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Biomedical subjects

V Toscano

Publications and source records attributed to V Toscano.

At least 37 records · Page 2Linked to original sources
PubMed1995

Bone turnover and bone mineral density in young adult patients with panhypopituitarism before and after long-term growth hormone therapy.

We examined the effects of biosynthetic growth hormone (GH) on biochemical indices of bone turnover and on bone mineral density in a group of GH-deficient adults. Thirteen patients (eight males and five females) aged 24 +/- 5 years (range 16-35) were studied before and 12 and 24 months after GH treatment (0.1 IU.kg-1 day-1, 6 days a week). Serum levels of insulin-like growth factor I (IGF-I), calcitonin, parathyroid hormone, alkaline phosphatase, intact osteocalcin, fasting urinary hydroxyproline/creatinine ratio and bone mineral density (BMD), measured at the lumbar spine by dual-photon absorptiometry, were evaluated. After 12 months of treatment, IGF-I, alkaline phosphatase, osteocalcin and the fasting urinary hydroxyproline/creatinine ratio increased significantly. However, after 24 months of therapy, serum levels of osteocalcin decreased to pretreatment values while IGF-I, fasting urinary hydroxyproline/creatinine ratio and alkaline phosphatase remained elevated significantly. No changes were found in parathyroid hormone and calcitonin plasma levels or in BMD either after 12 or 24 months of treatment. These data demonstrate that GH, at the dosage that we used, activates bone turnover during 24 months of therapy in adults with panhypopituitarism, even if a downward trend for osteocalcin became apparent at 24 months. However, this activation in bone turnover was not accompanied by an increase in BMD. We can hypothesize that GH, at the relatively high dosage used, may stimulate osteoclastic activity to a greater extent than osteoblastic activity. It is probable that the dose of GH replacement therapy in adults plays a key role.

Adolescent↗
PubMed1995

Androgen-secreting adrenal tumors.

Virilizing adrenal tumours, adenomas and adenocarcinomas are rare and their clinical manifestations vary depending on age at onset. The paper reports the results obtained in 4 patients with adenoma and 3 with adenocarcinoma, as well as 11 cases of classic congenital adrenogenital syndrome by way of comparison. The hormonal status of adenomas is usually characterised by a predominant increase in plasma androstenedione (> 600, ng/dl) and testosterone (> 200 ng/dl), whereas carcinomas present a predominant hypersecretion of dehydroepiandrosterone (> 1200 ng/dl) and its sulphate (> 700 micrograms/dl). Plasma estrogen levels may also be enhanced due to active peripheral androgen conversion or direct secretion. 17alpha-hydroxyprogesterone, which is high in congenital adrenal hyperplasia, is normal or slightly enhanced, as is cortisol. Differential diagnosis must be made with androgen secreting tumours of the ovaries and, in males, with the various forms of precocious puberty, including endocrine tumours of the testicle, as well as congenital adrenogenital syndrome. A tumour with a diameter > 7 cm when examined using CT or NMR may be suspected as carcinoma, but malignancy cannot be excluded even in smaller tumours. Virilizing adrenal tumours do not usually respond to dexamethasone suppression test or ACTH stimulus since they do not express ACTH receptors or present post receptor anomalies. Steroidogenesis may be cAMP/protein-kinase independent and can be activated through alternative pathways. The presence of a stimulating G-protein has been detected in carcinomas which serves to activate adenylate cyclase on a permanent basis. b6 cytochrome is super-expressed and may be responsible for androgen over-secretion by activating 17,20-desmolase.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1994

Isolated precocious pubarche: an approach.

