by a different antiserum. This procedure may be used to assess assay specificity in any species in which steroid radioimmunoassays are being adapted.
Animals↗
Interrelationships of circulating maternal steroid concentrations in third trimester pregnancies. I. C21 steroids: progesterone, 16 alpha-hydroxyprogesterone, 17 alpha-hydroxyprogesterone, 20 alpha-dihydroprogesterone, delta 5-pregnenolone, delta 5-pregnenolone sulfate, and 17-hydroxy delta 5-pregnenolone.
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17-alpha-Hydroxypregnenolone↗
Interrelationships of circulating maternal steroid concentrations in third trimester pregnancies. II. C18 and C19 steroids: estradiol, estriol, dehydroepiandrosterone, dehydroepiandrosterone sulfate, delta 5-androstenediol, delta 4-androstenedione, testosterone, and dihydrotestosterone.
This report describes aggregate time trend effects of advancing gestational age on circulating maternal concentrations of 17beta-estradiol (E2), estriol (E3), dehydroepiandrosterone (D), dehydroepiandrosterone sulfate (D-S), delta 5-androstenediol (delta 5 diol), delta 4-androstenedione (delta 4 A), testosterone (T), and dihydrotestosterone (DHT) in a sequential series of 155 blood samples obtained from 19 normal pregnant women ranging from 26-40 weeks gestational age. Only E2, E3, and D-S show aggregate time trend effects. Log (E2) plots as a linear positive sloping curve from 26-40 weeks. Log (E3) plots as a positive sloping curve that is significantly steeper than log (E2) (P less than 0.05). Log (D-S) plots into a negative sloping curve which mirrors the pattern for log (E2) but cannot be statistically associated with log (E2) except for the opposite sign of their slopes, which are both significantly different from a zero slope (P less than 0.05). delta 4 A, T, DHT, delta 5 diol, and D show no aggregate time trends; however wide, comoving undulations for delta 4 A, T, DHT, and delta 5 diol between 26-28 and 38-40 weeks are confirmed in time by comparison of log mean plots and in magnitude by regressing the C19 steroids on one another. D shows virtually no association with the other C19 steroids. All C19 steroids, except for T, circulate at nonpregnant concentrations, implying that there is little placental secretion of these steroids into the maternal circulation.
Androgens↗
Interrelationships of circulating maternal steroid concentrations in third trimester pregnancies. III. Effect of intravenous cortisol infusion on maternal concentrations of estriol, 16 alpha-hydroxyprogesterone, 17 alpha-hydroxyprogesterone, progesterone, 20 alpha-dihydroprogesterone, delta 5-pregnenolone, delta5-pregnenolone sulfate, dehydroepiandrosterone sulfate, and cortisol.
The effect of a large dose (1000 mg) of iv cortisol-hemisuccinate on circulating steroid concentrations in five women, 28--34 weeks, gestational age, is reported. Maternal concentrations of estriol, 16 alpha-hydroxyprogesterone, 17 alpha-hydroxyprogesterone, progesterone, 20 alpha-dihydroprogesterone, delta 5-pregnenolone, delta 5-pregnenolone sulfate, dehydroepiandrosterone sulfate, and cortisol were measured by RIA before and at 8 and 12 h after iv cortisol infusions at 0 and 8 h. Data were evaluated by repeated measure analysis of variance. Estriol and 17 alpha-hydroxyprogesterone suppressed initially (P less than 0.05) and suppressed further with retreatment and increased treatment time (P less than 0.05). Dehydroepiandrosterone sulfate and progesterone suppressed initially (P less than 0.05) but did not suppress further with retreatment and increased treatment time (P greater than 0.05). delta 5-Pregnenolone and delta5-pregnenolone sulfate increased initially (P less than 0.05) but did not increase further (P greater than 0.05). Concentrations of 16 alpha-hydroxyprogesterone and 20 alpha-dihydroprogesterone were unchanged by cortisol infusion initially (P greater than 0.1) and with retreatment and increased treatment time (P greater than 0.1).
20-alpha-Dihydroprogesterone↗
Subhourly variability of circulating third trimester maternal steroid concentrations as a source of sampling error.
