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Biomedical subjects

R Vihko

Publications and source records attributed to R Vihko.

At least 91 records · Page 5Linked to original sources
PubMed1987

Metoclopramide-induced hyperprolactinaemia: effects on corpus luteum function, endometrial steroid receptor concentrations and 17 beta-hydroxysteroid dehydrogenase activity.

Induced hyperprolactinaemia impairs ovarian follicular development, especially during the recruitment period. The consequences of hyperprolactinaemia during the luteal phase alone on corpus luteum function have not been characterized, nor have the actions of excessive circulating PRL on the endometrium. In this study, postovulatory 5-d administration of metoclopramide (MC) increased serum concentrations of PRL and decreased those of pregnenolone and progesterone indicating inhibition of steroidogenesis in the corpus luteum. This effect may partly explain the relatively common failure of implantation in association with induced ovulation using regimens leading to transient hyperprolactinaemia. In contrast to this, MC-induced hyperprolactinaemia during the mid-follicular (4 d) or early luteal phase of the cycle did not alter the concentrations of cytosol or nuclear oestrogen and progestin receptors or the activity of 17 beta-hydroxysteroid dehydrogenase in endometrial tissue. Thus, transiently elevated circulating PRL does not seem to have direct effects on female sex steroid receptors or their function in the proliferative or secretory endometrium.

17-Hydroxysteroid Dehydrogenases↗
PubMed1987

Evidence for an androgen receptor in porcine Leydig cells.

Cytosol and nuclear androgen receptor concentrations were measured in freshly prepared and cultured Leydig cells of immature pig testis with exchange assays using [3H]methyltrienolone as labelled ligand. Androgen receptors in Leydig cells had high affinity for [3H]methyltrienolone and steroid binding specificity typical of an androgen receptor. The mean receptor concentrations were 76 fmol/mg protein and 210 fmol/mg DNA for cytosol and nuclei, respectively. In sucrose gradients, cytosol androgen receptors sedimented in the 4 S region. The cells maintained androgen receptors under culture conditions. Exposure of cultured cells to [3H]methyltrienolone (10 nmol/l) resulted in accumulation of androgen receptors in the nuclei with maximal uptake by 1 h. We conclude that methyltrienolone binding sites with characteristics of androgen receptors were identified in both cytosol and nuclei of porcine Leydig cells.

Animals↗
PubMed1987

High-affinity monoclonal antibodies specific for human prostatic acid phosphatase.

We produced two monoclonal hybridoma cell lines that secrete IgG immunoglobulins with high affinities (Kd = 7.3 to 8.0 X 10(-11) mol/L, Ka = 1.25 to 1.37 X 10(10) L/mol) for 125I-labeled human prostatic acid phosphatase (PAP), and that specifically bind this enzyme from human serum. The antibodies were produced in high titers in murine ascitic fluid (700 mg/L) and in cell-culture media (30 mg/L) and were further purified to homogeneity by affinity chromatography on PAP- and Protein A-Sepharose CL-4B. After purification they were shown to be homogeneous by liquid chromatography. Both of these monoclonal antibodies exhibit strict specificity for PAP as determined by radioimmunoassay and by immunofluorescence studies of human pancreas, kidney, prostate, and leukocytes. The antibodies react only with the native form of the enzyme, as shown by the slot-immunoblotting method.

Acid Phosphatase↗
PubMed1986

Acid phosphatases bind to the main high density lipoprotein apolipoprotein A-I.

The serum protein binding secretory prostatic acid phosphatase (PAP) and lysosomal placental acid phosphatase (LAP) was purified using affinity chromatography on gels containing immobilized acid phosphatases. The protein, which could be eluted from these enzyme affinity gels only with 0.05 mol/l HCl (pH 2.0), was shown to be apolipoprotein A-I (apo A-I), the main structural protein of high density lipoprotein (HDL).

Acid Phosphatase↗
PubMed1986

Concentrations of androgens in human benign prostatic hypertrophic tissues incubated for up to three days.