Precocious pubarche (PP) is most often a benign condition secondary to the early appearance of adrenarche. However, PP may be a manifestation of nonclassical adrenal hyperplasia. The incidence of nonclassical adrenal hyperplasia in patients with PP ranges from about 0-40% of cases. Controversy exists as to whether all children with PP should undergo an ACTH stimulation test. The aim of this study was 1) to determine the frequency of mild adrenal enzyme defects in a very large and ethnically homogeneous group of children with isolated PP (typical pubarche); 2) to determine whether clinical data, in particular bone age, and basal hormonal values can help to distinguish patients who are at risk for having adrenal enzymatic defects and thus should have an ACTH test; and 3) to determine which patients diagnosed as having a mild adrenal enzyme defect might require treatment. We studied 171 subjects (135 girls and 36 boys), aged 7 +/- 1.2 (SD) yr, with isolated PP. Thirty-eight normal subjects (18 age-matched and 20 pubertal) were studied as controls. An ACTH stimulation test (Synacthen, 0.25-mg iv bolus) was performed. Blood samples were drawn at baseline and 1 h postinjection. 17 alpha-Hydroxyprogesterone (17OHP), 17 alpha-hydroxypregnenolone (17PGN), dehydroepiandrosterone, androstenedione, testosterone, 11-deoxycortisol, and cortisol were evaluated. Haplotype (HLA) typing was performed in the patients who were diagnosed with nonclassical 21-hydroxylase deficiency (NC21OHD). Using published nomogram standards for the serum 17OHP response to ACTH, 10 patients (5.8%) were diagnosed as having NC21OHD. Seven of 112 patients (6.2%) were diagnosed as having nonclassical 3 beta-hydroxysteroid dehydrogenase deficiency (NC3HSD) on the basis of the following three criteria: stimulated 17PGN levels and stimulated 17PGN/17OHP and 17PGN/cortisol ratios higher than 2 SD above the mean for pubertal controls. None of the patients had stimulated 11-deoxycortisol values greater than 2 SD above the mean of pubertal controls. Nineteen patients (11%) had a stimulated 17OHP response characteristic of the heterozygotes for 21-hydroxylase deficiency. One hundred and thirty-five of 171 patients with no biochemical evidence of an adrenal biosynthetic defect were diagnosed as having precocious adrenarche. Bone age was advanced (> 2 SD for chronological age) in 80% of the patients with NC21OHD, in 71.4% of the patients with NC3HSD, in 58% of the patients classified as heterozygotes, and in 32.6% of the patients with precocious adrenarche. Basal hormone levels were helpful in detecting NC21OHD, but not NC3HSD. All patients with NC21OHD and only 1 with NC3HSD underwent glucocorticoid suppression treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

17-alpha-Hydroxypregnenolone↗
PubMed1993

Plasma 3 alpha-androstanediol glucuronide in precocious adrenarche.

The aim was to study 3 alpha-androstanediol glucuronide (3AG) plasma levels and its relationship with 5-ene and 4-ene steroids in children with the benign form of precocious pubarche (precocious adrenarche). Sixty-five children with precocious adrenarche (PA), aged 3.6-8.2 yr (55 girls and 10 males) and 15 normal age-matched children were studied. We evaluated plasma androstenedione (A), dehydroepiandrosterone (DHA), its sulfate (DHA-S), testosterone (T), dihydrotestosterone (DHT), its glucuronide (DHTG), 3 alpha-androstanediol (3Ad) and its glucuronide (3AG) in all subjects. All androgens are expressed as mean +/- SD. We found significantly higher plasma levels not only in glandular androgens but also in peripheral androgens (A, 2.4 +/- 1.5 nM vs 0.79 +/- 0.46 nM, p < 0.001; DHA, 9.8 +/- 4.9 vs 2.7 +/- 0.76 ng/dl, p < 0.001; DHA-S, 3.4 +/- 2 microM vs 2.4 +/- 0.65 microM, p < 0.05; T, 0.74 +/- 0.5 nM vs 0.4 +/- 0.1 nM, p < 0.001; DHT, 0.36 +/- 0.13 nM vs 0.12 +/- 0.05 nM, p < 0.001; 3Ad, 0.13 +/- 0.1 nM vs 0.054 +/- 0.03 nM, p < 0.001; DHTG, 0.5 +/- 0.3 nM vs 0.26 +/- 0.09 nM p < 0.01). As far as the plasma 3AG levels are concerned we found significantly higher values in PA with respect to controls (1.17 +/- 0.7 nM vs 0.61 +/- 0.04 nM, p < 0.01), suggesting that 3AG may be considered a marker of skin androgen utilization.(ABSTRACT TRUNCATED AT 250 WORDS)

Androstane-3,17-diol↗
PubMed1993

Relationship between epidermal growth factor and its receptor in human benign prostatic hyperplasia.

