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Biomedical subjects

R Vihko

Publications and source records attributed to R Vihko.

At least 145 records · Page 8Linked to original sources

Androgen concentrations in epithelial and stromal cell nuclei of human benign prostatic hypertrophic tissues.

Prostate tissues removed from patients with benign prostatic hypertrophy were separated into epithelial and stromal components and nuclei purified from these. The concentrations of testosterone, 5 alpha-dihydrotestosterone, 5 alpha-androstane-3 alpha,17 beta-diol, 4-androstene-3,17-dione, 5 alpha-androstanedione and androsterone in pooled preparations of the purified nuclei were determined by radioimmunoassays after the purification of solvent steroid extracts by Lipidex-5000 column chromatography. The most abundant androgen measured was 5 alpha-dihydrotestosterone and it was significantly (P less than 0.05) more concentrated in the stromal nuclei than in the epithelial nuclei. The mean concentration of androsterone was also significantly (P less than 0.05) greater in the stromal nuclei whereas that of testosterone was equal in the two nuclear types. The concentrations of 5 alpha-androstane-3 alpha,17 beta-diol, 4-androstene-3,17-dione and 5 alpha-androstanedione were below the sensitivity limits of the assays in the majority of cases, but the results indicated that when detectable the first two were more concentrated in the stromal than the epithelial nuclei. The results emphasize the importance of the prostatic stroma in androgen metabolism, and the relative concentrations of 5 alpha-dihydrotestosterone and testosterone indicated identical 5 alpha-reductase activities in the nuclei in comparison with respective whole cell epithelial and stromal preparations. 5 alpha-Dihydrotestosterone concentrations were clearly higher than the nuclear androgen receptor levels previously reported from this laboratory.

Androgens↗

Endocrine and metabolic effects of low-dose estrogen-progestin treatment in climacteric women.

In a double-blind clinical trial with 31 premenopausal women suffering from climacteric symptoms, 16 (group A) were treated with an estrone (sodium estrone sulfate 1.5 mg)-norethisterone (5 mg) combination, and 15 (group B) were treated with an estrone-megestrol acetate (5 mg) combination. These treatments effectively alleviated climacteric symptoms without causing any bleeding disorders or pathological changes in the cytology of the uterine cervix or endometrium. In groups A and B, respectively, postovulatory progesterone concentrations above 5 nmoles/liter were found in six and five patients before, in five and seven patients during, and in two and four patients after the treatments. Serum levels of luteinizing and follicle-stimulating hormones decreased significantly and testosterone decreased slightly during both treatments. Serum cholesterol (P less than .01) and high-density lipoprotein cholesterol(P less than .001) in group A decreased during the treatment; only the high-density lipoprotein cholesterol values (P less than .05) decreased in group B. Because of the minor endocrine and metabolic changes without any significant difference between the progestins, both norethisterone acetate and megestrol acetate seem to be suitable for estrogen-progestin combinations aimed at alleviating climacteric symptoms.

Adult↗

Cytosol and nuclear estrogen and progestin receptors and 17 beta-hydroxysteroid dehydrogenase activity in normal and carcinomatous endometrium.

Endometrial estrogen and progestin receptors were quantitatively measured in the cytosol (ERc, PRc) and nuclear (ERn, PRn) fractions, the activity of 17 beta-hydroxysteroid dehydrogenase measured in 13 normal women in the late proliferative phase of the cycle (control group), in 33 patients with adenocarcinoma, and in 6 patients with other malignancies of the endometrium. The parameters measured had relatively small variations in the control group, whereas the opposite was true for the malignant endometrium. ERc and PRc were present in significantly higher concentrations in normal endometrial tissue (167 and 1697 fmol/mg cytosol protein, respectively) than in malignant endometrial tissue (45 and 116 fmol/mg cytosol protein, respectively), and the ratios of ERc/ERn and PRc/PRn were higher (P much less than .001 in both cases) in the normal group. The activities of 17 beta-hydroxysteroid dehydrogenase were identical in normal and adenocarcinoma tissue and correlated with PRc in carcinomatous endometrium. The present results support previous findings that the great majority of endometrial adenocarcinoma specimens have significant concentrations of ERc and PRc and that these concentrations are lower than in normal endometrium. In addition, they demonstrate that nuclear location of the female sex steroid receptors is favored in the malignant tissue. Despite these differences, the 17 beta-hydroxysteroid dehydrogenase activities were identical in proliferative endometrium and in endometrial adenocarcinoma.

