Biomedical subjects

R Balducci

Publications and source records attributed to R Balducci.

At least 37 records · Page 2Linked to original sources

PubMed1990

Bioactive and peripheral androgens in prepubertal simple hypertrichosis.

Prepubertal simple hypertrichosis is characterized by excessive growth of vellus hair in children without other signs of endocrinopathies. The aetiology is unknown and it is not clear if it is an abnormal entity or an extreme form of the normal range of hair growth. Sixteen girls (aged 7 +/- 1.9 years, mean +/- SD) with prepubertal simple hypertrichosis and, as controls, 12 normal age-matched girls were studied. All patients were in preadrenarchal age and in all patients an ACTH test was performed to exclude non-classical forms of congenital adrenal hyperplasia. Testosterone (T), androstenedione (A), dehydroepiandrosterone sulphate (DHA-S), dihydrotesterone (DHT), 3 alpha-androstanediol (3Ad) and its glucuronide (3AG), and sex hormone binding globulin (SHBG) were evaluated and free testosterone (FT) and T/SHBG ratio were calculated in all subjects. In all patients we found T, A and DHA-S plasma levels comparable to controls, excluding an increased glandular androgen secretion. No significant differences, compared to controls, were observed for SHBG, FT and T/SHBG ratio, suggesting a normal T bioavailability. DHT plasma levels were significantly increased with respect to controls (0.42 +/- 0.04 vs 0.11 +/- 0.03 nmol/l; P less than 0.002) whereas 3Ad and 3AG were comparable to controls. The very significant increase in DHT plasma levels, without a parallel increase in 3Ad and 3AG found in our cases with prepubertal simple hypertrichosis, is difficult to explain. The clinical and biochemical significance of the high DHT plasma values needs more investigation.

Androgens↗

PubMed1990

Ovarian 17-ketosteroid reductase deficiency as a possible cause of polycystic ovarian disease.

The deficiency of ovarian 17-ketosteroid reductase (17-KSR) was recently discovered to be a possible cause of polycystic ovarian disease (PCOD) in hirsute women. Forty three patients with PCOD (age range, 18-38 yr) were reevaluated to search for a hormonal pattern that might suggest an ovarian 17-KSR deficiency. Androstenedione, testosterone, FSH, LH, 17-hydroxyprogesterone, and dehydroepiandrosterone sulfate were evaluated basally on the day 17 of the menstrual cycle, when present, and after dynamic tests (ACTH stimulation, 1 mg im for 2 consecutive days; dexamethasone inhibition, 0.5 mg four times a day for 14 days; and cyproterone acetate treatment, 50 mg each day for 14 days) in three successive menstrual cycles or at 30-day intervals. All patients studied presented with hyperestronemia, abnormal gonadotropin pattern, and hyperandrogenism, but showed different responses of androstenedione and testosterone to dynamic tests. In two patients the hormonal pattern suggested an ovarian 17-KSR deficiency: in fact they showed plasma values of androstenedione (22 and 31.3 nmol/L, respectively) and estrone (628 and 849 pmol/L, respectively) that were greatly increased compared with other patients and with controls. Androstenedione did not increase after ACTH stimulation (21.5 and 32.1 nmol/L, respectively) and did not decrease after dexamethasone inhibition (21 and 29 nmol/L, respectively), but only decreased after cyproterone acetate treatment (8 and 10.8 nmol/L, respectively). An hCG test, performed during dexamethasone suppression, confirmed the diagnosis of ovarian 17-KSR defect in one of these two patients (patient 1). Two of three brothers of patient 1 (aged 25 and 34 yr) presented with persistent important pubertal gynecomastia; one brother also had severe oligospermia. These clinical findings and the high values of androstenedione/testosterone (0.85) and estrone/estradiol (4.1) ratios of baseline plasma levels compared with controls (0.18 and 2.1, respectively) suggested a partial testicular 17-KSR deficiency. Five other patients showed PCOD secondary to nonclassic 21-hydroxylase defect diagnosed on the basis of high 17-hydroxyprogesterone plasma values and highly responsive to ACTH. The remaining 36 patients showed increased values of androstenedione and testosterone after ACTH stimulation and a decrease of these two parameters after both dexamethasone inhibition and cyproterone acetate treatment. The discovery of the 17-KSR deficiency in men and women in the same family demonstrates genetic control of this enzyme similar in both sexes, confirming the hypothesis that this disorder is inherited as an autosomal recessive character. Finally, it is strongly supported that ovarian 17-KSR defect may cause a syndrome closely resembling PCOD.

