Estrogen and progesterone receptors in breast cancer.
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Biomedical subjects
Publications and source records attributed to R Vihko.
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Peripheral serum concentrations of FSH, LH, prolactin and ACTH were measured in 22 patients with advanced prostatic carcinoma treated by castration, polyestradiol phosphate (Estradurin) administration and a combination of castration and Estradurin administration during the first 12 months of treatment. Estradurin treatment alone (80 mg i.m.l once a month) did not result in any significant changes in the circulating concentrations of FSH, LH and prolactin. Therefore, the clear-cut inhibition of testicular steroidogenesis observed under this kind of treatment does not appear to be due to an inhibition of pituitary gonadotropin secretion, and is most likely due to a direct estrogen effect on Leydig cells. Castration led to grossly elevated serum FSH and LH levels. In this group, serum FSH remained at a high level, whereas LH was close to pretreatment levels 9 months after castration, suggesting differences in pituitary capacity to secrete FSH and LH under these conditions. Concentrations of circulating FSH, and to a lesser extent LH, in the combination treatment group were between those found in the castration and estrogen-only treatment groups, suggesting that the secretion of both gonadotropins can be suppressed by estrogen. No changes in serum prolactin and ACTH concentrations were seen in the three treatment groups.
We investigated the effects of digital prostatic palpation, cystoscopy, and biopsy of the prostate on the concentrations of serum prostate-specific acid phosphatase (PAP) measured by radioimmunoassay. Serum concentrations of PAP in patients with normal or hyperplastic prostates did not exceed the upper limit of our reference range (4 microgram per liter) during the 48 hr after digital prostatic palpation. The serum concentrations of PAP did not significantly increase in patients with carcinomatous prostates after digital examination of the prostate. Serum PAP did increase in patients with benign prostatic hyperplasia soon after cystoscopy of biopsy of the prostate. No diurnal variation in the serum concentrations of PAP during the follow-up of 48 hr was detected in the patient groups with normal, benign hyperplastic, or carcinomatous prostates not subjected to rectal examination.
We describe a receptacle for use in the simultaneous radioimmunoassay of two serum constituents in a single sample, and the application of this principle for the measurement of human pregnancy serum choriomammotropin and pregnancy-specific beta 1-glycoprotein. The analytical performance of this multicomponent radioimmunoassay approaches that of conventional radioimmunoassays. By following the principle described, it is likely that large numbers of constituents can be efficiently measured in single samples.
Serum LH, FSH, prolactin, oestradiol, testosterone, 5 alpha-dihydrotestosterone, androstenedione, androsterone, progesterone, 17-hydroxyprogesterone and cortisol concentrations were measured in a pubertal boy suffering from gynaecomastia. At birth he had hypospadias, a scrotal anomaly, an abnormally small penis and unilateral cryptorchidism. At puberty, a small ejaculate volume with normal sperm concentration was recorded. Under basal conditions the serum concentrations of testosterone, oestradiol, 5 alpha-dihydrotestosterone, 17-hydroxyprogesterone and androsterone were clearly above normal, and they were not suppressed by dexamethasone as was the serum cortisol, which also showed normal diurnal variation. This suggested that the overproduction of sex steroids was of testicular origin. The serum LH was also elevated under basal conditions, while the serum FSH was in the reference range. The serum LH was not suppressed by ethinyl oestradiol administration, as the serum FSH was. The clinical observations and endocrine data are interpreted as indicating a partial failure in androgen action, responsible for the genital abnormalities observed and the deficiency in the hypothalamo-pituitary regulation of gonadotropin secretion, and are indicative of the findings described in connection with an unusual form of incomplete male pseudohermaphroditism type 1.
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The radioimmunoassay of human prostate-specific acid phosphatase and the measurement of the catalytic activity of acid phosphatase using p-nitrophenyl phosphate as substrate were compared in the diagnosis and follow-up of therapy of prostatic cancer patients. We monitored 17 patients without metastases and eight patients with metastases for 12 months. We detected elevation of the catalytic activity of acid phosphatase [the upper limit for the reference range was mean + 2 (S.D.)] in 24% of the sera of all these patients (n = 25), and the concentration of prostate-specific acid phosphatase measured by radioimmunoassay [the upper limit for the reference range was mean + 3 (S.D.)] was elevated in 80% of these samples before therapy. The radioimmunological measurement of prostate-specific acid phosphatase was therefore more efficient in detecting prostatic cancer than was measurement of the catalytic activity. Favorable effects of the various forms of endocrine treatment were detected more clearly by the measurement of immunoassayable prostatic acid phosphatase than by the measurement of catalytic activity. Activation of the disease during various forms of endocrine treatment of prostatic carcinoma is possibly more efficiently signaled by radioimmunoassay than by measurement of catalytic activity.