Twenty-one samples of surgically removed benign prostatic hypertrophy (BPH) were brought to the laboratory either in an insulated container (ambient temperature) or on ice. They were cleaned and roughly minced at room temperature. In 18 cases, samples of up to 1 g were kept at various temperatures (4 degrees C, c. 20 degrees C, and 37 degrees C) for up to 77 h; some were taken for storage (-70 degrees C) at the beginning and others at various times within this period. In three cases, portions of tissue were incubated in liquid medium in the absence and presence of testosterone. The concentrations of six androgens (testosterone, 5 alpha-dihydrotestosterone (5 alpha-DHT), 5 alpha-androstane-3 alpha, 17 beta-diol, androstenedione, 5 alpha-androstanedione, and androsterone) were measured by radioimmunoassays. The results indicated that in conditions resembling those after death, the BPH tissue content of 5 alpha-DHT falls to a variable degree, while concentrations of 5 alpha-androstane-3 alpha, 17 beta-diol, 5 alpha-androstanedione, and androsterone increase. After 2 to 3 days, the 5 alpha-DHT concentrations remained greater than those reported previously from this laboratory (and others) in normal prostate tissue removed at autopsy.

Aged↗
PubMed1986

The predictive value of steroid hormone receptor analysis in breast, endometrial and ovarian cancer.

The predictive value of female sex steroid, estrogen and progesterone, receptor (ER and PR, respectively) assays in breast, endometrial and ovarian cancer is reviewed with emphasis on comparative aspects of these malignant tumors in relation to their hormone dependency. The endocrine etiology of these three tumor types seems to be at least partly different, and so is the expression of these receptors in normal and malignant tissues of the breast, endometrium and ovary. There is a tendency for decreased receptor concentrations and disappearance of these receptors in association with advancement of these malignancies. There is also a decrease in the presence and concentrations of ER and PR in relation to loss of differentiation in breast and endometrial cancer. Receptor analyses have an established position in the selection of patients with advanced breast cancer for endocrine treatment, and they give promise of a similar application in endometrial cancer and in endometrioid cancer of the ovary. It is not clear whether the disease-free interval is related to the presence or concentrations of ER or PR as such in the tumor tissue. There is better survival in breast cancer patients with receptor-positive tumors, which might be due to a response to endocrine treatment. The same seems to be true for patients with endometrial cancer. Future progress in the application of female sex steroid receptor analyses in breast, endometrial and ovarian cancer needs additional controlled clinical trials and more highly developed receptor assays.

Breast Neoplasms↗
PubMed1986

Testicular responsiveness to human chorionic gonadotrophin during transient hypogonadotrophic hypogonadism induced by androgenic/anabolic steroids in power athletes.

Serum concentrations of testosterone, 17-hydroxyprogesterone, estradiol and several other unconjugated and sulphated steroids were analyzed before and after a single dose of hCG in 6 power athletes, who had used high doses of testosterone and anabolic steroids for 3 months. The study was carried out 3 weeks after cessation of drug use, but the study subjects were still characterized by hypogonadotrophic hypogonadism. The mean concentrations of serum LH and FSH were 2.6 +/- 0.3 and 1.1 +/- 0.03 mIU/ml (mean +/- SEM), respectively, and the concentrations of several precursors and metabolites of testosterone were lower than those before drug use. In contrast, circulating concentrations of steroid sulphates were not decreased, with the exception of dehydroepiandrosterone sulphate. After hCG injection serum testosterone and 5 alpha-dihydrotestosterone concentrations increased significantly, whereas no increases in estradiol and 17-hydroxyprogesterone concentrations were observed. These results demonstrate that during transient hypogonadotrophism in adult men, the testicular responsiveness to a single injection of hCG is similar to that in prepubertal boys without any sign of steroidogenic lesion at the 17,20-desmolase step. Therefore, the appearance of the possibly estradiol-mediated inhibition at the level of C21-steroid side-chain splitting in testosterone biosynthesis seems to be dependent on priming by gonadotrophins.

Adult↗
PubMed1986

Regulation of serum testosterone in men with steroid sulfatase deficiency: response to human chorionic gonadotropin.

Human chorionic gonadotropin (hCG; 5000 IU) was administered to 6 control men and 6 patients with recessive x-linked ichthyosis (RXLI) with verified 3 beta-hydroxysteroid sulfate sulfatase (3 beta-HSS) deficiency in their skin biopsy samples. Concentrations of steroids and their sulfate conjugates were determined in peripheral serum specimens collected a day before and 4 days after hCG administration. Testosterone concentrations were identical in patients and controls. Baseline serum LH concentrations were also identical in the 2 groups showing that there were no major differences in the regulation of the hypothalamic-pituitary-gonadal axis. The significantly increased (31-82%) serum concentrations of sulfated pregnenolone, 17-hydroxypregnenolone, dehydroepiandrosterone and 5-androstene-3 beta,17 beta-diol in patients compared with controls indicated that their circulating concentrations were regulated by 3 beta-HSS. This is in line with the fact that the baseline concentrations of the same unconjugated steroids were significantly lower (32-90%) in patients with RXLI, suggesting that a proportion of these circulating steroids were derived from the corresponding sulfated precursors. The response patterns and actual concentrations of testosterone, 17-hydroxyprogesterone and estradiol were similar in the patients and the controls after hCG. The decreased concentrations of testosterone sulfated at carbon 17 under baseline conditions and after hCG in patients with RXLI remains enigmatic. In conclusion, testosterone production and the response to hCG seem to be identical in patients with RXLI and controls despite the fact that significant differences were observed in the circulating concentrations of several unconjugated and sulfated testosterone precursors.

