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Biomedical subjects

J E Buster

Publications and source records attributed to J E Buster.

At least 109 records · Page 6Linked to original sources

Androstenedione, testosterone, and estradiol concentrations in fetal and maternal plasma in late pregnancy in the sheep.

Fetal and maternal plasma concentrations of androstenedione, testosterone, and estradiol were measured in chronically catheterized pregnant sheep during late gestation, spontaneous term delivery, and premature delivery induced by the infusion of low doses of synthetic ACTH-(1-24) (ACTH) to the fetus at 120-130 days gestation. RIAs employing two different antisera directed at different sites of each molecule were used in combination with Celite column chromatography to ensure the specificity of the hormone measurements. Fetal plasma concentrations of all three hormones were greater than the respective maternal concentration at all periods investigated, except immediately before ACTH-induced delivery when fetal testosterone and estradiol concentrations were lower. These observations further support the hypothesis that delivery in the sheep is associated with the induction of placental 17 alpha-hydroxylase and 17,20-lyase by the increased conversion of progesterone to estrogens. The higher values of androstenedione than of testosterone also support the view that estrone is produced in larger quantities than estradiol and that estrone and estrone sulfate are good endocrine markers of the progress of the endocrine changes occurring immediately before parturition in the sheep.

Androstenedione↗

Oxytocin and prolactin responses in long-term breast-feeding.

Plasma levels of oxytocin and prolactin were measured before and during 12 minutes of breast pump stimulation in five healthy, lactating, amenorrheic women on three occasions: ten to 90 days post partum, 90 to 180 days post partum, and 180 days to one year post partum. Baseline mean (+/- SEM) plasma oxytocin levels were similar in the three study periods. Mean stimulated plasma oxytocin levels increased in the three study periods (each P less than .001; mean baseline versus stimulated). Stimulated plasma oxytocin values were significantly greater at ten to 90 than at 90 to 180 days (P less than .05; analysis of variance). Baseline serum prolactin levels were 61 +/- 9.5, 36 +/- 8.6, and 33 +/- 10.8 ng/ml, respectively (not significant; one-way analysis of variance). Mean stimulated prolactin levels were 71 +/- 8.1, 43 +/- 4.5, and 43 +/- 2.8 ng/ml, respectively (not significant). Thus, the oxytocin secretory reflex continues in long-term lactation for the first year post partum. In addition, breast stimulation in long-term lactating women continues to produce a slight increase in serum prolactin levels.

Adult↗

Hypothalamic-pituitary-adrenocortical function during long-term low-dose dexamethasone therapy in hyperandrogenized women.

Hypothalamic-pituitary-adrenocortical (H-P-A) function was tested in 14 hyperandrogenized women, aged 17 to 32 years, who had been continuously treated with nightly single-dose oral dexamethasone, 0.25 to 1.00 mg, for 3.7 to 16.5 months. Daily AM serum cortisol concentrations were measured in nine subjects after discontinuation of dexamethasone. Basal cortisol concentrations returned to normal (greater than or equal to 6.0 micrograms/dl) within 36 hours in 67%, within 60 hours in 89%, and within 84 hours in 100%. Median time to return to normal was between 12 and 36 hours. Rate of return correlated with both the dose-adjusted duration of dexamethasone therapy (p less than 0.01) and the degree of adrenocortical suppression during treatment (p less than 0.01). The H-P-A response to insulin-induced hypoglycemia and the adrenal response to an acute intravenous adrenocorticotropic hormone (ACTH) challenge were evaluated in eight subjects 12 to 36 hours after the final dexamethasone dose. Thirty-eight percent demonstrated normal cortisol increments to hypoglycemia, 25% had blunted or absent cortisol responses to hypoglycemia but normal cortisol increments to exogenous ACTH, and 38% had blunted or absent responses to both hypoglycemia and exogenous ACTH. The responsiveness of the H-P-A axis correlated with the degree of adrenocortical suppression (p less than 0.05) but not with dose of dexamethasone or duration of treatment. Small doses of dexamethasone are not necessarily "physiologic", but dexamethasone therapy with maintenance of serum cortisol levels greater than or equal to 2.0 micrograms/dl was associated with rapid return to normal basal cortisol concentration and a normal cortisol response to insulin-induced hypoglycemia.

Adolescent↗

Time trend analysis of plasma unconjugated and sulfoconjugated estrone and 3 beta-delta 5-steroids in fetal and maternal sheep plasma in relation to spontaneous parturition at term.

