Insulin-like growth factor-I and -II in human benign prostatic hyperplasia: relationship with binding proteins 2 and 3 and androgens.

In prostatic tissue, androgen action may be mediated by growth factors such as insulin-like growth factor-I (IGF-I) and II (IGF-II), which are mitogenic for prostatic cells and modulate the stroma-epithelium interaction. IGF-binding proteins (IGFBPs) have an autocrine and/or paracrine role in regulating the local actions of the IGFs. In this study, testosterone, dihydrotestosterone (DHT), 3 alpha androstanediol (3 alpha diol), IGF-I, IGF-II, IGFBP2, and IGFBP3 concentrations were evaluated in human benign prostatic hyperplasia (BPH) tissue. Samples of prostate tissue were removed by suprapubic prostatectomy from twelve BPH patients. Androgen tissue levels were determined by radioimmunoassay after purification on celite microcolumns. IGF-I, IGFBP2, and IGFBP3 were measured by radioimmunoassay, and IGF-II by immunoradio metric assay, after acidification and chromatography on Sep-pak C18 Cartridges for IGF-I and IGF-II. Androgen concentrations, expressed in ng/g tissue (mean +/- SE), were 0.51 +/- 0.05 for testosterone, 5.3 +/- 0.16 for DHT, and 1.1 +/- 0.07 for 3 alpha diol. IGF-I, IGF-II, IGFBP2, and IGFBP3 levels were 24 +/- 3.7, 121 +/- 14 ng/g tissue and 0.44 +/- 0.05 and 1.2 +/- 0.17 micrograms/g tissue, respectively. No correlation between IGF-I, androgens, and IGFBPs was found. IGF-II was positively correlated with DHT (r = 0.78; p = 0.003) and 3 alpha diol (r = 0.66; p = 0.021) but not with IGFBPs. These data suggest that in BPH, DHT modulates the IGF system by increasing IGF-II without modifying IGFBPs. Therefore, the stroma-epithelium interaction, which plays an important role in prostatic growth, may be regulated by DHT through IGF-II.

[Changes in growth hormone/insulin-like growth factor-1 axis in patients with normal pituitary function and biventricular cardiac failure and hepatic stasis]. / Alterazione dell'asse ormone della crescita/insulin-like growth factor-1 in pazienti normopituitarici con scompenso cardiaco biventricolare e stasi epatica.

Previous studies showed increased growth hormone (GH) plasma levels in patients with severe heart failure. It has been hypothesized that the activation of adenohypophysis determines the enhanced release of GH. The present study was designed to verify whether impaired hepatic function, due to biventricular cardiac failure and hepatic stasis, by reducing synthesis and release of insulin-like growth factor-1 (IGF-1), may affect the negative feedback mechanism of the IGF-1 on GH secretion. We studied 20 normotensive, non diabetic patients without primitive liver disease; 10 patients in NYHA functional class IV with clinical signs of biventricular cardiac impairment and hepatic stasis (Group A); 10 patients in NYHA functional class III with prevalent left ventricular dysfunction (Group B). Blood samples for radioimmunologic determination of GH, IGF-1, atrial natriuretic factor (ANF), proteins, albumin plasma levels and transaminase plasma levels measurements, were collected 24 hours before hemodynamic study. Group A patients had clinical and hemodynamic signs of hepatic stasis with impaired liver function (SGOT 68 +/- 5.5 U/l; SGPT 89 +/- 4.3 U/1; proteins 4.56 +/- 0.4 g/dl with albumin/globulin ratio < 1; albumin plasma levels 2.8 +/- 0.7 g/dl). The parameters were normal in Group B (SGOT 16 +/- 3.7 U/l;SGPT 13 +/- 1.9 U/l; proteins 7.5 +/- 0.7 g/dl with albumin/globulin ratio > or = 1.5;albumin plasma levels 4.2 +/- 1.2 g/dl). ANF values, over normal range in both groups, were significantly higher in Group A (157.9 +/- 43.9 vs 65.6 +/- 14.6 fmol/ml.p < 0.0001). In Group A GH values were increased (4.9 +/- 4.5 vs 0.12 +/- 0.04 ng/ml); on the contrary IGF-1 values were lower (187.9 +/- 98.2 vs 260.4 +/- 141.4 ng/ml, p < 0.01). The comparison between IGF-1 and albumin plasma levels showed a high correlation either in Group A (r = 0.88, p < 0.001;) or in Group B (r = 0.81, p < 0.001). Our findings allow to hypothesize that the reduced hepatic synthesis and release of IGF-1 may be responsible for the lack of trophic action of GH on cardiac myocytes in patients with biventricular heart failure and hepatic stasis.

