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Biomedical subjects

R Vihko

Publications and source records attributed to R Vihko.

At least 217 records · Page 12Linked to original sources

Serum steroids in normal males and patients with prostatic diseases.

The subjects investigated comprised 57 normal males between 30 and 80 years of age; 40 patients between 50 and 80 years of age suffering from benign prostatic hypertrophy (BPH), and 11 untreated prostatic carcinoma (Ca) patients aged between 57 and 79 years. Serum concentrations of oestradiol, pregnenolone, progesterone, 17alpha-hydroxyprogesterone, androstenedione, testosterone, 5alpha-dihydrotestosterone and androsterone were determined from a single serum sample (1.6 ml). Oestradiol was determined by an automated non-chromatographic radioimmunoassay, while other steroids were determined by radioimmunoassays, after solvent extraction and chromatographic purification on Lipidex-5000TM microcolumns. When patient groups were compared with the 25 normal males between 50 and 80 years of age, several conclusions could be drawn. Serum concentrations of 5alpha-dihydrotestosterone (P less than 0.01) and 17alpha-hydroxyprogesterone (P less than 0.001) were both significantly higher in the BPH patients when compared with the normal males. This trend was also apparent in the serum concentrations of progesterone and testosterone in the older BPH patients. Although the mean concentrations of 5alpha-dihydrotestosterone and 17alpha-hydroxyprogesterone were slightly higher in carcinoma patients than normal males, these differences were not statistically significant. No differences were seen in the concentrations of pregnenolone, androstenedione, androsterone and oestradiol between normal subjects and patients with BPH or prostatic Ca.

Adult↗

Ultrastructural and steroidogenic characteristics of an androgen-producing adrenocortical tumour.

A 16-year-old female patient with an adrenal tumour was studied. Clinically she had progressive hirsutism, showed high urinary 17-oxosteroid excretion with normal plasma cortisol. Plasma C19-steroids, both unconjugated (including testosterone) and sulphate-conjugated, were greatly elevated. On surgical exploration an adrenal tumour was histologically an adenoma. On ultrastructural analysis the cells in all zones of the adjoining adrenal were considered normal. Although the tumour cells had the general appearance of a steroid-secreting cell their structure diverged from the cells of every subzone of the cortex. This was the case particularly with mitochondria and lipid inclusions. The only endogenous unconjugated steroids detected in the adjoining cortex were corticosterone and cortisol while in tumour tissue these were present in lesser amounts. The tumour tissue contained large amounts of C19-steroids, 11beta-hydroxy-androstenedione being quantitatively most significant. On the basis of the steroid profile an impaired defect of 21-hydroxylation in tumour cells leading steroid synthesis from corticosteroidogenesis to the C19 pathway is proposed.

Adenoma↗

Serum prolactin, FSH and LH during puberty in girls and boys.

Serum prolactin, follicle-stimulating hormone and luteinizing hormone were determined in 200 girls and 80 boys. The boys have been examined on three occasions at one-year intervals and the girls twice at 1.5-year intervals. In girls, serum FSH rapidly increased in the youngest age groups (7.5-11.5 years), whereas in boys, the increase took place later and the first significant increase was seen between age groups 9.5 and 12.5 years. In girls, a rise in serum LH took place later than that of FSH (between 10.5 and 11.5 years), and LH peaked at 13.0-13.5 years. In boys, the timing in the changes of serum LH closely resembled that of FSH. The girls displayed a significant increase in serum prolactin between 7.5 and 8.5 years, and this was followed by a slow progressive increase. In the group of boys, serum prolactin did not show any significant changes. In girls, there was a correlation between serum LH and body weight, as well as calculated fat amount and body fat percentage early in puberty. There was no correlation between serum LH and chronological or bone age in this age group, which suggests that the correlation found is not due to age-related parallel phenomena.

Adolescent↗

Hormonal pattern of adolescent menstrual cycles.