Human benign prostatic hyperplasia (BPH) samples were analyzed to evaluate the presence of immunoreactive epidermal growth factor (irEGF) and EGF receptor (EGFR). In all BPH samples examined both peptide and its receptor were present. Scatchard analysis of binding data of [125I]EGF showed two classes of binding sites with high and low affinity. Intratissular irEGF concentrations showed a significant inverse linear correlation with EGFR levels. Two groups of samples can be identified: the first showing high irEGF concentrations and low levels of EGF binding sites; the second low irEGF and high concentrations of EGFR. The simultaneous presence of EGF and its receptor in BPH samples indicates that this growth factor may act in an autocrine/paracrine manner in human prostatic tissue. The inverse relationship between EGF and the two sites of EGFR lead one to hypothesize that EGF itself could play a central role in determining receptor cell surface availability.

Aged↗
PubMed1993

Two different pathogenetic mechanisms may play a role in acne and in hirsutism.

OBJECTIVE: Acne is one of the most common skin disorders. Androgens are known to play an important and possibly central role. Androgens secreted from ovaries and adrenal glands (androstenedione, dehydroepiandrosterone and its sulphate, testosterone) and target tissue-produced androgens (testosterone and its 5 alpha-reduced metabolite, dihydrotestosterone) have been implicated. Although the sebaceous gland and the hair follicle form a single morphological entity, the pilosebaceous unit, acne and hirsutism do not always appear concomitantly, thus leading to the supposition that these two structures may have different degrees of sensitivity to similar androgenic stimulation. DESIGN AND PATIENTS: To determine whether acne and hirsutism are the clinical expression of a different androgen metabolism at target tissue levels we studied 90 randomly selected patients who came to our Out-patient Department for diagnosis and treatment during the last 2 years with isolated acne of mild to severe degree and 52 patients with idiopathic hirsutism without acne or history of acne. Twenty-four women without acne or hirsutism and without a history of endocrine disease were studied as controls. MEASUREMENTS: In both groups of patients, plasma levels of sex hormone binding globulin, of dihydrotestosterone, and of 3 alpha-androstanediol and of its glucuronide were evaluated. In all patients the percentage of free testosterone and the testosterone/sex hormone binding globulin ratio were also calculated. RESULTS: Patients with acne and those with isolated hirsutism showed significantly decreased sex hormone binding globulin plasma levels. The values of the percentage free testosterone and those of the testosterone/sex hormone binding globulin ratio were, on the contrary, higher with respect to the controls, although there were no statistically significant differences between the two groups. Significantly increased plasma levels of dihydrotestosterone with respect to the controls were observed in patients with acne or in those with hirsutism. However, while all patients with hirsutism showed increased plasma values of 3 alpha-androstanediol and its glucuronide, all patients with acne showed plasma levels within the normal range, independently of the precursor plasma levels. CONCLUSIONS: Our results demonstrate that dihydrotestosterone is further reduced to 3 alpha-androstanediol and its glucuronide only in hirsute patients but not in acne patients. These results suggest that dihydrotestosterone may undergo different metabolic pathways at skin levels and support the hypothesis that the two clinical manifestations may be the expression of the different metabolic fate of dihydrotestosterone itself. Moreover, our results demonstrate that 3 alpha-androstanediol and its glucuronide cannot be used as plasma markers of target-tissue produced androgens in all hyperandrogenic conditions.

Acne Vulgaris↗
PubMed1993

The effect of growth hormone administration on testicular response during gonadotropin therapy in subjects with combined gonadotropin and growth hormone deficiencies.

To evaluate the effect of growth hormone on testicular response to human chorionic gonadotropins (hCG) in vivo in humans, we selected patients with combined deficits of GH and gonadotropins who were in substitution treatment with both GH (from the time of diagnosis) and gonadotropins (from the time of induction of puberty). Testicular response to gonadotropin therapy was then evaluated during and six months after the cessation of GH treatment. Blood samples were collected before and 2, 4 and 6 days after hCG administration. hCG responses were calculated and expressed as the areas under the response curve. We studied four hypogonadotropic patients (aged 18-19 years) with associated GH deficiency. Their gonadotropin treatment consisted of hCG 1,500 IU every six days, and FSH 75 IU every three days. The GH therapy replacement consisted of 4 IU thrice weekly. Testosterone, androstenedione, 17 alpha-hydroxyprogesterone and estradiol were measured. In all subjects the testosterone area during GH treatment was significantly higher compared to the testosterone area obtained without GH administration (2993 +/- 1091 vs 2310 +/- 751; M +/- SD; p < 0.04). The androstenedione area followed a similar pattern (708 +/- 377 vs 402 +/- 248; M +/- SD; p < 0.05). The 17 alpha-hydroxyprogesterone area, on the contrary, was significantly higher during GH withdrawal (542 +/- 307 vs 235 +/- 190; M +/- SD; p < 0.05). As far as the estradiol area is concerned, no significant differences were found (22,860 +/- 10,082 vs 25,697 +/- 13,640; M +/- SD). In conclusion, GH administration seems to improve testosterone production induced by human chorionic gonadotropins.(ABSTRACT TRUNCATED AT 250 WORDS)