Parturition in the sheep is preceded by a complex series of changes in both fetal and maternal plasma-steroid hormone concentrations. Using the chronically catheterized fetal sheep preparation, we measured unconjugated and sulfoconjugated pregnenolone, 17 alpha-hydroxypregnenolone, dehydroepiandrosterone, and estrone in fetal and maternal plasma over the final 20 days before spontaneous vaginal delivery at term. Where appropriate, third degree polynomial functions were fitted to the changing plasma hormone concentration profile. Fetal and maternal plasma pregnenolone and pregnenolone sulfate both fell from maximum values in the last 4 days of gestation. Fetal and maternal plasma estrone and estrone sulfate concentrations underwent a terminal rise over the last 4 days of gestation that was a mirror image of the fall in plasma pregnenolone and pregnenolone sulfate. Maternal 17 alpha-hydroxypregnenolone rose over the last 4 days of gestation. Fetal 17 alpha-hydroxypregnenolone, maternal and fetal plasma dehydroepiandrosterone sulfate, and fetal plasma dehydroepiandrosterone sulfate, and fetal plasma dehydroepiandrosterone showed no trend during the period of study. Maternal plasma dehydroepiandrosterone rose over the last 4 days of gestation. These results support the view that increased activity of placental 17 alpha-hydroxylase and 17-20-desmolase is responsible for the conversion of C-21 steroids to estrogens at term. delta 5-Steroids are present in very high plasma concentrations in fetal sheep plasma and may constitute a more important precursor pool for estrogen biosynthesis than does circulating plasma progesterone.

17-alpha-Hydroxypregnenolone↗

Changing patterns of steroid production in the fetus and placenta and their effects on development.

A variety of radioimmunoassays specifically characterized for use with fetal and maternal ovine plasma have been used to measure steroid hormone concentrations in small plasma samples drawn simultaneously from mother and fetus. By repeated sampling from the same animal preparation the changes over time of plasma concentrations of cortisol, pregnenolone and its sulphate, and oestrone and oestrone sulphate have been systematically studied. In animals delivering spontaneously at term the fetal plasma cortisol concentration rises between 120 and 130 days gestation and plays an important part in the maturation of several vital physiological systems, including the fetal thyroid axis. In normal term deliveries and premature deliveries induced by synthetic adrenocorticotropin (ACTH(1-24), 1 microgram h-1), the concentration of oestrone sulphate in maternal plasma increases before the fetal plasma concentration. Fetal and maternal oestrogens are probably important in the control of the low-grade tonic myometrial activity that occurs throughout gestation, in the initiation of labour and in the control of uterine blood flow. Low-grade tonic myometrial activity affects fetal oxygenation, fetal breathing and the fetal sleep state and may constitute a pathway through which the mother influences fetal development, with important physiological and possibly pathological consequences.

Adrenal Glands↗

A combined radioimmunoassay for the measurement of unconjugated and sulfoconjugated pregnenolone, 17 hydroxypregnenolone, dehydroepiandrosterone, and estrone applied to fetal and maternal ovine plasma.

This report describes a radioimmunoassay (RIA) method for the combined measurement of four steroid sulfoconjugates and their four unconjugated counterparts in maternal and fetal ovine plasma: pregnenolone (delta 5P), 17-hydroxypregnenolone (17 delta 5P), dehydroepiandrosterone (DHEA), and estrone (E1). In the procedure a preliminary ether extraction is utilized to isolate the unconjugated steroids followed by salting out, ethyl acetate extraction, and mineral acid solvolysis of the remaining sulfated steroids. The hydrolyzed sulfoconjugates are then separated chromatographically and measured in a manner identical to their unconjugated counterparts. The combined measurement of these eight steroids in single samples of fetal and maternal ovine plasma has not been reported previously and plasma concentrations of these steroids were heretofore unknown. Since no previous data was available for comparison, rigorous specificity evaluation of this RIA system was required prior to its use for physiologic studies and the reporting of concentrations in this species.

17-alpha-Hydroxypregnenolone↗

Dexamethasone suppression test in the management of hyperandrogenized patients.

The authors evaluated 86 hyperandrogenized women with measurements of serum cortisol, dehydroepiandrosterone sulfate, testosterone, and dihydrotestosterone in pooled sera before and after a dexamethasone suppression test. According to strict criteria, 70 (81%) of 86 women demonstrated a major glucocorticoid-suppressible component to their hyperandrogenism. Endocrine therapy was dictated by the results of the dexamethasone suppression test. To assess the predictive value of this test, we evaluated the clinical responses of the subgroup of 55 women who received appropriate endocrine suppression therapy for 6 to 15 months. Of this subgroup, 38 were identified as having adrenal hyperandrogenism; 3 had ovarian hyperandrogenism; and 14 had mixed hyperandrogenism. Of the 55 patients, 49 received dexamethasone alone; 3 received dexamethasone plus Ovral (an oral contraceptive containing the synthetic progestogen norgestrel 0.5 mg and ethinyl estradiol 0.05 mg); and 3, all with ovarian hyperandrogenism, received depomedroxyprogesterone acetate (Depo-Provera). Clinical response was assessed in terms of improvement or no improvement in menstrual status, acne, and hirsutism. Of 29 patients with adrenal or mixed hyperandrogenism associated with abnormal menses, the menstrual status of 17 (59%) improved after dexamethasone therapy. Acne improved in 39 (100%) of 39 subjects. Hirsutism showed moderate to marked improvement in 40 (73%) of 55 women after 6 to 15 months of endocrine suppression therapy. These results indicate the endocrine suppression therapy, particularly with repeated low-dose dexamethasone, prescribed on the basis of a dexamethasone suppression test, is an effective means of managing hyperandrogenism.

Adolescent↗

Time-trend analysis of plasma cortisol concentrations in the fetal sheep in relation to parturition.

