Effect of gonadotropin-releasing hormone on pituitary-gonadal function of male infants during the first year of life.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to R Vihko.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The administration of danazol, 200 mg three times daily, from the 3rd to the 23rd day of the cycle to normally menstruating women exhibited the following actions on the human endometrium: significantly reduced cytosol oestrogen and progestin receptor concentrations, and declined 17 beta-hydroxysteroid dehydrogenase activity. Very similar results were obtained during medroxyprogesterone acetate (100 mg daily) treatment for the same period of time. Danazol administration did not decrease circulating gonadotrophin levels but clearly suppressed luteal serum oestradiol and progesterone concentrations. Danazol was found to bind in vitro to endometrial progestin receptor with an affinity approximately 3% of that of progesterone. These findings are compatible with the notion that a local progestin-like rather than a systemic action of danazol is the way by which its therapeutic effect is exerted. This may be potentiated by the suppression of circulating oestradiol levels.
We describe a semiautomated batch-assay system designed to increase the speed and ease of performing radioimmunoassays while maintaining good accuracy and precision. The main components are a programmable pipetting unit (sample processor) and a gamma counter capable of simultaneously counting radioactivity in 12 samples. The processor uses prearranged sets of as many as 24 disposable pipette tips, which eliminates carryover between samples, and features a horizontal shaker and magnetic stirrer; 50 different assay protocols can be selected. Batches of tubes are easily transferred from the sample processor to the incubator and centrifuge. The gamma counter is controlled by a microprocessor, which is also used for data processing. Because the system is based on discrete rather than continuous-flow analysis and because of the ease with which consecutive samples can be processed, more than one operation and several different assays can be accommodated simultaneously, which saves time considerably.
Cytosol estrogen (ER) and progestin (PR) receptors were quantified in 47 endometriosis lesions from 41 patients and compared with receptor measurements in the endometrial tissue of nine of these patients. Half of the specimens of endometriosis tissue contained PR only, in concentrations that were significantly lower than in the endometrium. Only 30% of the specimens of endometriosis tissue contained the two receptors simultaneously, and levels of ER were very low compared with those in the endometrium. Levels of PR in the specimens of endometriosis tissue were highest at the periovulatory period, whereas concentrations of ER tended to be highest at the beginning and close to the end of the cycle. These results suggest that regulation of these receptors is dissimilar in endometriosis lesions and endometrium. It remains to be seen whether differences in receptor distribution in the lesions of individual patients could explain differences in the course of this disease, and have therapeutic implications. The presence of PR in the majority of the endometriosis lesions is in accord with the favorable therapeutic response often obtained with progestin treatment of this disease.
To inhibit endometrial stimulation during postmenopausal estrogen therapy, 25 women with climacteric symptoms were treated with a daily dose of 1.25 mg of conjugated estrogens for 7 weeks followed by a period of 10 days with clomiphene citrate administration (50 mg per day). This combination was repeated three times during the 6-month trial. The marked relief of climacteric symptoms with estrogen was slightly less during clomiphene treatment. Uterine bleeding occurred five times during estrogen treatment periods but never during or after clomiphene supplementation. Histologic examination revealed endometrial atrophy in 41% of the samples after the first estrogen treatment, whereas after the first and third clomiphene periods this was increased to 77% and 73%, respectively. The first clomiphene treatment significantly decreased the concentrations of cytosol estrogen and progestin receptors in endometrium, as compared with the levels recorded at the end of the preceding estrogen therapy. The depression in the cytosol estrogen receptor concentration was persistent, whereas cytosol progestin receptor concentration tended to increase during the subsequent estrogen-plus-clomiphene treatment. Estrogen declined serum concentration of follicle-stimulating hormone (FSH), whereas the concentration of luteinizing hormone (LH) and prolactin remained unchanged. Clomiphene did not change the levels of these hormones from those observed during the estrogen treatment. The concentration of free fatty acids in serum was increased during the estrogen and clomiphene treatments, whereas the levels of cholesterol and high-density lipoprotein--cholesterol did not change. Our results suggest that this treatment regimen relieves climacteric symptoms without endometrial stimulation or other adverse effects. Thus, clomiphene appears to be a practical alternative to progestin for interruption of the postmenopausal endometrial effect of estrogen.