17-Hydroxysteroid Dehydrogenases↗

Clinical significance of estrogen and progestin receptors in ovarian cancer.

Concentrations of cytosol estrogen and progestin receptors were determined in ovarian carcinoma samples from 84 patients with early (stages I to II; N = 17), advanced (III to IV; N = 39), recurrent epithelial (N = 9), and nonepithelial (N = 5) cancer and with ovarian metastases of other malignancies (N = 11). Seventy-one percent of all the specimens contained estrogen and progestin receptors (3 or more and 6 or more fmol/mg cytosol protein, respectively, receptor-positive group), whereas 10% of the tumors were receptor-negative. Primary epithelial ovarian carcinomas were more often receptor-positive (81% versus 44%), and they had higher receptor concentrations than recurrent epithelial ovarian tumors. Primary endometrioid and serous carcinomas had higher concentrations of cytosol estrogen receptors than did mucinous tumors. Anaplastic endometrioid malignancies had significantly lower concentrations of both receptors than the differentiated tumors, whereas in serous carcinomas only cytosol progestin receptor displayed this difference. Patients with advanced malignancy characterized by low estrogen and/or progestin receptor concentrations had nonremovable tumor more often, and they survived for a shorter time than the other patients.

Adult↗

Cytosol estrogen and progestin receptors in endometrial carcinoma of patients treated with surgery, radiotherapy, and progestin. Clinical correlates.

Cytosol progestin (PR) and estrogen receptor (ER) concentrations were measured in 114 endometrial carcinoma specimens from 109 patients; these levels were correlated with clinical and histopathologic characteristics, and with clinical outcome in 44 patients followed for at least two years after the primary therapy consisting of surgery, irradiation and adjuvant administration of progestin. Eighty percent of all specimens were simultaneously PR- and ER-positive (greater than or equal to 6 fmol and greater than or equal to 3 fmol/mg protein, respectively) whereas 10% were both PR- and ER-negative. Early clinical stages (I and II) were more often receptor-positive, and the receptor concentration in these tumors was higher than in advanced or recurrent disease. The same was the case for superficial as compared with deeply invasive lesions. Both PR and ER concentrations in well or moderately differentiated tumors were higher than in anaplastic carcinomas. PR and ER concentrations did not correlate with the age of menopausal status, body weight or carbohydrate metabolism of the patients. In the patient group followed up for two years or more, the receptor-poor tumors tended to behave more aggressively than did receptor-rich malignancies in relation to patient survival. The measurement of PR and ER concentrations in advanced endometrial carcinoma has been proved useful in the selection of hormonal or cytotoxic chemotherapy. The current results advocate their use of prognostic risk factors which might be useful in selection of the most efficient treatment modalities for individual patients.

Adult↗

Serum sex steroid and peptide hormone concentrations, and endometrial estrogen and progestin receptor levels during administration of human leukocyte interferon.