17-alpha-Hydroxyprogesterone↗
PubMed1992

Steroidal and non-steroidal factors in plasma sex hormone binding globulin regulation.

Sex hormone binding globulin (SHBG) is a specific steroid-binding plasma glycoprotein regulated by several factors. Sex steroids are currently considered to be the main physiological regulators of this protein. SHBG levels, in fact, increase during estrogen treatment and decrease after androgen administration. It is well known, however, that in many physiological and pathological conditions SHBG concentrations cannot be explained only on the basis of steroidal control mechanisms. The regulation of SHBG levels is in fact more complex and other factors can also affect its plasma values. Between the steroidal factors our attention was focused on the role of androgens, of glandular and peripheral origin, in their capacity to lower SHBG plasma levels. We studied hyperandrogenic conditions in prepubertal (65 subjects with precocious adrenarche and 16 girls with prepubertal hypertrichosis, aged between 4 and 8 years) and in adult age (51 hirsute patients aged between 14-35 years and 51 acneic patients aged between 15-40 years). The effects of dexamethasone and ACTH administration on SHBG plasma levels were also evaluated. The results obtained showed that in adult hyperandrogenic patients SHBG levels, significantly lower than in controls, were not always inversely correlated with androgen levels, which, on the contrary, were higher than in controls. In patients with precocious adrenarche we found an inverse correlation only between SHBG, which was significantly lower than normal, and body mass index or bone age but not with androgens, suggesting that in this condition other factors may be more relevant than steroids in SHBG regulation. Between the non-steroidal factors our attention focused on insulin. We studied 40 non-obese hyperandrogenic patients with or without ultrasonographic evidence of polycystic ovaries, aged 18-39 years, and 35 obese patients, aged 19-37 years, with or without hyperandrogenism or evidence of PCO. Low levels of SHBG were found not only in hyperandrogenic obese patients but also in obese patients with normal androgens. It is possible to conclude that (1) several factors (calorie intake, energy balance and growth factors), other than steroids, may be involved in the regulation of SHBG levels in plasma; and (2) each regulating factor may act to a different extent depending on the various periods of the life cycle.

Adolescent↗
PubMed1992

Immunoreactive EGF in human benign prostatic hyperplasia: relationships with androgen and estrogen receptors.

Benign prostatic hyperplasia (BPH) is a sex steroid dependent disease. Estrogens and androgens can modulate in different mammalian tissues epidermal growth factor (EGF) production and/or secretion. In order to clarify the relationships between estrogen and androgen receptor concentrations and those of immunoreactive EGF (irEGF), we have evaluated these parameters in 14 human BPH samples, by means of a dextran-coated charcoal method and radioimmunoassay, respectively. Cytosolic steroid receptors did not seem to correlate with irEGF. A linear significative relationship was evident between nuclear androgen receptor (ARn) levels and endogenous irEGF but not between nuclear estrogen receptors and irEGF: in ARn negative BPH samples, irEGF levels were lower than in ARn positive ones. Therefore, it is possible that androgens act at prostatic tissue level, through their own receptors, by modulating EGF production and/or secretion.

Aged↗
PubMed1992

Lack of linear relationship between hyperinsulinaemia and hyperandrogenism.