17-Hydroxysteroid Dehydrogenases↗

PubMed1989

Changes in steroid pattern following acute and chronic adrenocorticotropin administration in premature adrenarche.

Biochemically adrenarche is characterized by increased production of 5-ene steroids, in particular Dehydroepiandrosterone (DHA) and its sulphate (DHA-S). It is still not clear if ACTH is responsible for this adrenal steroid production. The aim of the present study was to evaluate the effect of acute and chronic ACTH administration, without dexamethasone pretreatment, on hormonal patterns in 20 patients (5 males aged between 6 8/12 and 7 10/12 years and 15 females aged between 5 9/12 and 7 6/12 years) with idiopathic premature adrenarche. Pregnenolone (5P), DHA, DHA-S, 17-hydroxyprogesterone (17-OHP), androstenedione (A), 11-deoxycortisol (S) and cortisol (F) have been determined by Radioimmunoassay. The results of the hormonal evaluation (means +/- standard error) showed high plasma levels of DHA [329.2 +/- 41.7 ng/100 ml (dl)] and DHA-S (169.1 +/- 54 micrograms/dl) and slightly increased levels of 5P (74.4 +/- 7.1 ng/dl), of A (45.4 +/- 4.6 ng/dl) and 17-OHP (69.3 +/- 11.3 ng/dl) in comparison to those of controls, thus indicating a decrease in 3 beta-hydroxysteroid dehydrogenase activity and an increase in 17-20-lyase and 17-hydroxylase activities, characteristic for adrenarche. Acute and chronic ACTH stimulation did not amplify the characteristic basal hormonal pattern, but they induced a shift of adrenal steroid metabolism to 4-ene pathway, suggesting that the basal hormonal pattern in premature adrenarche may be independent or, at least, not exclusively dependent on ACTH control.

17-alpha-Hydroxyprogesterone↗

PubMed1989

Testicular responsiveness to a single hCG dose in patients with testicular feminization.

The suggestion that androgens may regulate testosterone (T) production in rat Leydig cells by a receptor-mediated feed-back mechanism, led us to investigate whether in vivo the absence of testicular androgen receptors, as it occurs in testicular feminization (TF), may modify the characteristic testicular response observed in men and prepubertal children after a single dose of hCG. Subjects consist of: 1) six normal men, 2) two adult patients with the complete form of androgen insensitivity syndrome (TF), 3) 12 normal prepubertal boys, 4) one prepubertal boy with the same form of TF. Each subject received i.m. a single dose of hCG 3500 IU/m2 b.s. and blood samples were collected basally and 2, 4, 24, 48, 72 and 96 hours after the hormonal stimulus. Serum levels of T, 17 alpha hydroxyprogesterone (17OHP) and 17 beta estradiol (E2) were measured at each collection time. In normal men a significant increase in T (M +/- SE) was observed at 4 h (758.6 +/- 135 ng/dl, P less than 0.05) and a more significant increase at 48 h (1082 +/- 60.3 ng/dl, P less than 0.001). E2 and 17OHP peaked significantly at 24 h (81.5 +/- 9.6 pg/ml and 460.7 +/- 90.9 ng/dl respectively). This response pattern is characteristic of the testicular desensitization which occurs in normal man after a single hCG dose. The same response pattern has been observed in the two TF adult patients suggesting that human testicular desensitization in vivo does not depend on androgen receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

17-alpha-Hydroxyprogesterone↗

PubMed1988

Bile acids with a cyclopropyl-containing side chain. 3. Separation, identification, and properties of all four stereoisomers of 3 alpha,7 beta-dihydroxy-22,23-methylene-5 beta-cholan-24-oic acid.

