Search PubMed⌕ Search

Biomedical subjects

R Vihko

Publications and source records attributed to R Vihko.

At least 109 records · Page 6Linked to original sources

Response of serum testosterone and its precursor steroids, SHBG and CBG to anabolic steroid and testosterone self-administration in man.

The influence of high doses of testosterone and anabolic steroids on testicular endocrine function and on circulating steroid binding proteins, sex hormone binding globulin (SHBG) and cortisol binding globulin (CBG), were investigated in power athletes for 26 weeks of steroid self-administration and for the following 16 weeks after drug withdrawal. Serum testosterone and androstenedione concentrations increased (P less than 0.05) but pregnenolone, 17-hydroxypregnenolone, dehydroepiandrosterone, 5-androstene-3 beta, 17 beta-diol, progesterone and 17-hydroxyprogesterone concentrations strongly decreased (P less than 0.001) during steroid administration. Serum pregnenolone, 17-hydroxypregnenolone and dehydroepiandrosterone sulphate concentrations followed the changes of the corresponding unconjugated steroids but 5-androstene-3 beta, 17 beta-diol and testosterone sulphate concentrations remained unchanged during the follow-up time. During drug administration SHBG concentrations decreased by about 80 to 90% and remained low even for the 16 weeks following steroid withdrawal. Steroid administration had no influence on serum CBG concentrations. In conclusion, self-administration of testosterone and anabolic steroids soon led to impairment of testicular endocrine function which was characterized by low concentrations of testosterone precursors, high ratios of testosterone to its precursor steroids and low SHBG concentrations. Decreased concentrations of SHBG and testicular steroids were still partly evident during the 16 weeks after drug withdrawal. The depressed circulating levels of dehydroepiandrosterone and its sulphate may indicate that the androgenic-anabolic steroids also suppress adrenal androgen production.

17-alpha-Hydroxypregnenolone↗

Short-term effects of testolactone on human testicular steroid production and on the response to human chorionic gonadotropin.

Testicular responsiveness to a single dose of human chorionic gonadotropin was studied in five normal men before and during short-term treatment with an aromatization inhibitor, testolactone (TL). TL alone resulted in significant increases in the serum concentrations of progesterone, 17-hydroxyprogesterone, 17-hydroxypregnenolone, dehydroepiandrosterone, androstenedione, and the sulfate conjugates of pregnenolone, 17-hydroxypregnenolone and testosterone (T). Concentrations of 5-androstene-3 beta, 17 beta-diol and T remained unchanged, and those of estradiol (E2) decreased. TL had no major influence on serum luteinizing hormone, follicle-stimulating hormone, prolactin, or sex-hormone-binding globulin concentrations. During TL administration, human chorionic gonadotropin stimulation led to a significantly decreased E2 response, but the T response was unchanged. Alleviation of an inhibitory influence of E2 on the steroidogenic enzymes, especially 17,20-desmolase, was probably the reason behind the increased synthesis of several T precursors. In addition, TL appeared to have an inhibitory influence on the 17 beta-reduction of T precursors. TL resulted in increased serum concentrations of some steroid sulfates, but the mechanism of this effect remains unclear.

Adult↗

Effect of gestrinone in endometriosis tissue and endometrium.

The effects of gestrinone (R 2323) on endometrial and endometriosis tissue concentrations of cytosol estrogen and progestin receptors and the activity of 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) were investigated in 11 patients operated on because of suspected external endometriosis. Serum concentrations of luteinizing hormone, follicle-stimulating hormone, estradiol (E2), progesterone, testosterone (T), and sex-hormone-binding globulin (SHBG) were also investigated. After one control cycle, the patients received 2.5 mg of oral gestrinone twice weekly from the fifth day of the first treatment cycle until the eighth day of the second treatment cycle, the day of operation being day 10. Treatment with gestrinone decreased serum concentrations of T during the second treatment cycle and effected a major decrease in SHBG during both treatment cycles, resulting in highly increased free T and free E2 indices. The effects of gestrinone on the endometrium, a decrease in estrogen and progestin receptors, and induction of 17 beta-HSD are characteristic progestin actions. These parameters remained unchanged in endometriosis tissue. Our data indicate that gestrinone has effects that are typical of androgens and progestins in patients with endometriosis.

17-Hydroxysteroid Dehydrogenases↗

Immunoreactive prostatic acid phosphatase in prostatic cancer: diagnosis and followup of patients.