Adult↗
PubMed1985

Significance of estrogen and progesterone receptors, disease-free interval, and site of first metastasis on survival of breast cancer patients.

Estrogen and progesterone receptors (ER/PR) were measured in primary tumors and metastases of 397 breast cancer patients. Survival following mastectomy was significantly longer in patients with ER and PR positive tumors, as was survival after first recurrence. The prognostic value of ER and PR was compared with such clinical factors as disease-free interval (DFI) and the dominant site of first metastasis by Cox's regression analysis. With all the different therapy modalities long DFI was the best prognostic indicator. However, in the patient group treated with endocrine therapy, ER and PR positivity was the best prognostic indicator, suggesting that longer survival in receptor positive patients was related to the response to endocrine treatment.

Breast Neoplasms↗
PubMed1985

Screening for carcinoma of the prostate. Rectal examination, and enzymatic and radioimmunologic measurements of serum acid phosphatase compared.

Veterans (n = 771, 54-76 years of age) from the Second World War, who attended a rehabilitation program arranged by the state between the years 1979 and 1983, were screened for prostatic cancer by rectal examination of the prostate and by measurement of serum prostate-specific acid phosphatase (PAP) concentration and enzyme activity (total and tartrate-labile). Nine cases with prostatic cancer confirmed by needle biopsy were found. Serum PAP concentrations were elevated in five of the nine cancer patients and rectal examination was positive in six of them, whereas the serum PAP concentration was elevated and rectal examination was positive simultaneously only in two patients. Serum PAP concentrations were elevated in 25 patients without prostatic cancer, and rectal palpation of the prostate resulted in 21 false-positive findings. The enzyme activity of serum acid phosphatase was not elevated in any of the nine patients diagnosed as having prostatic cancer. The predictive value of a positive finding in serum PAP concentration (16.7%) or rectal palpation of the prostate (22.2%) in this unselected, asymptomatic population was similar and low. Both tests together gave additive information.

Acid Phosphatase↗
PubMed1985

Human leukocyte interferon inhibits human chorionic gonadotropin stimulated testosterone production by porcine Leydig cells in culture.

Pretreatment of primary porcine Leydig cell cultures with human leukocyte interferon suppressed the subsequent hCG-stimulated testosterone production in a dose-dependent manner, with an ED50 at 13 IU/ml. The treatment had no effect on hCG-binding to its receptor, and the inhibition of testosterone production was not abolished by 8Br-cAMP addition. The results indicate that the site of interferon action on hCG-stimulated testosterone production in primary cultures of porcine Leydig cells is located distal to cAMP formation.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1985

Short-term effects of danazol and medroxyprogesterone acetate on cytosol and nuclear estrogen and progestin receptors, 17 beta-hydroxysteroid dehydrogenase activity, histopathology, and ultrastructure of human endometrial adenocarcinoma.

We measured concentrations of cytosol and nuclear estrogen, as well as progestin receptors and activities of 17 beta-hydroxysteroid dehydrogenase (17-HSD), and examined histopathology and ultrastructure of endometrial carcinoma specimens taken before and after one-week danazol (200 mg, 3 times daily) or medroxyprogesterone acetate (MPA, 100 mg daily) treatments in 14 and 16 patients, respectively. A typical progestin effect, a significant increase in the activity of 17-HSD, was observed after both treatments. The post-therapy 17-HSD activities correlated significantly with the pretreatment cytosol progestin receptor concentrations in both treatment groups. Both MPA and danazol decreased the proliferative activity and increased the secretory activity of the malignant epithelial endometrial cells. These biochemical and morphological results support the concept that danazol has progestin-like actions on the human endometrium, and might therefore be an alternative for hormonal treatment of endometrial carcinoma.

17-Hydroxysteroid Dehydrogenases↗
PubMed1985

Effects of long-term administration of tamoxifen on steroid metabolism in prostatic carcinoma patients.