The concentrations of prostate-specific acid phosphatase (PAP), testosterone, 5 alpha-dihydrotestosterone (5 alpha-DHT), 5 alpha-androstane-3 alpha, 17 beta-diol, androstenedione, 5 alpha-androstanedione, and androsterone were measured by specific radioimmunoassays in whole pieces and in separated epithelium from human benign prostatic hypertrophic (BPH) tissues. Significant correlations were noted between the concentrations of PAP and 5 alpha-DHT, and PAP and 5 alpha-androstane-3 alpha, 17 beta-diol in the epithelium, and between PAP and androstenedione, and PAP and testosterone PAP is androgen dependent, particularly as regards 5 alpha-DHT, whereas 5 alpha-androstane-3 alpha, 17 beta-diol may operate after conversion to 5 alpha-DHT. There is no obvious explanation for the correlations noted in whole tissue, but is suggested that circulating androgens, representing the androgen source for the prostate, primarily determine the production of PAP. The majority of the PAP in BPH tissues is located extracellularly.
Explore the source record for details and available documents.
Clomiphene citrate was administered as a 50 mg oral daily dose to 44 normogonadotrophic (serum FSH 2-10 mIU/ml) subfertile men for 3 months. The treatment resulted in significant increases in FSH and LH concentrations, whereas prolactin remained unchanged. Serum testosterone and oestradiol both increased highly significantly. The increased testosterone levels suggest that the elevated LH levels had not led to "down regulation" of Leydig cell LH/hCG receptors, neither had the greatly increased estradiol led to depletion of these receptors. This is suggested to be a result of the blocking of testicular oestradiol receptors by the estrogen antagonist, clomiphene. Sperm count increased highly unchanged. The spermatic fluid concentrations of zinc and magnesium ions were also increased, whereas fructose remained unchanged. The katalytic activity of acid phosphatase in spermatic fluid increased highly significantly, whereas the concentration of the main prostate-specific acid phosphatase, as measured by a specific radioimmunological method, remained unchanged. Therefore, the increased Zn and Mg ion concentrations may be responsible for activation of acid phosphatase (s) in semen, or the treatment led to increased secretion of other prostatic acid phosphatase(s) than the main enzyme. However, it is clear that the secretion of the main prostatic acid phosphatase into semen is under different control than that of Zn++ and Mg++.
The effect of antioestrogen treatment on the human testicular response to hCG was investigated in 17 adult men to further clarify the role of endogenous oestradiol in the regulation of testicular steroidogenesis. Clomiphene citrate was administered in 2 different modes. Group 1 (n = 8) was treated for 6 days (100 mg of the antioestrogen once a day) and a single dose of hCG (5000 IU im) was given at the beginning of the experiment. In group 2 (n = 9), the treatment was started 7 days prior to the hCG injection and was continued for additional 6 days. In both groups peripheral blood samples were collected up to 6 days after hCG, and the sera were analysed for FSH, prolactin and 8 steroids. In group 1, the steroidogenic response was identical to that found previously in untreated men. In group 2, the 7-day treatment with clomiphene citrate led to elevated serum concentrations of LH, FSH, pregnenolone, 17-hydroxyprogesterone, dehydroepiandrosterone, androstenedione, testosterone, 5 alpha-dihydrotestosterone and oestradiol. When compared with these elevated values, the response of serum 17-hydroxyprogesterone, dehydroepiandrosterone, androstenedione and testosterone to hCG were diminished. The ratios of the steroid concentrations support previous reports that hCG-induced inhibition of 17-hydroxylase, 17--20 desmolase and 3 beta-hydroxysteroid dehydrogenase-delta 4-5 isomerase is decreased during antioestrogen administration. This further substantiates the idea of a central role for endogenous testicular oestradiol in the mediation of steroidogenic lesions following acute large doses of hCG.