Seven plasma samples from five normal third trimester pregnant women, drawn every 5 and 15 min at similar times on 2 days, 2 days apart, were measured in quadruplicate for estradiol (E2), estriol, progesterone, 16 alpha-hydroxyprogesterone, and 17 alpha-hydroxyprogesterone (17P). The mean of the 22 samples obtained from each subject for each steroid was used as a reference mean. Individual determinations were converted to percentages of the reference mean which was normalized to 0%. All pregnancies were uncomplicated, and all mean values were within the normal range for gestational age. Variability about the reference mean for single samples, however, range from a low of -80% to a high of 150%. The single sample, 95% confidence intervals for individual steroids pooled from the five subjects (110 determinations) range from +/- 36% (E2) to +/- 60% (17P). Mean percentage coefficients of variation between 5-min and 15-min sampling sequences were compared by analysis of variance. There is no significant difference between the mean percentage coefficients of variation of a 5-min as opposed to a 15-min sampling sequence for any of the hormones measured. The 95% confidence interval width around the reference mean is a function of the number of samples obtained. Because the 95% confidence interval width from 110 measurements decreases approximately as 1/ square root n with increasing sampling size, the decrement progressively diminishes. For E2, the least variable steroid, a one-sample 95% confidence interval width of +/- 36% decreases to approximately +/- 18% with four samples or approximately +/- 12% with nine samples. For 17P, the most variable steroid, a one-sample 95% confidence interval width of +/- 60% decreases to approximately +/- 30% with four samples or approximately +/- 20% with nine samples. Multiple sampling with plasma pooling is required for the accurate study of steroid concentrations in individual subjects in late pregnancy.
17-alpha-Hydroxyprogesterone↗
Serum unconjugated estriol levels in the third trimester and their relationship to gestational age. II.
The purpose of this study was to further validate a preliminary report concerning the clinical usefulness of serum unconjugated estriols as a marker of gestational age. Serial estriol values from 50 women with uncertain dates were plotted on semilogarithmic graphs and the gestational age predicted from the timing of the abrupt surge in estriol values which normally occurs between 35 and 36 weeks. The gestational age at birth, as determined by careful neonatal examination, agreed with the age predicted by the estriol surge within +/- 1 week.
Estriol↗
Serum unconjugated estriol levels in the third trimester and their relationship to gestational age.
Maternal unconjugated estriol levels were measured throughout the 28 to 41 week interval in two groups of accurately dated normal pregnancies. The first group consisted of randomly sampled pregnancies on which 285 unconjugated estriol determinations were performed. The logarithms of the mean values plotted into a positive sloping, relatively straight line which was disrupted by a plateau originating at 31 to 32 weeks and terminated at 35 weeks where there began a steep surge to a point at 36 weeks (surge point) that returned values to fit the previously established straight line. To investigate these findings in individual pregnancies, a second group of nine subjects was studied with serial unconjugated estriol determinations. In all nine of these subjects, the surge point could be identified statistically and occurred at a mean gestational age of 36.0 +/- 0.6 (1 S.D.) weeks. Data from the first group of randomly sampled pregnancies indicate that the surge point occurred around a mean gestational age of 36.0 weeks and was confirmed by data from the second group of serially sampled individual subjects showing the surge point as a statistically definable marker in normal pregnancies.
Adrenal Glands↗
A comparison of two glucocorticoid regimens for acceleration of fetal lung maturation in premature labor.
This study compares fetal corticoid response from conventional dose (12.0 mg) intramuscular betamethasone to large dose (1,000 mg) intravenous cortisol administered to women in premature labor for acceleration of fetal lung maturity. To compare these two regimens, 14 women selected at random were treated in groups of seven with either cortisol or betamethasone. Peripheral levels of unconjugated estriol were measured by specific radioimmunoassay prior to the cortisol dose and at 1, 4, 8, and 12 hours following the dose. The rate of corticoid delivery to the fetal hypothalamic-adrenal axis was estimated by the per cent suppression of unconjugated estriol at each post-treatment interval. Least-squares regression lines fitted (P less than 0.01) for each regimen were compared for time saved (delta t) when cortisol was used. Mean delta t (1, 4, 8, and 12 hours) was 9.0 +/- 0.2 S.E.M. hours. It is concluded that: (1) Intravenous cortisol delivers a fetal corticoid effect that is significantly more rapid in onset and more profound in magnitude than does intramuscular betamethasone and that (2) the cortisol regimen is probably better suited to the acceleration of fetal lung maturation in premature labor when time is short and rapid action is essential.
Adolescent↗
Simultaneous comparison of delta 5-3beta-hydroxysteroid levels in the fetoplacental circulation of normal pregnancy in labor and not in labor.