Five normally cycling healthy women were given daily subcutaneous injections of human leukocyte interferon (3 X 10(6) units/day) from the 3rd through 23rd day of the menstrual cycle, and serum steroid and peptide hormone concentrations monitored at 3-day intervals during the treatment and the preceding control cycle. Concentrations of cytosol and nuclear estrogen receptors (ERC and ERN, respectively) and progestin receptors (PRC and PRN) were also measured from endometrial biopsies taken on the 24th day of the control and treatment cycle. In addition, an extensive monitoring of clinical chemical and hematological tests from the blood samples were performed. Serum estradiol and progesterone concentrations were significantly decreased during the treatment cycle, suggesting that interferon interacts in vivo with the function of both FSH and LH. No significant changes were observed in the serum peptide hormone concentrations measured (FSH, LH, prolactin, insulin, growth hormone and TSH); neither were the levels of endometrial ERC, ERN, PRC and PRN affected by interferon administration. As expected, interferon administration resulted in decreased leukocyte counts. Moreover, an increasing tendency in the activities of serum alkaline phosphatase and gamma-glutamyltransferase during the interferon therapy shows that interferon may slightly interfere with the liver function. These results suggest that one of the mechanisms by which interferon treatment may affect the growth of hormone-dependent neoplasms could be the interaction with production and/or function of circulating hormonal compounds.

Adult↗

Rapid endocrine effects of tamoxifen and testolactone in prostatic carcinoma patients.

The short-term (6-day) endocrine effects of tamoxifen and testolactone were investigated in men with prostatic carcinoma. Tamoxifen treatment (20 mg/day) did not affect the gonadotropin levels, but it temporarily increased prolactin, induced sex hormone-binding globulin production, and suppressed peripheral serum progesterone, 17-hydroxyprogesterone, androstenedione, testosterone, and 5 alpha-dihydrotestosterone concentrations. These changes were attributed to the estrogenic properties of tamoxifen, since no changes in peripheral serum estradiol concentrations were observed. Testolactone (1000 mg/day) decreased peripheral estradiol concentrations by 50% and increased the concentrations of the neutral steroids measured. The increases in serum FSH and LH were very small. This study corroborates the early estrogen-like action of tamoxifen, and the experiment with testolactone further suggests that endogenous estradiol has physiological functions in man, regulating gonadotropin and androgen production.

Aged↗

Rapid and slow response of human testicular steroidogenesis to hCG by measurements of steroids in spermatic and peripheral vein blood.

The effects of human chorionic gonadotropin (hCG) on testicular steroid secretion were studied in men during operation upon inguinal hernia. To investigate the rapid testicular response, we drew blood samples from peripheral and spermatic veins at the beginning of the operation, then gave an intramuscular injection of 5000 I.U. of hCG, and took another set of blood samples 30 min after injection. The slow testicular response to hCG was evaluate by taking samples from spermatic and peripheral veins 4 days following hCG administration. The operation alone led to a significant decrease in spermatic vein levels of pregnenolone, progesterone, 17-hydroxyprogesterone, androstenedione and testosterone in 30 min. Testicular steroidogenesis responded rapidly to hCG stimulation, which was reflected in elevated spermatic vein levels of pregnenolone, progesterone, 17-hydroxyprogesterone, androstenedione, testosterone and 5 alpha-dihydrotestosterone at 30 min following hCG. In peripheral vein, the concentrations of pregnenolone, progesterone and 17-hydroxyprogesterone were significantly elevated at the same time. Four days following hCG administration, the peripheral serum concentrations of 17-hydroxyprogesterone, testosterone, 5 alpha-dihydrotestosterone and estradiol were significantly increased. In spermatic vein, the steroids released after 4 days suggested a preferential release of C19 steroids and estradiol. Our results directly demonstrate that the human testis is able to respond rapidly to hCG stimulation. The first effect of hCG might be general facilitation of C21 and C19 steroid release to the circulation. Four days after hCG stimulation, the secretion of C19 steroids (including testosterone) and estradiol seems to be preferred, with a relative decrease in the release of C21 steroids.

Adult↗

Secretion into and elimination from blood circulation of prostate specific acid phosphatase, measured by radioimmunoassay.