3 alpha,7 beta-Dihydroxy-22,23-methylene-5 beta-cholan-24-oic acid (CUDCA) (2a), a side-chain cyclopropylog of ursodeoxycholic acid (UDCA) was shown to be a mixture of four stereoisomers (CUDCA A-D). The 22S,23R, and 22R,23S diastereoisomers have been separated, their respective configurations assigned by 13C NMR spectroscopy, and original synthetic schemes for their preparation elaborated. Moreover, theoretical models of the structure of UDCA and CUDCA A-D were built by using molecular computer graphic techniques. It was shown that the four diastereoisomers greatly differ in hydrophilicity, in critical micellar concentration (CMC) in water, and exhibit a different interaction with intestinal bacterial enzymes. It was also shown that CUDCA A-C are not conjugated with glycine or taurine in the liver, while CUDCA D is secreted into bile predominantly as taurine and glycine conjugate.

Animals↗

PubMed1987

Lack of correlation between sex hormone binding globulin and free testosterone in some cases of "idiopathic" hirsutism.

Plasma 3 alpha-androstanediol levels are increased in a high percentage of hirsute women, including those with normal plasma levels of its precursors, repeatedly evaluated during the menstrual cycle. To better ascertain the origin of this form of hirsutism, so called "idiopathic", 17 hirsute women (aged 19.5 +/- 4.8 SD yr), with normal bw, showing an isolated increase in plasma 3 alpha-androstanediol (0.65 +/- 0.18 SD nmol/l) were studied in basal conditions (on day 6, 7, 17, 18 of the menstrual cycle). A hirsute female (aged 14 yr) with congenital adrenal hyperplasia due to 21-hydroxylase deficiency was also included in the protocol. Sex hormone binding globulin was evaluated using a saturation method (dihydrotestosterone- 3H 0.5-25 nM) with and without 200x cold dihydrotestosterone. Maximum number of binding sites and Ka were calculated in all cases with Scatchard analysis. Free testosterone was evaluated by the equilibrium dialysis technique. The results obtained showed a significant increase in Ka values in 10 out of the 17 cases; low plasma levels of sex hormone binding globulin in 13 cases and normal levels in 4 cases; high levels of free testosterone fraction in 5 cases and in the upper limits of the normal range or normal in the remaining 12. These findings demonstrate that some cases of "idiopathic" hirsutism may present an alteration in the binding affinity of the sex hormone binding globulin which may be genetically transmitted, being found to be increased in two sisters and in their brother.

Adolescent↗

PubMed1987

Testicular responsiveness following chronic administration of hCG (1500 IU every six days) in untreated hypogonadotropic hypogonadism.

The observation that the testosterone (T) response to a single intramuscular injection of hCG is prolonged suggests that currently used regimens (2-3 injections per week) to stimulate endogenous androgen secretion in hypogonadotropic hypogonadism (HH) patients have to be reassessed. Moreover, during the last few years, Leydig cell steroidogenic desensitization has been found after massive doses of hCG. The aim of the present investigation, carried out in 6 HH patients who showed no signs of puberty, was to study the effect of 1500 IU hCG administered every six days over a period of one year to induce the onset of pubertal development. To evaluate the kinetics of the response of T, 17 alpha-hydroxyprogesterone (17 alpha-OHP) and 17 beta-oestradiol (E2), blood samples were taken basally and 1, 2, 4 and 6 days after drug injection. This dynamic study was performed after the first injection and after the 4th and 12th month of treatment. During this one year time period, a progressive increase in testicular size was observed. Comparing plasma T levels (mean +/- SE) before the first injection (11.2 +/- 4.7 ng/dl) with the corresponding values at the 4th (38.7 +/- 10.5 ng/dl) and 12th months (99.5 +/- 19.9 ng/dl) of therapy, a progressive and significant increase was observed. T reached a maximum elevation 58 hours after hCG injection at the 4th month (198.3 +/- 42 ng/dl; P less than 0.01) and at the 12th month (415.6 +/- 62.6 ng/dl; P less than 0.05), whereas it remained unchanged following the first hCG injection.(ABSTRACT TRUNCATED AT 250 WORDS)