We compared the measurements of serum acid phosphatase activity to those obtained by radioimmunoassay of prostatic acid phosphatase in the sera of 126 untreated prostatic cancer patients. The catalytic activity of prostatic acid phosphatase was elevated in 32 per cent of the patients and the serum concentration of prostatic acid phosphatase was elevated in 66 per cent. Of these 126 patients 16 had stage T0-2M0N0-x disease, and enzyme activity and prostatic acid phosphatase concentration were increased in 0 and 38 per cent, respectively, in this group. Of the 110 patients with proved extracapsular cancer the corresponding figures were 36 and 70 per cent, respectively. We followed 109 of these 126 patients for 1 or more years after orchiectomy. A salient finding was that return of elevated serum prostatic acid phosphatase concentration to the health-associated reference interval within 7 days following castration indicated no progression of the disease at 1 year irrespective of the initial staging. The same was not detected by the measurement of catalytic activity of serum acid phosphatase. Our findings substantiate data showing that the measurement of circulating prostatic acid phosphatase is achieved better by immunological techniques than by measurements of catalytic activity of the enzyme. A novel aspect is the usefulness of immunological prostatic acid phosphatase measurements in evaluation of the prognosis of patients with metastatic prostatic carcinoma following ablative endocrine treatment.

Acid Phosphatase↗

Premenarcheal endocrine changes in relation to age at menarche.

Pubertal development preceding menarche in normal girls having menarche at a relatively early age (11.3-12.9 years) was compared with the development of girls having menarche later (13.0-14.9 years of age). Eighty-four premenarcheal girls, 7.3-14.3 years old, were examined and their age at menarche was recorded during this longitudinal study. Girls with early menarche had a larger increase in serum oestradiol at about 10 years of chronological age, and after that age the concentrations remained higher than in girls having later menarche. Serum FSH concentrations tended to be slightly higher at the onset of puberty in the former group, even before differences in serum oestradiol concentrations were observed. Pubertal development was faster in girls having early menarche, as indicated by the significantly shorter time from both breast and public hair stage 2 to menarche. This rapid sequence can be related to the higher oestradiol levels. A dissociation between gonadarche and adrenarche was evident. The oestradiol/dehydroepiandrosterone (DHEA) ratio was higher in girls developing early menarche. Around the onset of puberty (9.0-11.5 years of age) there was a complete lack of correlation between serum DHEA concentrations and age at menarche, whereas serum FSH and oestradiol concentrations displayed strong correlations with age at menarche. The present data support the view that girls with early menarche have a more profound decrease in the sensitivity of the hypothalamic-pituitary unit to the negative feed-back of circulating steroids.

Adolescent↗

Steroidal regulation of endometriosis tissue: lack of induction of 17 beta-hydroxysteroid dehydrogenase activity by progesterone, medroxyprogesterone acetate, or danazol.

Cytosol and nuclear estrogen receptors were detected in 73% and 89% of untreated endometriosis specimens, respectively. The corresponding figures for cytosol and nuclear progestin receptors were 94% and 100%, respectively. Compared with the endometrium, the concentrations in endometriosis tissue were low. The anatomic site, the severity of the disease, and the phase of the menstrual cycle had no significant influence on receptor concentrations in endometriosis tissue. The activities of 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) did not increase during the luteal phase. Danazol for 1, 3, 7 to 11, and 18 to 30 days, or medroxyprogesterone acetate for 5 days, had no effect on receptor concentrations or 17 beta-HSD activity in endometriosis tissue. The frequent presence of the receptors suggests that endometriosis lesions are under the control of steroid hormones. The lack of effect by progesterone and progestins on 17 beta-HSD shows that this regulation is different in endometriosis tissue and in the endometrium.

17-Hydroxysteroid Dehydrogenases↗

Response of serum hormones to androgen administration in power athletes.

Endocrine effects of self-administration of high doses of anabolic steroids and testosterone were investigated in five power athletes during 26 wk of training, and for the following 12-16 wk after drug withdrawal. After 26 wk of anabolic steroid and testosterone administration, serum testosterone concentrations had increased 2.3-fold. This was associated with increased concentrations of serum estradiol, which rose 7-fold to values (0.48 nmol X 1(-1) typical for females. There was a major decrease in serum FSH and LH concentrations, but they returned to control levels following drug withdrawal. However, serum testosterone concentrations stayed at low levels (9 nmol X 1(-1) ) during this follow-up period, indicating long-lasting impairment of testicular endocrine function. Serum ACTH concentrations were also decreased during steroid administration, possibly due to a corticoid-like effect of some of the anabolic steroids taken in high doses. However, no changes were seen in serum cortisol. The only consistent change in the control group was an increase in serum LH concentrations during the most intensive training, suggesting that a decreasing tendency of serum testosterone was compensated for by augmented LH secretion.