The concentration of prostate specific acid phosphatase (PAP) was significantly higher in serum specimens from prostatic venous plexus blood than from peripheral venous blood in 6 patients operated upon because of benign prostatic hypertrophy. This suggests that normally circulating PAP is secreted via the prostatic venous plexus. We also investigated the disappearance of PAP from the circulation after total prostatectomy and staging pelvic lymphadenectomies in 5 patients with nonmetastazing prostatic cancer and in 1 patient with bladder cancer. During the postmaximum period, serum PAP concentrations declined, following 2-exponential curves, the 1st mean half life of elimination being 1.2 hours (range 0.5--2.5 hours). It is possible that PAP released from the prostate during the operation was eliminated during the 1st period. The 2nd half life was found to be remarkably long (mean = 281 hours), and it may represent PAP bound by serum protein(s).

Acid Phosphatase↗

Radioimmunoassayable prostate-specific acid phosphatase in peripheral and bone marrow sera compared in diagnosis of prostatic cancer patients.

Measurements of human prostate-specific acid phosphatase by radioimmunoassay in peripheral and bone marrow sera were compared. We studied 20 patients with benign prostatic hyperplasia, 27 with untreated prostatic cancer without bone metastases and 11 with metastases, in addition to 7 with cancer treated by hormonal therapy. The prostate-specific acid phosphatase concentrations in peripheral and bone marrow serum samples were equal and did not exceed the upper limit of our health-associated reference interval, 2.8 microgram. per 1. (mean plus 2 standard deviations) in patients with prostatic hyperplasia. Of 27 prostatic cancer patients without bone metastases the concentration of prostate-specific acid phosphatase was elevated in the peripheral sera of 20 and in the bone marrow sera of 21, and 21 had an extracapsular tumor (stage T3 to T4). Prostate-specific acid phosphatase concentrations were elevated in peripheral and bone marrow serum specimens of all 11 patients with metastases and bone marrow cytology studies were positive in 2. There was no difference in prostate-specific acid phosphatase concentrations in peripheral and bone marrow serum specimens from prostatic cancer patients undergoing hormonal treatment. We conclude that the use of bone marrow serum for the measurement of radioimmunoassayable prostate-specific acid phosphatase in prostatic cancer patients does not provide any further information in regard to the detection of prostatic cancer compared to the use of peripheral serum specimens. Falsely positive findings in bone marrow specimens were not observed with the method used.

Acid Phosphatase↗

The desmoid tumor. III. A biochemical and genetic analysis.

We have carefully examined four patients with desmoid tumor (DT) and their 31 relatives. In three of four cases, biopsies of the DT demonstrated low yet significant amounts of estrogen but not progesterone receptors in the tumor cytosol. In the fourth case, where the receptors were not demonstrable, the affected patient was a menopausal woman and the receptors may have been blocked by endogenous estrogen. Fourteen of their 31 relatives demonstrated multiple minor bone malformations in x-ray screening of the skeleton. The inheritance of these malformations was compatible with an autosomal dominant trait with variable penetrance. These findings are compatible with our suggestion that the basic underlying cause for DT is an inherited defect in growth regulation of the connective tissue. When a trauma is superimposed on such an individual, a DT may result. The growth of the tumor is, however, controlled primarily by sex hormones, estrogen predominance over progesterone being inducive to tumor growth.

Abnormalities, Multiple↗

HCG-stimulation of testicular steroidogenesis during induced hyper- and hypoprolactinaemia in man.

In order to elucidate the role of prolactin in the regulation of testicular steroidogenesis in man, hyper- and hypoprolactinaemia were induced by sulpiride (group 2) and bromocriptine (group 3) administration in eight and nine young adults, respectively, and the responses of testosterone and six other steroids to a single dose of 5000 iu hCG were compared with those obtained under basal conditions (group 1) in eight men. During hyperprolactinaemia (group 2) the responses of pregnenolone, progesterone, 17-hydroxyprogesterone, testosterone and 5 alpha-dihydrotestosterone tended to be greater than in the control and hypoprolactinaemia groups, but these changes were not statistically significant. In contrast to the behaviour of these steroids, oestradiol showed diminished peak values at 24-36 hCG in the sulpiride-treated group and the response was significantly smaller (P less than 0 . 01) than during hypoprolactinaemia. These findings suggest that testicular aromatization is modulated by prolactin and thus the partial inhibition of oestradiol production, observed during short-term hyperprolactinaemia, may result in a better androgen response to hCG.