Using a cortisol RIA carefully validated for specificity in fetal ovine plasma, we studied plasma cortisol time-trend changes in eight chronically catheterized sheep fetuses in the last 22 days of gestation before the spontaneous onset of labor. Best fit exponential type curves were drawn for each individual fetus to define the time before the onset of labor at which fetal plasma cortisol was rising at different rates. Fetal plasma cortisol increased at a rate of 0.5 ng ml-1 day-1 as early as 17.1 days before labor in one fetus, whereas the mean value for all eight fetuses occurred 11.8 +/- 1.0 (SEM) days before labor. The rate of increase doubled to 1.0 ng cortisol ml-1 day-1 as early as 14.4 days before labor in one fetus, whereas the mean value for all eight fetuses occurred 9.3 +/- 0.9 days before labor. These findings suggest that the regulatory mechanisms responsible for the prelabor increase in fetal cortisol production are activated earlier in gestation than we previously thought.

Animals↗

Responsiveness and maximum secretory capacity of isolated fetal lamb adrenocortical cells throughout the last third of gestation.

Although considerable evidence implicates increased fetal adrenal function as a major factor in the initiation of parturition in the sheep, the mechanism responsible for this increased activity has not yet been determined. We have investigated the development of the function of fetal lamb adrenal cortical cells dispersed in vitro. There was no change in the sensitivity of the cells to synthetic ACTH (ACTH1-24), as demonstrated by the concentraton of ACTH1-24 producing a 50% maximum response in corticoid secretion. This finding does not support the suggestion that there is a qualitative change in fetal adrenal receptor function as term approaches. No stimulation of corticoid was observed after the administration of alpha MSH or PRL in vitro at any gestational age or of alpha MSH in vivo in four fetuses at 125--130 days gestation. Both the maximum output and the 50% maximum response in corticoid secretion of adrenal cells from term fetuses were similar to those of adrenal cells from adult ewes. A significant increase in the maximum output of corticoids per cell in response to ACTH1-24 occurs as early as 107 days gestation and continues steadily to term.

Adrenal Cortex↗

Fetal adrenal cortex.

The fetal adrenal cortex is the central steroid modulator in the fetal placental complex. Its anatomic structure and physiology clearly identify it as a uniquely fetal organ that undergoes atrophy to a fraction of its intrauterine size after birth and assumes markedly different steroidogenic functions on the assumption of extrauterine life. Its importance as a regulator of maturation and parturition in normal gestation is just being understood. The fetal adrenal cortex no doubt plays major roles in the pathogenesis of some of the most important clinical problems currently faced in contemporary obstetrics. Continued research that provides a more complete understanding of this organ will serve as the major base for innovative diagnostic and therapeutic advancements of the future.

Adrenal Cortex↗

Bromocriptine in the treatment of premenstrual tension syndrome.

Twenty-four women with regular cycles who reported moderate to severe premenstrual tension participated in a double-blind study to test the effectiveness of CB154 on the control of their symptoms. Symptoms were scored daily and were further evaluated objectively twice monthly by physical examination. Control cycle follicular/luteal delta weights were not different statistically from a 0 change (P > .10), despite long-standing symptoms of bloating, swelling, and reported weight gain. CB154 treatment resulted in statistically significant improvement in daily ratings of breast tenderness (P < .005), bloating (P < .02), and depression (P < .05). Significant placebo effects observed for several other symptoms emphasize the psychologic component of this condition as well as the need for caution in the interpretation of any uncontrolled trials for therapies thought effective in the treatment of this disorder.

Adolescent↗

An algorithm for determining gestational age from unconjugated estriol levels.

Between the 30th and 40th weeks of gestational age (GA), plasma unconjugated estriol (E3) concentrations plotted as a logarithmic function of GA describe a complex bimodal curve. The maximum concentrations for the first peak (GAmax1) occur at approximately 34 weeks' GA, those for the second peak (GAmax2) occur at approximately 38 weeks' GA, and a between-mode nadir occurs at 35 weeks' GA. Using the close relationship between the features of this curve and GA, a computerized algorithmic curve analysis is devised for the estimation of GA during the third trimester of pregnancy. This report describes the algorithm, its clinical application, and its preliminary performance.

Computers↗

Time trend analysis of unconjugated estriol concentrations in third-trimester pregnancy.

Utilizing a plasma pooling procedure to control short-term pulsatile variability of unconjugated estriol (E3) concentrations, the authors evaluated time trend curves in 42 subjects after normalizing time trend curves in 42 subjects after normalizing gestational age (GA) by a computerized algorithm. Semilogarithmic plots from individual subjects and a median plot derived from pooling the 42 subjects describe complex bimodal curves beginning with an initial steep rise at 30 to 32 weeks' GA, a peak between 32 and 34 weeks' Ga, a transient nadir at 35 weeks' GA, a second steep rise between 35 and 37 weeks' Ga, a second peak between 37 and 39 weeks' Ga, and a downward segment just prior to parturition. Predicted GAs at delivery obtained from individual curve analyses concurred with pediatric GAs within 2 weeks or less in 41 or 42 pregnancies.

Estriol↗