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)

[The acute and 24-hour modifications to the atrial natriuretic factor in patients who have undergone mitral valvuloplasty. The hemodynamic and echocardiographic correlations]. / Modificazioni acute ed a 24 ore del fattore natriuretico atriale in pazienti sottoposti a valvuloplastica mitralica. Correlazioni emodinamiche ed ecocardiografiche.

BACKGROUND: The recent introduction of percutaneous transvenous mitral valvuloplasty (PTMV) for the treatment of mitral stenosis (MS) has provided a unique human model for the study of short-term changes in ANF secretion before and after a reduction in left atrial pressure. This study was designed to investigate the effect of a short-term reduction in left atrial pressure and volume, as determined by echocardiographic study, on ANF and other neurohumoral factor plasma levels (renin and aldosterone). MATERIALS AND METHODS: 10 patients in III FC NYHA, with normal sinus rhythm and MS underwent PTMV. Hemodynamic parameters were measured immediately before and after (20-30 minutes) PTMV. Plasma levels of ANF, aldosterone and plasma renin activity (PRA) were obtained before (24 h) and after (2 h and 24 h) valvuloplasty; echocardiographic left atrial size before (24 h) and 24 h after PTMV. RESULTS: Immediately after PTMV mean left atrial (LA) pressure decreased from 22.3 +/- 6.8 mmHg to 10.0 +/- 2.4 mmHg (p < 0.01); mitral valve area (MVA) increased from 0.99 +/- 0.28 cm2 to 2.17 +/- 0.26 cm2 (p < 0.01). 24 hours after PTMV on echocardiography, LA systolic volume decreased from 59.5 +/- 16.9 cm3 to 42.3 +/- 8.3 cm3 (p < 0.01), LA diastolic volume from 82.6 +/- 15.8 cm3 to 66.5 +/- 12.6 cm3 (p < 0.01), and LA diameter from 48.1 +/- 7.5 mm to 39.2 +/- 4.4 mm (p < 0.01). ANF plasma levels before PTMV were 64.0 +/- 36.9 fmol/ml; 2 and 24 hours after PTMV they fell to 34.2 +/- 21.6 fmol/ml (p < 0.01) and to 20.3 +/- 21.0 fmol/ml (p < 0.01), respectively. PRA values were 15.7 +/- 13.2 ng/ml/h before PTMV; 2 and 24 hours after PTMV they increased to 17.5 +/- 23.2 ng/ml/h (NS) and to 22.3 +/- 16.8 ng/ml/h (p < 0.01). The aldosterone plasma levels were 43.2 +/- 27.9 ng/dl before PTMV and 47.3 +/- 35.8 ng/dl (NS) and 45.3 +/- 28.0 ng/dl (NS) 2 and 24 hours after PTMV. CONCLUSIONS: These results indicate that LA "de-stretching" due to the MVA increase and LA pressure decrease, leads to an abrupt reduction of ANF secretion. According to other studies, PRA increases immediately after PTMV, with a further increase 24 hours after PTMV.

Identification and localization of atrial natriuretic factor receptors in human spermatozoa.

