In vivo blockade of the estradiol-binding-protein (EBP) by clomiphene citrate in human breast cancer.
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The authors studied the binding of steroids with Blastokinin (BKN). They confirm that progesterone is the steroid that has a greater affinity for BKN than estradiol or testosterone; the latter is hardly bound to the protein at all. They also show that the presence of estradiol interferes with the formation phase of the BKN-progesterone complex, while testosterone does not. When the BKN-progesterone complex is already formed, a release of the progesterone occurs only when there is a double concentration of estradiol. The biological importance of this phenomenon is briefly discussed.
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Hormonal control of progesterone and estradiol receptors was studied in the cytozol of short-lived culture of human endometrium in normal and undeveloping pregnancy. Endometrium was cultivated in the presence of estradiol or progesterone for 16 hours. In cultivation of normal endometrium with estradiol the content of estradiol receptors increased 4-fold in comparison with unstimulated tissue, and of progesteron receptors--3-fold. In cultivation of normal endometrium with progesterone the content of estradiol receptors rose 4--5-fold, and of progesterone receptors--3-fold. In cultivation of pathological endometrium with estradiol or progesterone the number of estradiol receptors was only doubled, and of progesterone receptors--increased only 1 1/2 times, this pointing to a diminished sensitivity of pathological endometrium to the regulating action of sex hormones.
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In patients with hypogonadism, the exact cause of the deficient androgenisation is not always clinically apparent. The data presented demonstrate that by means of hormone measurements, basally or after stimulation tests, the exact level of the lesion can usually be determined. This allows a decision with regard to appropriate therapy to be made on the basis of an accurate diagnosis. In many instances basal measurements of pituitary and gonadal hormones are all that is required to decide the level of the lesion. Care in interpreting basal levels is required, however, in view of methodological limitations and of known physiological variations with age, time of day and hour-to-hour fluctuations. If the basal hormone levels are borderline, or if the 'reserve function' of part or all of the hypothalamic-pituitary-gonadal axis needs to be assessed, than the appropriate stimulation test should be performed. The indication for these stimulation procedures and results obtained in different conditions are described and problems of interpretation discussed.
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Six women used polysiloxane vaginal rings impregnated with progesterone, or progesterone and estradiol. Nineteen 3-week treatment cycles were studied. Subjects kept records of bleeding. Plasma progesterone, estradiol, and gonadotropins were measured by radioimmunoassay. The patient acceptance was poor. None of the subjects experienced regular withdrawal bleedings during the treatment-free week. Fifty-three percent of the cycles were ovulatory as judged by plasma progesterone, but the plasma concentration of progesterone was low during the luteal phase. However, no pregnancies were discovered during the study period. Several high estradiol peaks were present during the treatment. Plasma LH fluctuated in the range of the normal menstrual cycle. Some suppression of plasma FSH was observed. The combination of estradiol and progesterone in the rings caused stronger suppression of FSH, but no diminution in the rate of ovulations or in disturbances of bleeding were observed in comparison to rings impregnated only with progesterone. Rings released the same amounts of progesterone in vitro and produced plasma concentrations which varied between 0.4 and 1.9 ng/ml.
The time course of free oestradiol and oestrone as well as of total (free and conjugated) oestrone was determined in plasma of women after oral ingestion of 3.75 mg conjugated equine oestrogens, or 9.74 micromol of oestrone sulfate, oestrone, and oestradiol, respectively. All these oestrogen preparations led to transiently increased plasma oestrogen levels which fell to normal values after 48 h. The main difference observed between administration of free oestrone or oestradiol and of conjugated oestrogens (oestrone sulfate or equine oestrogens) was a much more protracted influx of oestrogens from the intestine into the plasma compartment, with a tendency to more sustained plasma levels, if conjugated oestrogens were administered. There was a consistent discontinuity in plasma oestrogen levels 10--12 h after oral ingestion of all the preparations examined indicating enterohepatic circulation. Comparison of "areas under the curve" obtained with the present preparations to similar previous studies on ethinyl oestradiol indicated that the bioavailability of the non-ethinyl oestrogens is by more than one order of magnitude less than that of ethinyl oestradiol after oral administration. The ratio of oestrone/oestradiol was the highest with free oestrone and similar among the other three preparations indicating an increased metabolism of sulfoconjugated oestrone to oestradiol after oral application when compared with free oestrone.
The ovarian function of 20 healthy users of a levonorgestrel-releasing intrauterine device was studied by measurements of plasma estradiol, progesterone, and levonorgestrel concentrations. Eight subjects were amenorrheic, and 12 had regular menstrual bleeding. Seventy-five percent of the subjects in both groups had ovulatory cycles. There was no difference between the mean levonorgestrel concentrations in the amenorrheic and regularly menstruating subjects. Estradiol function was undisturbed in the amenorrheic subjects with ovulatory cycles. The effect of levonorgestrel as a cause of amenorrhea is thought to be mainly of local nature. The intrauterine administration of levonorgestrel had only an occasional and weak effect on ovarian function.
Abortion was performed by curettage on 71 women with pregnancies between the 7th and the 13th week of gestation seven to eight hours after intracervical application of a tylose gel containing 3mg prostaglandin F2 alpha. Prior to the application of the prostaglandin and immediately before the surgical intervention a sonographic examination for determining the vitality of the pregnancy was carried out.--Plasma progesteron, estradiol and HPL levels were determined radioimmunologically prior to the application of prostaglandin, at four-hour intervals on the day of intervention, and 24, 48 and 72 hours after the intervention. In 22 women a complete or an incomplete abortion occurred; in two cases a blighted ovum was observed; 47 pregnancies, according to sonographic examination, remained intact until curettage. After seven to eight hours duration of the effect of the prostaglandin gel, progesterone levels were found to be reduced to 60.5 per cent and 17-beta-estradiol to 31.4 per cent of the initial values, whereas the HPL values fell below the specificity of the testing procedure (12.5 ng/ml). Comparative investigations of the pregnancies which, according to sonographic findings, remained intact until curettage and those which were aborted after the application of prostaglandin did not, in spite of low plasma progesterone and estradiol levels in the abortive group, reveal any statistically significant differences. The abortive effect--even with local application--of the prostaglandins was confirmed. Conclusions regarding the effective mechanism of the prostaglandins upon the fetoplacental unit and the function of the corpus luteum remain subject to speculation.
The radioisotopic method of 131J-labelled albumin was employed to determine the distribution of acidic proteinase activity in some organs and tissues of chickens. The highest enzymatic activities were found in intestine wall, in pancreas, and in liver. Considerably lower activities were ascertained in kidneys, brain, lungs, and heart. The different proportions of these enzymes in homogenates and supernatant fractions (106 000 g) testify to a lack of uniformity in the solubility of cathepsins in the organs tested. The tested organs, with the exception of pancreas, did not show any enzymatic activity of neutral proteinases.