Six patients with advanced prostatic carcinoma were treated with tamoxifen (2 X 20 mg daily) for up to 3 months before orchiectomy. Blood samples for gonadotropin, sex steroid, and prostate-specific acid phosphatase (PAP) determinations were taken before tamoxifen treatment, daily for 1 week, and at monthly intervals. Steroid concentrations in the testis tissue and spermatic vein blood were assayed from samples taken at orchiectomy. No consistent changes were observed during tamoxifen treatment, although there was a transient drop in the mean concentrations of LH on days 3 and 4 of treatment. The circulating concentrations of estradiol tended to be increased at 1, 2, and 3 months of treatment. The spermatic vein concentrations of testosterone and its precursors tended to be higher than those in nontreated prostatic carcinoma patients previously reported from this laboratory, indicating slight stimulation of testicular steroidogenesis. There were no changes in circulating levels of PAP and no improvement in clinical condition, indicating that long-term tamoxifen administration is not effective in the treatment of prostate carcinoma.

Aged↗
PubMed1985

Testicular responsiveness to hCG before and after long-term antiestrogen treatment in oligozoospermic men.

In order to further investigate the role of endogenous estradiol in the regulation of testicular steroidogenesis an hCG-stimulation test (a single dose of 5000 i.u. i.m.) was performed in 5 normogonadotropic oligozoospermic men before and after 3 months of antiestrogen (clomiphene citrate = CC) treatment (50 mg p.o. daily). Peripheral blood samples were collected immediately before hCG administration and thereafter at 1, 4 and 7 days, and were analyzed for testosterone (T), estradiol (E2), 17-hydroxyprogesterone (17-OHP4), 17-hydroxypregnenolone (17-OHP5), 11 other free and sulfate-conjugated steroids, and for sex hormone-binding globulin (SHBG). The results demonstrated that CC-treatment caused a significant rise in peripheral serum concentrations of SHBG, T, 5 alpha-dihydrotestosterone (DHT), E2 and the sulfate conjugates of pregnenolone, 17-OHP5, 5-androstene-3 beta, 17 beta-diol and T. In the basal state, before the CC-treatment, apparently normal responses to hCG were seen in unconjugated steroids: 17-OHP4 and E2 concentrations were significantly elevated at 1 day, and those of T at 4 days. After CC, only the concentrations of 17-OHP4 rose significantly following hCG administration. The peripheral serum concentrations of the 5-ene- and sulfate-conjugated precursors of T were not influenced by hCG in the basal state or after CC. These results suggest that the apparently E2-mediated inhibition of 17,20-lyase activity in the 4-ene-pathway of T synthesis could not be totally prevented by long-term antiestrogen treatment, and that in the 5-ene-pathway no sign of 17,20-lyase inhibition was demonstrated either before or following CC-treatment. The significant rise in the circulating concentrations of sulfate-conjugated steroids following long-term CC administration, apparently due to increased synthesis of T and its precursors in the 5-ene-pathway, strengthens the concept of their importance in testicular steroidogenesis.

Adult↗
PubMed1985

Relationships between unconjugated and sulphated steroids in porcine primary Leydig cell culture.

Steroidogenesis in immature porcine Leydig cells was investigated in primary culture at 48-84 h under basal conditions and in the presence of hCG. The basal accumulation of unconjugated steroids was close to linear only during the first 4 h of study, whereas the sulphate-conjugated steroids accumulated essentially linearly over the 36 h experimental period. At the last time point, 95% of the steroids measured were sulphated. Stimulation with hCG (1 ng/ml) led to a still more pronounced sulphate conjugation, and approx 99% of the steroids measured were sulphated at 36 h. Under maximal stimulation with hCG (100 ng/ml) the sulphates accounted for 74% of the total steroids measured at 36 h. Testosterone, androstenedione, dehydroepiandrosterone, 5-androstene-3 beta, 17 beta-diol and estrone were usually quantitatively the most important unconjugated steroids, and sulphated dehydroepiandrosterone, estrone, testosterone and 5-androstene-3 beta, 17 beta-diol were the most important steroid sulphates, especially following maximal stimulation of the cultures. These data emphasize the importance of steroid sulphates in porcine testicular steroid metabolism. Under stimulation with hCG, there was a rapid response in testicular steroidogenesis, initially seen as a rapid increase in the secretion of unconjugated and sulphated steroids. At approx 4-12 h, the rate of sulphate conjugation appeared to reach or even to exceed that of steroid biosynthesis, which lead to stabilisation or a decrease in the concentrations of unconjugated steroids. Only high doses of hCG, 10-100 ng/ml, were then able to lead to a net accumulation of unconjugated steroids, at 24-36 h of incubation with hCG.

Animals↗