Adrenocorticotropic Hormone↗

Short-term effects of tamoxifen, medroxyprogesterone acetate, and their combination on receptor kinetics and 17 beta-hydroxysteroid dehydrogenase in human endometrium.

The interactions of an antiestrogen (tamoxifen) and a progestin (medroxyprogesterone acetate) on endometrial 17 beta-hydroxysteroid dehydrogenase activities were studied in short-term experiments (four to 96 hours) in normally menstruating women at the follicular phase and were related to simultaneously measured concentrations of cytosol and nuclear estrogen and progestin receptors. Tamoxifen effected a decrease in the activity of 17 beta-hydroxysteroid dehydrogenase. This was associated with an apparent translocation to and retention of estrogen receptor in the nucleus without any significant changes in cellular progestin receptor. Medroxyprogesterone acetate administration led to a rapid increase in endometrial 17 beta-hydroxysteroid dehydrogenase activity, and depletion of cytosol and total cellular progestin receptor. Combination of the drugs led to effects that could be addressed to the individual drugs separately, and under the experimental conditions the effects of medroxyprogesterone acetate were uninfluenced by simultaneous tamoxifen administration. Put together with the authors' previous findings on the same parameters during long-term (three-week) medroxyprogesterone acetate administration, it seems possible that potentiation of progestin effects on endometrial carcinoma is not to be expected during long-term simultaneous antiestrogen-progestin treatment. It is therefore likely that the favorable effects of combining these two drugs in long-term treatment are due to their different endocrine action mechanisms.

17-Hydroxysteroid Dehydrogenases↗

Endocrine characteristics of adolescent menstrual cycles: impact of early menarche.

An initial group of 200 girls, 7-17 years old, was investigated longitudinally 4 times at 1.5-, 1.5- and 5-year intervals. The present study gives information of the impact of early menarche, a risk factor for breast cancer, on some physical and endocrine characteristics in these subjects. The frequency of ovulation depended significantly on both the time since menarche and the age at menarche. Early menarche was associated with early onset of ovulatory cycles. Even in early puberty, before menarche, the subjects who displayed early menarche during follow-up had higher serum FSH and estradiol concentrations than the girls whose menarche took place after the age of 13.0 years. Adrenal androgen secretion (dehydroepiandrosterone) was not influenced by age at menarche but it increased, as expected, on the basis of chronological age. The group with early menarche was characterized by high circulating estradiol concentrations also after menarche, even in the oldest subjects so far studied, 17-25 years of chronological age. At these ages, the differences in the frequencies of ovulatory cycles were disappearing between the groups formed on the basis of age at menarche. The present findings in pre- and postmenarcheal subjects suggest that the increased risk of breast cancer associated with early menarche is created over several years of exposure to high-level estrogen stimulus.

Adolescent↗

Hormonal changes during the perinatal period: FSH, prolactin and some steroid hormones in the cord blood and peripheral serum of preterm and fullterm female infants.

Fetoplacental endocrine function during the last third of gestation, and first 5 days post partum, was studied by hormone measurements of umbilical cord arterial and venous serum in preterm (31-37 weeks gestation) and fullterm (39-42 weeks gestation) female newborn. Furthermore, hormones were measured in peripheral serum of fullterm female infants of 1, 3 and 5 days of age. The data were compared with those obtained previously in corresponding age groups of males. FSH was significantly (P less than 0.05) higher in the cord serum of preterm females (5.4 +/- 1.8 IU/I, SE, n = 30) than in males (1.5 +/- 0.08 IU/l, n = 27), and decreased significantly (P less than 0.05) in preterm females towards fullterm. PRL levels increased in both sexes towards the end of gestation (P less than 0.01), and decreased post partum, but no sex differences could be detected. Testosterone was significantly higher in the male serum samples (P less than 0.01-0.05), but only minor sex differences were seen in cord serum, or post partum, concentrations of the other steroids measured, pregnenolone, progesterone, 17-hydroxyprogesterone and androstenedione. Significant arterio-venous difference (higher in the vein) were seen at term in progesterone and 17-hydroxyprogesterone. The levels of these two steroids also decreased most clearly after birth. Female serum testosterone peaked at d 1 post partum (0.084 +/- 0.014 microgram/l, SE, n = 11), decreased thereafter, but remained at the intrauterine level, suggesting that the low female levels of this steroid are of fetal, rather than placental/maternal origin. The same seems to be true for androstenedione. Our data suggest that the fetal ovary is quiescent during the last weeks of gestation.