The postnatal pituitary-gonadal function of fullterm and premature boys and girls (mean gestational age, 40 and 32 weeks, respectively) was studied by measurements of serum FSH, LH, PRL, and testosterone (T) between 0-25 weeks of postnatal age. During the first 10 postnatal weeks, serum FSH in premature girls reached 10-20 times higher levels than in fullterm girls (mean at 1-5 weeks, 63 and 3.9 mIU/ml, respectively; P < 1.001). During the same time, serum LH levels were 3-4 times higher in premature (12-17 mIU/ml) than in fullterm girls (3.8-4.7 mIU/ml; P < 0.01). In contrast, no difference in serum gonadotropin levels were observed between premature and fullterm boys. Serum T in premature boys (mean, 2.95 ng/ml) reached a significantly higher level (P < 0.01) than in fullterm boys (1.45 ng/ml) from 11-15 weeks of age. The results emphasize the importance of the last weeks of gestation for the functional maturation of the fetal hypothalamic-pituitary-gonadal axis. Interruption of this maturational process by premature birth results in enhanced pituitary gonadotropin production in girls and increased testicular T production in boys.
Explore the source record for details and available documents.
Clinical and experimental studies have indicated that a nonsteroidal antiestrogen, clomiphene citrate, might prevent the stimulatory action of estrogens on the human endometrium. To investigate the mechanisms of this effect, the treatment of 19 postmenopausal patients with conjugated estrogens for 6 months was supplemented cyclically for 10 days with clomiphene citrate after every 7 weeks. Ten patients ingested clomiphene citrate alone, whereas 9 patients continued estrogen treatment during clomiphene supplementation. Estrogen and progestin receptors were measured from the cytosol of the endometrium after the first estrogen period and after the first and third clomiphene treatment. The estrogen receptor concentration was significantly lower after both clomiphene supplementation periods than after the initial estrogen administration. The progestin receptor concentration was significantly lower only after the first clomiphene citrate period. The effect of clomiphene citrate was independent of the initial histological appearance of the endometrium and led to atrophy of the endometrium in most of the patients. Because the effect of clomiphene citrate was independent of simultaneous estrogen administration, it acted as a pure antiestrogen in this treatment modality. The relative decreases in estrogen and progestin receptor concentrations on the present treatment regimen were different from those previously found on progestin treatment and most likely occur via different mechanisms. It is not known whether these two treatment types will have additive effects.
Explore the source record for details and available documents.
Prostate tissues removed from patients with benign prostatic hypertrophy were separated into epithelia and stromal components and 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 these two fractions were determined by radioimmunoassays after the purification of solvent steroid extracts by Lipidex-5000 column chromatography. On a 'per cell' basis (i.e. relative to DNA), testosterone was equally distributed between the two components, while the other androgens measured were more abundant in the stroma. The observation that 5 alpha-reduced androgens (especially 5 alpha-dihydrotestosterone) were more concentrated in the stroma, and that significant correlations between concentrations of metabolically related androgens were more common in the stroma than in the epithelium, indicate that the stroma is an important site of androgen metabolism in benign prostatic hypertrophic tissues. The present data also support the suggestion that 5 alpha-dihydrotestosterone produced in the prostatic stroma may be transferred to the epithelium by way of sex hormone binding globulin in the extracellular spaces of the prostate.
Cyproterone acetate (100 mg daily on the 5th-14th days of the normal cycle) together with ethinyl estradiol (0.05 mg daily on the 5th-25th days) was used for the treatment of hirsutism in 23 women for six months. This treatment caused a significant decrease in the severity of the hirsutism after only three months, the effect being maximal after six months. Sixty per cent of our patients reported being subjectively satisfied with the results. A relapse occurred, however, within three months of the end of the treatment in half the patients. The serum testosterone was significantly decreased after three months of treatment, but the changes in serum testosterone did not follow the changes in the clinical picture of hirsutism, suggesting that one facet in the favorable action of cyproterone acetate is an inhibition of the action of androgen on target cells. Various side effects, such as nausea, headache, loss of libido and depression, were reported very frequently, which undoubtedly limits the large scale use of this treatment, at least with the doses used in this study.
Explore the source record for details and available documents.
Explore the source record for details and available documents.