Adult↗

Human testicular LH receptors: correlations with circulating gonadotrophins and testicular steroid secretion.

Testicular androgen production is regulated by circulating LH, the effect of which is mediated by its testicular membrane receptors. In the present study, testicular [125I]hCG binding in man was investigated and found to be characterized by saturability and high affinity (mean KD in testes of 21 patients with prostatic carcinoma = 1.64 X 10(-10) M), and stimulated testosterone production in dispersed interstitial cells in vitro. The concentrations of the LH receptors correlated with serum FSH concentrations (r = 0.52, P less than 0.05) but not with circulating LH levels. Neither had they any correlation with intratesticular testosterone, 5 alpha-dihydrotestosterone, androstenedione, progesterone, 17-hydroxyprogesterone or pregnenolone concentrations, which may be due to the fact that LH receptors are confined to Leydig cells, whereas steroids may be unevenly distributed in the different cells of the testis. In contrast, the concentrations of the LH receptor displayed positive correlations with the concentrations of testosterone (r = 0.81, P less than 0.001), androstenedione (r = 0.54, P less than 0.05), 17-hydroxyprogesterone (r = 0.76, P less than 0.001) and progesterone (r = 0.60, P less than 0.05) in the spermatic vein serum of the patients. Our data suggest that the Leydig cells mainly responsible for steroid secretion into the blood are under gonadotrophic control exerted via their receptors, whereas Leydig cell function is not rapidly reflected in steroid concentrations within the testis itself.

Aged↗

Subnormal pubertal increases of serum androgens in Turner's syndrome.

60 patients (139 blood specimens) with Turner's syndrome were investigated in order to obtain information concerning the origin of the increments of androgens during puberty. The concentrations of serum FSH, LH, estradiol, testosterone, 5 alpha-dihydrotestosterone, dehydroepiandrosterone, progesterone, 17-hydroxyprogesterone and pregnenolone in patients less than 10 years old were identical to those previously found in normal healthy girls of the same age. Hence, in adrenarche the early increase of androgen secretion is independent of gonadal hormone secretion. The later increases in serum testosterone and androstenedione in our patients were very small, and the age of 15 years, their concentrations were 50 and 60%, respectively, of the corresponding levels in normal girls of the same age. After 13 years of age, the mean serum dehydroepiandrosterone concentration was also slightly, but significantly (20-30%), lower than in normal girls of the same age. It is concluded that the ovaries are responsible for most of the pubertal rises in circulating testosterone and androstenedione, and possibly for a small part of the late pubertal rise in dehydroepiandrosterone.

Adolescent↗

Screening of bacteria in urine using luciferin-luciferase assay of microbial ATP: a comparative study.

A total of 3227 urine specimens were analysed to investigate the applicability of a firefly luciferase assay of microbial adenosine triphosphate (ATP) for the rapid screening of bacteriuria in clinical specimens. Urine sediment, dipslide culture, and three plate cultures were also investigated in the majority of the urine specimens, the plate cultures serving as the reference. Of the specimens with positive plate culture (greater than or equal to 10(5) colony forming units (CFU)), leucocyte content of the spun urine sediment was negative (less than or equal to 4 cells per high-power field) in 34% and bacterial content was negative in 14% (no bacteria seen microscopically); the dipslide test was negative (less than 10(5) CFU) in 16%, and the luminescence assay of ATP in 7% (less than or equal to 500 relative light units). Of the urine specimens forming less than 10(5) CFU on plate cultures, leucocytes were positive in 15%, spun sediment bacteria in 21%, the dipslide test in 0.5%, and the luminescence assay of ATP in 11%. When used as a screening test for further studies by complete culture techniques, the luminescence assay of microbial ATP can improve the rapid diagnosis of urinary tract infections.

Adenosine Triphosphate↗