Concentrations of pregnenolone (delta5P), dehydroepiandrosterone (DHEA), 16alpha-hydroxydehydroepiandrosterone (16alpha-OH DHEA), pregnenolone sulfate (delta5P-S), and dehydroepiandrosterone sulfate (DHEA-S) were measured simultaneously by radioimmunoassay in individual, paired umbilical artery (UA) and vein (UV) sera from 18 normal term pregnancies, 6 in labor, 12 not in labor. Mean UA and UV levels +/- SEM (ng/ml) were for delta5P: 30.39 +/- 1.69, 35.55 +/- 3.06; DHEA: 12.31 +/- 2.34, 3.66 +/- 0.38; 16alpha-OH DHEA: 7.48 +/- 0.63, 10.59 +/- 0.78; delta5P-S: 1,652 +/- 154, 1,486 +/- 130; DHEA-S: 2,122 +/- 134, +/- 134, 1,906 +/- 134. Umbilical artery delta5P-S, DHEA-S, and DHEA levels were significantly higher than UV levels, whereas the reverse was true for delta5P and 16alpha-OH DHEA. The inverse arterio-venous (A-V) gradient for 16alpha-OH DHEA was contrary to previous published reports using pooled samples. Comparison by linear regression of paired UA and UV steroid concentrations of delta5P, delta5P-S, DHEA, and DHEA-S revealed a significant correlation (P less than 0.01) for each steroid. Labor was associated with a significant increase in UA levels of DHEA-S and a smaller, but not quite significant, increase in UA levels of delta5P-S, while similar changes for unconjugated delta5-3beta-hydroxysteroids were not observed. Mean A-V gradients between the group of patients in labor and those not in labor were not significantly different. These data demonstrate that: 1) a significant difference between UA and UV concentrations exists for delta5P, DHEA, 16alpha-OH DHEA, delta5P-S, and DHEA-S; 2) there is a significant correlation between UA and UV concentrations for delta5P, DHEA, delta5P-S, and DHEA-S, implying that each fetoplacental unit maintains an equilibrium relative to these steroid concentrations in the umbilical circulation; 3) labor is associated with a significant increase in UA levels of DHEA-S and probably of delta5P-S.
Blood↗
Adenocarcinoma of the endometrium in women taking sequential oral contraceptives.
Abnormal bleeding while taking oral steroidal contraceptives has been managed by changes in pill or addition of estrogen or progestin moieties. Diagnostic procedures, classically indicated, are universally not undertaken or postponed. Three cases of adenocarcinoma of the endometrium in relatively young patients using sequential oral contraceptives for cause are presented to reiterate the need for tissue diagnosis when abnormal bleeding occurs as a common side-effect of contraceptive therapy.
Adenocarcinoma↗
Peripheral and Ovarian Steroids in Ovarian Hyperthecosis.
Serum levels of cortisol (F), pregnenolone (delta5-P), 17-hydroxypregnenolone (17-delta5-P), progesterone (P), 17-hydroxyprogesterone (17-P), androstenedione (A), testosterone (T), 5alphadihydrotestosterone (DHT), dehydroepiandrosterone (DHEA), its sulfate (DHEA-S), estrone (E1), and estradiol-17beta (E2) were measure in 2 virilized patients with ovarian hyperthecosis. Daily morning blood samples were obtained for 6 consecutive days. Dexamethasone (Dex) 2 mg/day was administered orally starting after venipuncture on the second day and continued for 5 days. Human chorionic gonadotropin (hCG) was administered intramuscularly on the afternoon of the fourth and fifth days. Following the suppression-stimulation test, both patients underwent abdominal hysterectomy and bilateral salpingo-oophorectomy. At the time of surgery, samples of peripheral and ovarian vein blood were obtained for steroid measurements. Blood samples were also obtained postsurgery to evaluate the effect of ovariectomy on the steroid levels. Of significance were the following observations: 1)Although both patients were eumenorrheic, no corpus luteum or corpus albicans was seen on histologic examination of the ovaries. 2)Of the androgens measured, only peripheral T and DHT were elevated and did not suppress on Dex treatment, but decreased to low levels following ovariectomy, pointing toward the ovary as the source of excess T and DHT. Both patients had elevated T and DHT in the ovarian vein samples. 3)In 1 patient the ovarian vein samples shoed elevated F levels with a significant ovarian-peripheral venous gradient for this steroid, and indication of ovarian secretion of F in this patient. 4)The levels of 17-P were elevated in both patients, did not suppress on Dex, and increased markedly following hCG, suggesting the ovary as the source of excess 17-P. Since A levels were normal and did not increase concomitantly with 17-P levels following hCG, it is likely that the patients had a decreased activity of the ovarian C17-20 desmolase, the enzyme responsible for the conversion of 17-P to A.
Adrenal Cortex Function Tests↗
Effect of dexamethasone on serum cortisol and androgen levels in hirsute patients.