17-alpha-Hydroxyprogesterone↗

PubMed1987

Bile acids with a cyclopropyl-containing side chain. IV. Physicochemical and biological properties of the four diastereoisomers of 3 alpha,7 beta-dihydroxy-22,23-methylene-5 beta-cholan-24-oic acid.

To define the influence of the side chain modification on physicochemical and biological properties of bile acids, 3 alpha,7 beta-dihydroxy-22,23-methylene-5 beta-cholan-24-oic acid, a cyclopropyl analog of ursodeoxycholic acid (UDCA) was synthesized in both unconjugated and taurine-conjugated form. The presence of a cyclopropyl ring at C-22, C-23 position introduces chirality generating four diasteroisomers (A, B, C, and D) which greatly differ for the hydrophilicity and critical micellar concentration: A and B are more hydrophilic (K' = 0.21, 0.80 and CMC = 25,20 mM, respectively) than UDCA (K' = 0.95; CMC = 19 mM) while C and D are more hydrophobic and with lower CMC (K' = 1.30, 2.05; CMC = 14, 10 mM, respectively) than UDCA. Differences in these properties are related to the orientation of the C-25 carboxyl which in isomers A and B is oriented toward the back of the steroid body, reducing the continuity of the hydrophobic area. Using the isolated perfused rat liver we found that the isomers inhibited [3H]UDCA uptake differently. Isomer D (noncompetitive) was the most potent (51%) while isomer A (competitive) was the least potent (15%). When infused intravenously to rats, only D isomer and UDCA were quantitatively recovered in bile. They were secreted predominantly as taurine and glycine conjugates. Isomers A, B, C are not conjugated and only partially recovered in bile as unconjugates (less than 15% of the administered dose). The increase in bile flow per unit increase in bile acid secretion induced by isomers A, B, and C, was much greater than that induced by isomer D which is similar to that of UDCA (0.32 +/- 0.04 and 0.22 +/- 0.01, respectively) while it is reduced during infusion of the other isomers. When infused as taurine conjugates they behaved similarly to tauroursodeoxycholic acid. When incubated in anaerobic conditions with human stools only isomer D is partially 7-dehydroxylated (t/2 = 18 hr) even though slower than UDCA (t/2 = 5 hr). The substrate specificity of the taurine conjugated toward cholyglycine hydrolase is very poor, only isomers C and D are partially deconjugated with a kinetics much slower than that of UDCA (10 hr vs. 0.2 hr). By using molecular models it is possible to explain these differences due to the conformation of the side chain that, in the case of isomer D, is quite similar to UDCA. These data are useful to explain the metabolism of dihydroxy bile acids and to design new analogs with enhanced cholelitholytic activity.

Animals↗

PubMed1985

Familial male pseudohermaphroditism with gynaecomastia due to 17 beta-hydroxysteroid dehydrogenase deficiency. A report of 3 cases.

Three sisters with male pseudohermaphroditism due to 17 beta-hydroxysteroid dehydrogenase deficiency are described. On the basis of a 46 XY karyotype and female phenotype all subjects were thought to have the testicular feminization syndrome. At puberty the two older patients developed signs of virilization and gynaecomastia. In these patients the plasma androstenedione level was 4-5 times higher than normal, whilst the plasma testosterone level was low compared to the normal range and, under basal conditions, their plasma androstenedione to testosterone ratio was 20-25 times higher than normal. Interestingly, in the third, prepubertal case, the basal androstenedione to testosterone ratio was normal but became six times higher than normal after hCG stimulation. These data support the diagnosis of male pseudohermaphroditism due to 17 beta-hydroxysteroid dehydrogenase deficiency and underline the diagnostic value of the hCG stimulation test prepubertally.