Twenty patients with advanced or recurrent endometrial adenocarcinoma were treated with combination chemotherapy consisting of Adriamycin, cyclophosphamide, 5-fluorouracil, and vincristine at three-week intervals. A minimum of four treatment courses was given in each case. There were five total and five partial responses (50% favorable response rate); progression of the disease was evident in seven cases (35%). Lung metastases responded significantly better (P < 0.01) than other lesions: seven out of nine lung metastases showed an objective remission, whereas only two out of 11 tumors in pelvic, abdominal, or retroperitoneal space responded. The response rate did not correlate with histologic grade of tumor differentiation, or the performance state and age of the patient. Cytosol estrogen and progestin receptor levels were measured in 15 cases from the carcinomatous endometrial tissue prior to therapy. Ten patients with low receptor values (estrogen and/or progestin receptors below 30 fmol/mg cytosol protein) had a significantly (P < 0.025) greater response rate (70%) than did patients with higher receptor values (both receptors above 30 fmol/mg protein, response rate 20%). Determination of only one of the two receptors did not differentiate the patients equally well, although the response rate tended to be better (0.05 < P < 0.1) in patients with a low level of either estrogen or progestin receptor (67% response rate) when compared with a 33% response rate in patients with a high level of the corresponding receptor. Our results suggest that the measurement of cytosol steroid hormone receptors has the potential to serve as a suitable indicator for selection of endocrine or nonhormonal chemotherapy for patients with advanced endometrial adenocarcinoma.
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The therapeutic efficacy, plasma levels, and psychomotor effects of tryptophan (L-tryptophan), clomipramine hydrochloride, and doxepin were investigate in "neurotically" depressed outpatients. The tricyclic antidepressants were significantly more efficacious than tryptophan in inducing remission. The alleviation of depression was preceded by an improvement of the initially slow information-processing rates in the depressed patients. The plasma levels of the tricyclics that were associated with a therapeutic response were significantly lower than those reported in "endogenously" depressed inpatients.
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LH/hCG binding and concentrations of pregnenolone, progesterone, 17-hydroxy-progesterone, androstenedione, testosterone and 5 alpha-dihydrotestosterone were measured in testicular tissue obtained from patients undergoing orchiectomy for prostatic cancer. One group of the orchiectomized patients had received an injection of 80 mg polyestradiol phosphate 1-9 days before the operation, another group were treated with monthly injections of the oestrogen for several months, and the remainder were not treated with oestrogen. In non-oestrogen treated patients (n = 8) the hCG-binding capacity was 28.0 +/- 15.0 (SD) ng/g and the equilibrium association constant of binding was 0.69 +/- 0.38 x 10(10) M-1. The binding capacity was significantly (P less than 0.025) lower (10.3 +/- 8.7 ng/g) in patients (n = 6) receiving the first oestrogen injection 3-9 days prior to the operation. A further decline to the level of 1.77 +/- 1.03 ng/g occurred in patients (n = 3) treated over 3 months with the oestrogen injections. At the same time, no significant changes were observed in peripheral serum LH and FSH levels. In the testicular endogenous steroid levels, statistically significant decreases were seen 9 days after the oestrogen injection in pregnenolone (from 505 +/- 315 ng/g to 138 +/- 86 ng/g) and in testosterone (from 669 +/- 243 ng/g to 254 +/- 49 ng/g) whereas no significant changes could be seen in the levels of the other steroids analysed. This study gives further evidence for the direct inhibitory action of oestrogens on human testicular steroidogenesis and suggests that the loss of testicular luteinizing hormone receptors may be one facet of this inhibitory action.