The serum levels of the following steroids were measured in 59 hirsute patients before (control) and after (post-dexamethasone) administration of dexamethasone (Dex) for 7 days: cortisol (F), dehydroepiandrosterone (DHEA), its sulfate (DHEA-S), androstenedione (A), testosterone (T), and 5alpha-dihydrotestosterone (DHT). Assuming that Dex-suppressibility implied adrenal origin, the source of excess androgens was also evaluated. All patients showed elevated level of only one androgen: 4 had elevated DHEA-S; 4 had elevated T; 3 had elevated DHT. No patient had an elevated DHEA or A without an evelation of the other androgens. The control levels of DHEA-S were above normal in 45 patients; the DHT levels were elevated in 43 patients; 31 patients had elevated T levels; and 25 patients elevated A; and 24 patients, DHEA levels. In 32 patients with adequate suppression of adrenal androgens after 7 days of Dex administration, the source of excess androgens could be evaluated. Of 13 patients with elevated A levls, the excess A production was of adrenal origin in 6 cases, of ovarian origin in 5 cases, and of mixed origin in 2 cases. Of 15 patients with elevated T levels, the excess T production was of adrenal origin in 3 cases, of ovarian origin in 10 cases, and of mixed origin in the remaining 2 cases. Of 25 patients with elevated DHT levels, the excess DHT production was of adrenal origin in 16 patients, of ovarian origin in 5 patients, and of mixed origin in 4 patients. Of the 32 patients with an adequate Dex suppression test, 14 showed evidence of adrenal hyperandrogenism, 5 had ovarian hyperandrogenism, and mixed hyperandrogenism was present in the remaining 13 patients. There was an adrenal source of hyperandrogenism in 27 of 32 patients (14 pure adrenal and 13 mixed adrenal-ovarian), which represents 85% of the 32 patients.
Adolescent↗
Ovarian and adrenal contributions to peripheral androgens in hirsute women.
Serum levels of testosterone (T), 5alpha-dihydrotestosterone (DHT), androstenedione (A), dehydroepiandrosterone (DHEA), dehydroepiandrosterone-sulfate (DHEA-S), 17-hydroxyprogesterone (17-P), and cortisol (F) were measured in 33 hirsute women. Ten were hirsute and eumenorrheic (H-E), and 23 were hirsute and oligomenorrheic or amenorrheic (H-OA). Daily morning blood samples were obtained for 6 consecutive days. Dexamethasone (Dex), 2 mg/day was administered starting after venipuncture on the second day and continuing for 5 days. Human chorionic gonadotropin (hCG) was administered intramuscularly on the afternoon of the fourth and fifth days. The mean levels of all steroids measured under basal conditions in the hirsute women as a group were significantly elevated when compared to nonhirsute premenopausal women. Dehydroepiandrosterone-sulfate was the only steroid which showed significantly different mean levels between the two groups of hirsute women, being higher in the H-OA patients. Individual hirsute patients showed an elevated serum 17-P level as the most consistent finding; it was present in 90% of the patients in both groups. Significantly more H-E patients showed Dex-suppressible DHT (90% vs 40%; P less than 0.05) and A (70% vs 25%; P less than 0.05) than did H-OA patients. Dex-suppressibility of 17-P was observed in only 20% of the H-E and 15% of H-OA patients. A positive response to hCG was observed in all patients for serum 17-P and in about half or less of the patients for the other steroids. These dynamic tests of adrenal suppression and ovarian stimulation suggest that the ovary may be the main source of 17-P overproduction in both groups of patients. Although 17-P has been previously postulated to have androgenic activity, it is not yet known whether this steroid has a causal relationship to hirsutism.
Adrenal Glands↗
The applications of steroid hormone radioimmunoassays to clinical obstetrics.
This is a selective survey of recent publications dealing with theoretical and established applications of steroid hormone radioimmunoassay procedures applied to clinical obstetric investigation. This subject is reviewed in three sections: first, basic principles of steroid hormone radioimmunoassay methodology; second, steroidogenesis in normal pregnancy and its relation to patterns of steroid hormones measured in maternal and fetal circulations; third, applied steroid radioimmunoassay technology as it is being used in established and potential clinical applications. It is concluded that steroid hormone radioimmunoassay procedures have been and will continue to be a highly productive technology applied to clinical obstetric investigation.
Adrenal Cortex Hormones↗
Serum steroid levels following a large intravenous dose of a steroid sulfate precursor during the second trimester of human pregnancy. I. Dehydroepiandrosterone sulfate.
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Adolescent↗