Serum FSH, LH, PRL, estradiol, pregnenolone, progesterone, 17-hydroxyprogesterone, androstenedione, testosterone, 5 alpha-dihydrotestosterone, and androsterone were measured radioimmunologically in 20 normal girls aged 13-17 yr. Samples were taken every day or every second day during one menstrual cycle. The cycles recorded could be divided into three groups. The first and oldest group consisted of 10 girls with a mean gynecological age (years since menarche) of 2.9 yr. The luteal phase was at least 11 days and the progesterone concentration was at least 5 ng/ml. The testosterone rise (mean, 55%) on the day of LH surge correlated well with the simultaneous progesterone rise (mean, 270%) and the following luteal progesterone secretion. A negative correlation was seen between the FSH concentration on days 3-4 of the cycle and the length of the follicular phase. The second group consisted of 4 girls who had a mean gynecological age of 1.5 yr. The luteal phase was of 4- to 8-day duration and the progesterone secretion was lower than in group I. The follicular phase testosterone concentration was lower in group II as compared to group I. No "periovulatory" testosterone increases were seen, although every cycle displayed an LH and FSH peak. The third group consisted of 6 girls with a mean gynecological age of 1.1 yr. These cycles were anovulatory, as the serum progesterone concentration never exceeded 1.0 ng/ml. In two cycles, signs of follicular maturation were seen. In the four others, the androgen levels tended to be elevated. In two cases, the testosterone and androstenedione concentrations were 2-4 times elevated from the beginning of these two cycles. Thus, the hormonal pattern of adolescent menstrual cycles is far from uniform. It is very likely that in addition to gonadotropins, estradiol and progesterone, androgens may also have a role in the development and maintenance of normal menstrual function in the female.

Adolescent↗

Serum prostate-specific acid phosphatase: development and validation of a specific radioimmunoassay.

We describe radioimmunoassay for human prostatic acid phosphatase [orthophosphoric-monoester phospho-hydrolase (acid optimum), EC 3.1.3.2] in serum, with use of monospecific antisera raised in rabbits against highly purified acid phosphatase from human prostates. The antiserum did not cross react with partly purified acid phosphatases from human spleen, erythrocytes, or synovial tissues. 125I-labeled acid phosphatase was prepared by a Chloramine T method, and the bound and free antigen was separated in the assay by use of anti-rabbit gamma-globulin raised in sheep. Uniform low nonspecific binding of the [125I]acid phosphatase was achieved by using acid-phosphatase-free serum to prepare standard curves and diluted samples of serum with high acid phosphatase activities. Concentrations of immunoreactive acid phosphatase in the serum of healthy men ranged from less than 1 to 10 microgram/liter and for 12 patients with advanced prostatic carcinoma between 100 and 500 microgram/liter. The concentrations of the enzyme in sera of patients with benign prostatic hyperplasia were very similar to those in sera of the reference group.

Acid Phosphatase↗

Serum FSH, LH and prolactin in normal males and patients with prostatic diseases.

Serum FSH, LH and prolactin were measured in fifty-eight normal males between 30 and 80 years of age. At the same time similar estimations were performed on samples taken from 232 patients with benign prostatic hypertrophy (BPH) and twenty-six patients with prostatic carcinoma. The three groups were compared with respect to age, and it was observed that significant rises related to age occurred in the serum levels of FSH, LH and prolactin in normal men after the sixth decade. The patient groups did not differ significantly from each other, or from the normal age-matched population in respect to prolactin and FSH levels. Serum LH in both the carcinoma and BPH patient groups, however, differed significantly from the controls, and remained at the level associated with younger normal males. It is suggested that testosterone metabolites from the prostate exert a negative feedback on pituitary LH secretion.

Adult↗

The simultaneous radioimmunoassay of seven steroids in human spermatic and peripheral venous blood.

Seven unconjugated neutral steroids, including testosterone and some of its precursors and metabolites, were measured in the peripheral and spermatic venous blood males, employing specific radioimmunoassays after the fractionation of steroids on Lipidex-5000 (hydroxyalkoxypropyl Sephadex) microcolumns. Respective mean concentrations (ng/ml) and ranges of steroids estimated in peripheral and spermatic venous blood in all groups of patients were as follows: pregnenolone, 0.71 (0.29-2.39) and 10.97 (0.83-30.1); progesterone, 0.31 (0.02-0.57) and 10.17 (1.51-33.24); 17 alpha-hydroxyprogesterone, 1.04 (0.48-2.20) and 37.33 (1.68-141.00); androstenedione, 1.01 (0.26-2.65) and 11.87 (0.97-30.18); testosterone, 3.84 (0.63-10.64) and 255.1 (2.85-619.1); 5alpha-dihydrotestosterone, 0.19 (0.07-0.28) and 3.74 (0.04-9.71); androsterone, 0.27 (0.12-0.47) and 0.97 (0.20-2.15). Concentrations are similar to those estimated by mass spectrometry and protein binding assays, except for androsterone which has not previously been measured in this context. The low, but significant testicular secretion of both 5alpha-hydrotestosterone and androsterone suggests that these two steroids are testicular androgen metabolites, and that androgen metabolism in this tissue may be monitored by way of their measurement in spermatic vein blood.

Adult↗

Automation of radioimmunoassays for some sex steroids with use of both iodinated and tritiated ligands.