OBJECTIVE: Because of continued debate about the role of insulin in the development of hirsutism and in the induction of the polycystic ovary syndrome, we have evaluated the hormonal pattern in a group of hirsute patients. PATIENTS: Fifty-four hirsute patients (age range 18-39 years) of whom 26 patients were obese (O) (BMI 28-53 kg/m2 and W/H greater than 0.85), 12 with ultrasonographic evidence of polycystic ovaries (O PCO) and 14 with normal ovaries. Twenty-eight patients were within normal weight range, and, of these, 14 presented ultrasonographic evidence of polycystic ovaries and 14 had normal ovaries. Two groups of age-matched subjects (obese and normal weight), normally menstruating, without hirsutism or history of endocrinopathies or ultrasonographic evidence of polycystic ovaries, served as controls. MEASUREMENTS: Androstenedione and testosterone were evaluated in all patients by RIA, following ether extraction, DHEAS, LH, FSH and insulin were evaluated directly by RIA. SHBG was evaluated by the concanavalin method. Free testosterone (FT%) was calculated according to the formula FT = 4.038-1.607 log SHBG. Integrated areas under the response curve were calculated for LH and insulin respectively following i.v. administration of GnRH (100 micrograms) or oral administration of glucose (75 g). RESULTS: Results (mean +/- standard deviation) showed comparable values of androstenedione in all groups of obese patients and in obese controls (7.3 +/- 2.6 in patients with polycystic ovaries, 7.1 +/- 2.9 in non-polycystic ovary patients and 7.4 +/- 2.6 nmol/l in obese controls, respectively), regardless of baseline and area insulin, the presence or absence of polycystic ovaries, or hirsutism. SHBG levels showed a similar pattern (24 +/- 10, 23.8 +/- 7.9 and 36 +/- 19 nmol/l) as did the percentage of free testosterone, regardless of the presence or absence of hirsutism. Regression analysis of the insulin and LH values (baseline and area) against the androgens and SHBG plasma levels showed that only LH area correlated positively with testosterone (r = 0.36, P less than 0.03), androstenedione (r = 0.44, P less than 0.02), % free testosterone (r = 0.53, P less than 0.001), testosterone/SHBG ratio (r = 0.39, P less than 0.03) and inversely with SHBG (r = -0.57, P less than 0.001). CONCLUSIONS: These results showed (1) no linear relationship between high levels of insulin, ovarian androgen production or free hormone availability, and (2) make it very doubtful that insulin plays a primary role in polycystic ovarian syndrome or hirsutism.

Adolescent↗
PubMed1991

Cerebrospinal fluid estrone in pseudotumor cerebri: a change in cerebral steroid hormone metabolism?

Estrogen and androgen hormones were studied in the plasma and cerebrospinal fluid (CSF) of five patients affected by pseudotumor cerebri (PTC). Six men and six women without cerebral or endocrine diseases were selected as controls. Androstenedione (A), testosterone (T), 17-hydroxyprogesterone (17OH-P), E1 and E2 were measured in plasma and CSF in baseline conditions and following 1 month prednisone therapy (2 mg/die, per os) using RIA following chromatographic separation on celite microcolumns. Men and women affected by PTC show increased CSF E1 levels and marked decreased CSF A levels, with respect to controls. In plasma, on the contrary, normal values of these parameters were observed in PTC. In normal subjects A/E1 ratio shows the same values in plasma and CSF, suggesting for the two hormones analogous feasibility to cross the blood brain barrier. In PTC patients A/E1 ratio is comparable to controls in plasma, but lower in CSF as a result of decreased A and increased E1 contents. The CSF imbalance between A and E1 attenuates but does not disappear after treatment. No correlation is found between pressure levels and steroid pattern both in baseline condition or after one month of treatment. In conclusion, our results demonstrate that PTC is not only associated with increased CSF E1 levels, as previously suggested, but, above all, with decreased CSF A levels and this hormonal impairement seems to be confined to the CSF compartment and not observed in plasma. These data do not lead to any definitive conclusion about the role of altered CSF estrogen and androgen levels in PTC pathogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Immunolocalization, binding, and biological activity of endothelin in rabbit uterus: effect of ovarian steroids.