17-Hydroxysteroid Dehydrogenases↗

PubMed1985

Spermatic and peripheral venous plasma concentrations of testosterone, 17-hydroxyprogesterone, androstenedione, dehydroepiandrosterone, delta 5-androstene-3 beta,17 beta-diol, dihydrotestosterone, 5 alpha-androstane-3 alpha,17 beta-diol, 5 alpha-androstane-3 beta,17 beta-diol, and estradiol in boys with idiopathic varicocele in different stages of puberty.

Serum testosterone (T), 17-hydroxyprogesterone (17P), androstenedione (delta 4-dione), dehydroepiandrosterone (DHA), delta 5-androstene-3 beta, 17 beta-diol (delta 5-diol), estradiol (E2), dihydrotestosterone (DHT),5 alpha-androstane-3 alpha,17 beta-diol (3 alpha diol), and 5 alpha-androstane-3 beta,17 beta-diol (3 beta diol) were measured in the peripheral and spermatic venous blood of 21 boys undergoing surgery for idiopathic left varicocele. The boys were divided into 3 groups according to their pubertal development: prepubertal (group 1 or P1; n = 8), pubertal stage 2 (group II or P2; n = 6), and pubertal stages 3-4 (group III or P3-4; n = 7). The testes of the prepubertal boys secreted T, 17P, DHA, delta 5-diol, DHT, and 3 alpha diol, but not delta 4-dione, E2, and 3 beta diol. In pubertal stage P2, the mean spermatic-peripheral secretory gradients of T, 17P, DHA, delta 5-diol, DHT, and 3 alpha diol were significantly higher than those in the prepubertal stage, and there was testicular secretion of delta 4-dione, E2, and 3 beta diol. In pubertal stage P3-4, the mean spermatic-peripheral secretory gradients of most of these steroids, even if increased, were not significantly different from those in stage P2 (with the exception of 17P, delta 5-diol, and DHA). We suggest that after the important modifications of testicular secretion occurring in pubertal stage P2, the testicular secretory pattern of the pubertal testis is similar to the pattern of the adult testis. We suggest also that these results, obtained in boys with idiopathic varicocele, can probably be extended to the secretory activity of the testes of normal pubertal boys.

17-alpha-Hydroxyprogesterone↗

PubMed1983

Response to a single dose of human chorionic gonadotropin in prepubertal boys.

In normal men a single dose of hCG induces an increase in plasma testosterone (T) and 17 alpha-hydroxyprogesterone (17 alpha-OHP) 2-4 h after the injection; after 24-36 h a maximum increase in plasma 17 beta-estradiol (E2) and 17 alpha-OHP occurs followed by a second surge in T after 48-96 h. The present investigation focuses on the effect of a single dose of hCG (3500 IU/m2 body surface) on testicular steroid production in 12 boys aged 13 months to 12 yr. Plasma hCG, 17 alpha-OHP, androstenedione (A), T, dihydrotestosterone, and E2 were measured basally and 2, 4, 24, 48, 72, and 96 h after hCG administration. Plasma hCG was measured using a double antibody RIA technique and steroids by RIA after celite chromatography. The results show that hCG peaked 2 h after administration of the hormone and high levels persisted for up until 72 h. Plasma T and dihydrotestosterone increased after 48 h and remained significantly high for another 48 h; 17 alpha-OHP, A, and E2 did not change. These findings show that hCG stimulation in prepubertal boys induces significant production of T without affecting the precursors or aromatization product, in contrast to observation in the adult man, where 17 alpha-OHP, A, and E2 increase significantly. A response comparable to that observed in children has been recorded in adult males with hypogonadotropic hypogonadism.

Aging↗

PubMed1982