We describe an automated technique for estradiol, progesterone, and testosterone, in which System Olli 3000 pipetting and incubation units are used. After extraction or chromatography, steroids are redissolved in ethanol or buffer, and duplicate aliquots are arranged for radioimmunoassay in 24-tube blocks. Addition of antibodies, tracers (125I or 3H), dextran-coated charcoal for separating free and bound ligands, and removal of a portion of the supernate for counting are all performed by the pipetting instrument. Incubations are at 37 degrees C in the incubation unit, or at 4 degrees C. After counting, steroid concentrations are computed from punch tape records by a Nova 840 computer. The management of assays in 24-tube units, and accurate simultaneous pipetting has reduced experimental error, and because there is no carryover, many different assays can be performed concurrently or in rapid sequence. Various scintillation media are compared.

Antibody Specificity↗

Biological effects of a new and potent progestagen. A clinical study.

The biological effects of a new synthetic progestagen, Org 2969 (13-ethyl-11-methylene-18,19-dinor-17 alpha-pregn-4-en-20-yn-17-ol) were studied in healthy normally menstruating women. Two of them were given 0.125 mg, five 0.060 mg and two 0.030 mg of Org 2969 daily on days 1-20 during one menstrual cycle. Serum levels of follicle stimulating hormone, luteinizing hormone, progesterone and oestradiol were analyzed on days 8-23 in order to evaluate the function of the hypophyseal-ovarian axis. The serum concentrations of aspartate amino transferase, alanine amino transferase, alkaline phosphatase, gamma glutamyl transpeptidase and bilirubin were determined to evaluate possible side effects on live function on days 8, 15 and 23. Serum cortisol was measured on days 8 and 23. The basal body temperature was recorded daily during the whole cycle, and endometrium biopsies were taken on days 21 or 22 of the cycle. All samples were taken similaryl during the treatment cycle and the preceding control cycle. According to the hormone determinations, all the treatment cycles were anovulatory except in one woman receiving the lowest dose. The treatment led to decreased spinnbarkeit, arborization and sperum penetration in the cervical mucus. Liver function tests and serum cortisol remained unchanged during the treatment.

Administration, Oral↗

Simultaneous determination of five sex hormones in human serum by radioimmunoassay after chromatography on Lipidex-5000.

We describe a method for determination of pregnenolone, progesterone, 17alpha-hydroxyprogesterone, testosterone, and 5alpha-dihydrotestosterone in 1-2 ml of serum from male or female. Using microcolumns of Lipidex-5000 (hydroxyalkoxypropyl Sephadex, 0.5 g) and light petroleum/chloroform (97/3) as the solvent during chromatography, we resolved these five steroids into four fractions, with pregnenolone and 5alpha-dihydrotestosterone eluting together. By use of selected antibodies, the latter two steroids were also determined specifically. Use of microcolumns allowed minimization of solvent volumes and sample transfers. Consequently, blank values for all the five steroids were negligible. Lowest measureable concentrations (in ng/liter) were: pregnenolone 100, progesterone 25, 17alpha-hydroxyprogesterone 50, testosterone 25, and 5alpha-dihydrotestosterone 25. Intra-assay and inter-assay coefficients of variation ranged from 5 to 9% and 10 to 15%, respectively, for the five steroids. Serum concentrations of these steroids are given for women in the follicular and luteal phases of the menstrual cycle and for women on oral contraceptives of the combination type, as well as for normal men.

Antibody Specificity↗

Lipidex chromatography in the radioimmunoassay of serum and urinary cortisol.

A highly specific method for the determination of cortisol in human serum and urine is described. The sample is first extracted with diethyl ether/ethyl acetate (1 : 1, by vol.), then chromatographed on a highly lipophilic derivative of Sephadex (hydroxyalkoxypropyl Sephadex, Lipidex) in light petroleum/chloroform (1 : 1, by vol.), and finally cortisol is measured by radioimmunoassay using a cortisol-21-BSA antiserum. Bound and unbound radioactivities are separated using dextran-coated charcoal technique. The 8 a.m. values (mean +/- S.D.) of cortisol among 11 young females and 16 young males were 152 +/- 32 ng/ml (range 111-235) and 185 +/- 21 ng/ml (103-232), respectively. The respective values at 4 p.m. were 84 +/- 29 ng/ml (26-117) and 84 +/- 36 ng/ml (32-172). The importance of Lipidex chromatography was demonstrated with assays of serum samples from children with congenital adrenal hyperplasia; without chromatography cortisol values were 6 times those with chromatography. Specific cortisol assays from pregnancy serum also necessitated Lipidex chromatography. Among 11 young men and 9 young women the mean daily urinary cortisol excretion was 56 +/- 26 mug (32-109) and 60 +/- 24 mug (39-109), respectively. Specific urinary cortisol determination could not be achieved without Lipidex chromatography.

Adrenal Glands↗