Specific immunostaining for endothelin 1 (ET-1) was observed in the endometrium but not myometrium of rabbits. The staining was dramatically affected by subacute treatment with ovarian steroids: epithelial cells were predominantly positive in immature rabbits, whereas, in sex steroid-primed rabbits, ET-1 was mainly localized in the stromal compartment. Binding studies were performed in myometrium of estrogen-treated rabbits using labeled ET-1 and ET-3, the corresponding unlabeled peptides, and sarafotoxin b (SRTX). Mathematical modeling of experimental results indicates that two populations of sites are present in myometrium. One site (R1 = 1 pmol/mg protein) shows approximately the same affinity for ET-1, ET-3, and SRTX [dissociation constant (Kd) 100 pM], whereas the second site (R2 = 10 pmol/mg protein) selectively binds ET-1 (Kd 400 pM). According to binding studies, ET-1 was more potent than SRTX in stimulating uterine contraction "in vitro." The subacute administration of increasing concentrations of 17 beta-estradiol (0.2-200 micrograms/kg for 4 days), but not 17 beta-estradiol (200 micrograms/kg for 4 days) plus progesterone (5 mg/kg for 4 days), stimulates a dose-dependent increase in endothelin receptors in myometrium (half-maximal effective dose = 0.7 micrograms/kg for 4 days). However, estrogen treatment does not affect the concentration of endothelin receptors in myometrial cells in primary culture. Conversely, divalent ions like calcium and magnesium enhance the binding of ET-1 to both uterine membranes and cells. Our results indicate that in rabbit uterus endothelin is present in the endometrium, whereas specific receptors are located in myometrium.

Animals↗
PubMed1990

Antiandrogens: clinical applications.

Antiandrogens, preventing androgen action at target tissue level, are used in the treatment of various androgen-dependent diseases. Pharmacologically these substances have either a steroidal structure, like cyproterone acetate (CPA) and spironolactone (SPL), or a non-steroidal structure, like flutamide (FLU). In women with hyperandrogenism (PCO syndrome, idiopathic hirsutism, acne), clinical benefit may be obtained with CPA, which also displays a progestational activity and an antigonadotropic effect. CPA (25-50 mg/day) is used in combination with ethinyl-estradiol (EE) (20-30 micrograms/day) in reversed sequential regimen. SPL, less effective than CPA may be employed in moderate hirsutism and acne at dosages of 100-200 mg/day. During SPL treatment menstrual irregularities are frequent: in this case an association with oral contraceptives is indicated. SPL + bromocriptine (2.5-5 mg/day) has been experienced with success in PCO syndrome. The pure antiandrogen FLU, inducing progressive increase in LH and testosterone secretion, may be used only in combination with oral contraceptives. In men antiandrogens have been tested in BPH and prostatic carcinoma. In BPH the decrease in nuclear receptors and DHT nuclear content during CPA or FLU may represent the rational base of the medical treatment. An improvement in urinary obstructive manifestation has been observed with CPA alone or associated with tamoxifen (100 mg + 100 mg day). In advanced prostatic carcinoma antiandrogens represent a good alternative to estrogen therapy with less side effects and in combination with surgical or medical castration (LH-RH analogues) achieve a complete androgen blockade. An increase in the percentage of remissions and survival has been reported.

Acne Vulgaris↗
PubMed1990

Effect of hCG or hCG+ treatments in young thalassemic patients with hypogonadotropic hypogonadism.

Hypogonadotropic hypogonadism (HH) is common (40%) in beta-thalassemic patients. Taking into consideration that in HH non-thalassemic patients we obtained good results in pubertal development using hCG treatment (1500 IU every 6 days), 10 HH thalassemic subjects (14 5/12 -17 yr, all with bone age greater than 13 6/12) were treated with the same regimen. In 5 of these patients purified FSH (75 IU every 3 days) was added to hCG in order to evaluate the FSH effect on testosterone (T) response (Group 1 was given hCG alone, Group 2 hCG + FSH: Profasi HP and Metrodin Serono). To evaluate the kinetics of testosterone response, plasma level of T was determined basally and 1, 2, 4 and 6 days after hCG injection. This dynamic study and a clinical examination were carried out at the beginning of treatment and at the 4th and 12th month after. Results obtained in the first group confirmed our previous data from non-thalassemic HH patients: in fact, after 12 months of therapy a stage G2-G3 was reached. In the second group, however, testis size and testosterone secretion were significantly higher than in the first group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Pulsatile secretion of luteinizing hormone in agonadal men before and during testosterone replacement therapy.