The concentrations of testosterone, four of its precursors (pregnenolone, progesterone, 17 alpha-hydroxyprogesterone, and androstenedione), and three of its metabolites (5 alpha-dihydrotesterone, 5 alpha-androstane-3 alpha, 17 beta-diol, and androsterone) were measured in the epididymis and proximal ductus deferens of elderly men with prostatic carcinoma. In addition, they were measured in testis tissue and spermatic and p eripheral blood sera.l The main androgen in the epididymis was testosterone [37.3 +/- 22.0 (SD) ng/g wet tissue]; 5 alpha-dihydrotestosterone was also present in a relatively high concentration [9.7 +/- 6.5 (SD) ng/g wet tissue]. There were no steroid concentration gradients along the epididymis. The actual and relative concentrations of the steroids measured strongly suggest that they are transferred from testes to epididymides in the testicular lymph or rete testis fluid. Estrogen administration led to significant decreases in epididymal androstenedione, testosterone, and 5 alpha-dihydrotestosterone concentrations. Thus, one facet of the deleterious effects of estrogen on male reproductive functions may be interference with normal epididymal function, essential for undisturbed sperm maturation.
Wedge resection was performed in 12 patients with polycystic ovarian disease, and cell samples from the cystic follicles were assayed for LH(hCG) receptor using [125I]iodo-hCG as a ligand hormone. Simultaneously to wedge resection, blood samples were taken for serum FSH, LH, 17 beta-estradiol, progesterone, and testosterone RIA measurements. Serum LH was regularly elevated (16.0-57.1 U/liter), whereas FSH (5.2-11.5 U/liter) was within the normal reference range. The LH to FSH ratio was between 2.1-7.8. The 17 beta-estradiol concentrations (0.12-0.23 nmol/liter) were within the normal reference range found during the early follicular phase. Only 3 patients had progesterone levels exceeding the assay sensitivity limit of 0.1 nmol/liter. Ony 3 of the 11 patients assayed for serum testosterone had values exceeding the upper limit of the reference range. Seventy-seven percent of the ovarian follicular samples showed specific binding of [125I]iodo-hCG. The number of receptors in positive samples averaged 0.67 +/- 0.11 fmol/mg homogenate protein, which is clearly lower than that in normal preovulatory follicles. Scatchard analyses revealed a single class of binding sites, with a mean equilibrium association constant of 5.4 X 10(9) M-1 at 37 C. These results suggest that the derangement of follicular development in patients with polycystic ovarian disease probably is not due to the lack of appearance of the LH(hCG) receptor. It is possible that the tonic elevation of serum LH results in a decrease in the number of available receptor sites; this would be one step in the process leading to ovarian changes characteristic of this disease.
The metabolism of a new synthetic progestagen, Org 2969 was studied in 4 healthy female volunteers. During the first part of the study (Phase I), the volunteers ingested 50 microgram (about 0.1 mCi) of [16-3H5Org 2969 together with 50 microgram of ethinyloestradiol as a single dose. During the second part of the study (Phase II), a 10-day pre-treatment with the same dosage of non-radioactive compound preceded the administration of the radioactive steroid. A peak level of total radioactivity, representing 3.16-5.02% of the dose given/l of serum, was achieved within 2-3 h in Phase I. During Phase II, the corresponding figures were 4.54-5.13% after 1.5-3 h. The difference was mainly due to an increase of freely-extractable steroids during Phase II. The difference can at least partly be explained by assuming a change in the kinetics of the metabolism of Org 2969 by pre-treatment with Org 2969 and ethinyloestradiol. The mean recovery of radio activity in urine and faeces was 83.0%/48.1%/34.9% (total/urine/faeces) of the total dose in Phase I and 76.1%/45.2%/30.9% during Phase II. The differences in the total excretion and in the radioactivity excreted in the faeces were significant.
The iron stores of 32 healthy pregnant women were evaluated longitudinally during pregnancy and 6 months post partum by serum ferritin assay and by bone marrow iron content. Half of the women were receiving oral iron while the others were not given iron supplementation. Women receiving iron could maintain their iron stores throughout the pregnancy. By contrast, women without iron therapy had low serum ferritin values, pointing to the absence of iron stores during the last trimester, and 6 of these 16 women developed anemia. This was confirmed by estimation of the quantity of stainable iron in the bone marrow. In addition serum iron, transferrin and red cell MCV values indicated iron deficient erythropoesis. During a 6-month period after pregnancy the women receiving supplemental iron during pregnancy had a significant increase in their serum ferritin concentrations, indicating restoration of iron stores. Women not receiving iron during pregnancy had exhausted iron stores at term and serum ferritin values stayed low even at 6 months after delivery. If iron therapy was instituted after parturition, serum ferritin assays indicated restoration of iron stores within the ensuing 6 month. To prevent iron deficiency anemia during pregnancy supplemental iron is advisable for all pregnant women in our country.