Androstenedione↗

Oestrogen and progesterone receptors and disease-free interval in primary breast cancer.

Oestrogen and progesterone receptor assays were performed in 286 women with primary breast cancer, and the patient group was followed up for a minimum of 24 months. Of the 263 patients belonging to clinical stages I-III and serving as the population used for calculation of disease-free interval only 1.9% received postoperative endocrine treatment and 6.5% chemotherapy. No significant relationship between the presence or concentrations of oestrogen or progesterone receptor and the disease-free interval was observed. It is therefore possible that the positive relationship between these variables reported in some investigations reflects an influence by adjuvant endocrine measures.

Breast Neoplasms↗

Hypergonadotropic hypogonadism in newborn males with primary testicular failure.

Four infants with genital ambiguity but with apparent testes were given a gonadotropin-releasing hormone (GnRH) test and a human chorionic gonadotropin (hCG) test at age 3-12 days. The results were compared with those from 16 newborn males (aged 2 to 6 days) with minor genital anomalies; 9 with unilateral and 3 with bilateral incomplete testicular descent, 2 with surgically insignificant glandular hypospadias and 2 with penis length less than (means-2 SD) for gestational age. Treatment with testosterone resulted in clear phallus growth in all four patients. All four patients had elevated basal luteinizing hormone (LH) concentrations as well as an exaggerated LH response to GnRH; three of them also had an exaggerated follicle stimulating hormone (FSH) response. Thus in all patients the etiology of genital ambiguity was considered to be testicular. The testosterone response to hCG was normal in two of the patients but impaired in the other two. The steroidogenic response did not show any specific enzyme defect. We conclude that newborn boys with Leydig cell failure are clearly hypergonadotropic, the GnRH test is a more sensitive indicator of Leydig cell failure neonatally than the hCG test and normal testes greatly inhibit the secretion of both LH and FSH during the first week of life.

Chorionic Gonadotropin↗

Correlation of estrogen and progesterone receptors and histological grade in human primary breast cancer.

The relationships between the presence of female sex steroid receptors and their concentrations, and the histological grade were investigated in primary breast carcinoma specimens from 151 patients. The concentrations of estrogen receptor were significantly lower in grade III tumours than in the more differentiated ones from pre- and post-menopausal patients, whereas the same was observed for progesterone receptor concentrations only between grades III and I in post-menopausal patients. Generally estrogen and progesterone receptor-positive, estrogen receptor rich tumours frequently belonged to well-differentiated tumour categories. Whereas most of the tumours belonging to grade III group were receptor-negative, approximately three fourths of receptor-negative tumours belonged to grade I and II categories. It is therefore suggested that estrogen receptor-negativity or low receptor concentrations and grade III histological appearance of breast carcinoma are independent risk indicators, and their concomitant use is recommended in designing treatment strategies for individual patients.

Breast Neoplasms↗

Responsiveness of the pituitary-testicular axis to gonadotropin-releasing hormone and chorionic gonadotropin during the first week of life.

Qualitative changes are known to occur in testicular steroidogenesis at birth as the testosterone peak is reached without significant elevation of basal luteinizing hormone in the 2nd wk of life. This study was designed to evaluate testicular activity prior to these changes. Pituitary-testicular function was studied by measuring serum gonadotropins and steroids after stimulation by gonadotropin-releasing hormone (GnRH) (one intravenous injection) and human chorionic gonadotropin (hCG) (three intramuscular injections). The subjects had minor genital anomalies; their ages ranged from 2 to 6 days. All had a strong luteinizing hormone response and a weaker follicle-stimulating hormone response to GnRH stimulation. hCG induced significant increases in serum pregnenolone, 17-hydroxyprogesterone, androstenedione, testosterone, and dihydrotestosterone. Serum estradiol and estrone did not change, and progesterone decreased. The results clearly show that the pituitary-testicular axis is functional neonatally. The responsiveness of the testis to hCG supports the assumption that the postnatal decrease of testicular steroids is due to the simultaneous disappearance of hCG from the circulation. The neonatal testis does not show any estradiol response to hCG, which is a feature typical of prepuberty.

Chorionic Gonadotropin↗