UNLABELLED: We have reevaluated the question regarding the pulsatile pattern of LH secretion in agonadal men before and following testosterone replacement therapy. Five normal males were used as a reference group and four agonadal men were studied before and during replacement therapy with testosterone enanthate. All the subjects were sampled every 5 min for 12 h (08:00 to 20:00). Data were analyzed using the statistically based and validated pulse detection program DETECT. The normal subjects showed an LH pulse frequency of 10.2 +/- 1.7 peaks/12 h (mean +/- SEM) and a mean duration of 48.8 +/- 14 min, while in agonadal patients without testosterone replacement the frequency of LH peaks (27.5 +/- 2 peaks/12h) was significantly higher than for normal subjects (p less than 0.05), and the mean duration of peaks was lower than in controls (17.2 +/- 1.2 min; p less than 0.01). Following chronic testosterone enanthate replacement therapy (200 mg im every two weeks) these patients showed an increase in the duration and a significant reduction in the frequency of LH peaks (from 27.5 +/- 2 to 18.2 +/- 2.1 peaks/12 h; p less than 0.01) but pulse frequency remained significantly higher than for normal subjects (p less than 0.01). This finding is independent of the choice of p values for false positive detection rate (p = 0.01 or p = 0.005), but it does depend on sampling frequency and is influenced by large (four-fold) changes in the thresholds for peak detection. Using a "discrete deconvolution" technique we estimated the instantaneous secretory rate (ISR) for the two groups of patients. The results using ISR corroborated the findings obtained using analysis of observed plasma LH measurements. ISR computation also showed that the duration of the secretory events of the gonadotropes is significantly shorter (p less than 0.01) than the one estimated on plasma concentration, both in normal subjects and in agonadal patients before and during testosterone administration. IN CONCLUSION: LH pulse frequency observed in basal conditions in agonadal men was much higher than previously reported in primary testicular failure; during conventional testosterone replacement therapy LH pulse frequency of agonadal men was significantly reduced but still higher (p less than 0.01) than in normal men. This finding is probably related to the subnormal plasma levels of testosterone found in agonadal men during the replacement therapy; the analysis of data using a sampling interval of 10 min gave results similar to previous reports, confirming that the choice of sampling interval can markedly affect the evaluation of frequent LH pulsatile secretion.

Adult↗
PubMed1990

Effects of dihydrotestosterone treatment on adrenal gland function and morphology in adult female guinea-pigs.

The effect of chronic treatment of female guinea-pigs with dihydrotestosterone (DHT) on growth and function of the adrenal gland and, in particular, on the reticular zone is described. Two groups of 6 young adult, female guinea-pigs were treated with DHT (1 mg/kg dissolved in peanut oil and injected s.c.) for 30 and 60 days. Two other groups of animals, treated only with oil, were used as controls. At the end of treatment, animals were killed and adrenal glands were quickly removed. Plasma levels of pregnenolone, dehydroepiandrosterone (DHA) and its sulfate (DHA-S), 17 alpha-hydroxyprogesterone, androstenedione, testosterone, estradiol, 11-deoxycortisol, androstenedione, DHT and 3 alpha-androstanediol were determined by R.I.A. following celite microcolumn chromatography. Animals treated for 30 days showed only elevated DHT and 3 alpha-androstanediol plasma levels, whereas animals treated for 60 days also showed increased values of pregnenolone (251 +/- 62 vs 193 +/- 51 ng/dl; P less than 0.05), DHA-S (12,046 +/- 4110 vs 2780 +/- 888 ng/dl; P less than 0.001) and slightly increased values of DHA (110 +/- 31 vs 86.5 +/- 55.4). In the 30-day-treated animals no histological changes were observed, but in the 60-day-treated group the total size as well as cell volumes of the zona reticularis were significantly increased. Normal estrous cycles were observed in the 30-day-treated animals whereas the 60-day-treated animals showed a progressive acyclicity during the second month of treatment. These results indicate that in guinea-pigs, prolonged treatment with DHT induces a growth of the zona reticularis of the adrenal gland associated with increased levels of 5-ene steroids, particularly DHA-S. The mechanisms inducing these modifications are probably mediated by a DHT effect at the hypothalamic-pituitary level. A direct effect of DHT on the zona reticularis, however, cannot be excluded.

Adrenal Glands↗
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↗