Specific binding sites for atrial natriuretic factor (ANF) have been detected and localized in viable human spermatozoa through radioreceptor analysis and autoradiography, respectively. Radiotracer uptake was time and concentration dependent. Scatchard analysis of saturation data showed a single class of ANF receptors with a kd of 2.5 nM and a Bmax of 1.03 fmol/10(6) sperm 2.5 min-1, corresponding to about 620 molecules per sperm. Nonreducing SDS-PAGE analysis after covalent cross-linking of sperm bound 125I-ANF evidenced a single displaceable (i.e., specific) band with an apparent molecular weight of 135-140kD. In 125I-ANF bound spermatozoa, optical autoradiography showed an exclusive distribution of silver grains covering the midpiece region. The effects of ANF binding on ionic homeostasis and cyclic nucleotide metabolism, which modulate a number of sperm cellular processes, could make this factor play outstanding roles in gamete physiology.

Plasma 19-hydroxy-androstenedione (19-OH-A) in essential hypertension.

19-hydroxy-androstenedione (19-OH-A), a C19 steroid, is an amplifier of the sodium retaining action of aldosterone under the control of ACTH and renin-angiotensin system. These findings suggest that 19-OH-A may be involved in the regulation of hydroelectrolyte balance and blood pressure. Aim of the present study was to examine the behaviour of 19-OH-A in normal volunteers (N) and in patients with Essential Hypertension (EH) in basal conditions and after dynamic tests such as postural changes, physical exercise and ACTH administration. The significant increase in 19-OH-A after ACTH confirms its adrenal origin. During bicycle exercise the significant increase in plasma catecholamines, renin-activity, aldosterone, blood pressure and heart rate at maximum effort was not associated with a parallel increase in 19-OH-A. No significant differences were found in plasma 19-OH-A levels between N and EH patients both in basal conditions and after dynamic tests. Therefore, our findings seem to exclude an important role of 19-OH-A in the pathogenesis of EH.

Plasma catecholamine responses during a personalized physical stress as a dynamic characterization of essential hypertension.

High performance liquid chromatography (HPLC) with electrochemical detection proves to be a reliable method for determination of plasma catecholamines (CA) to assess the possible role of the sympathetic nervous system (SNS) in essential hypertension (EH). The present investigation in a group of 15 normotensive (N) and 13 stable EH patients, homogeneous for age and duration of hypertension, was carried out without treatment in the supine position, up-right position and during a personalized bicycle exercise. Mean blood pressure, mean heart rate, plasma renin activity and plasma aldosterone were also evaluated at the various exertion phases. Norepinephrine (NE) and epinephrine (E) showed a progressive increase in N and in EH patients, reaching the highest values at maximum effort. However, EH patients showed higher E plasma levels than N before maximum effort. Dopamine (DA) reached the highest values in N at maximum effort and in EH patients at recovery time. These findings allow us to foresee the possibility of a better characterization of the SNS role in EH.

Intramuscular and subcutaneous administration of atrial natriuretic factor in the rat.

The effects of ANF (99-126) and its active analog, [3-mercaptopropionic 105]-ANF (105-126), on diuresis and natriuresis were assessed in the rat after intramuscular (i.m.) or subcutaneous (s.c.) injection. Water and sodium excretion increased significantly after i.m. or s.c. administration of either peptide in the first 20-min urine collection. ANF (99-126) was more active i.m. than its analog, while they both produced similar diuresis and natriuresis when they were administered s.c. The rapid and significant increase of plasma IR-ANF levels, detected by radioimmunoassay and analyzed by high performance liquid chromatography after i.m. or s.c. injection of these peptides, indicates very rapid passage into the blood circulation without degradation. These data demonstrate that either the i.m. or s.c. route can be used to administer ANF or its analog.

[Hormonal and psychophysiologic responses under conditions of experimental stress in subjects with essential arterial hypertension]. / Risposte ormonali e psicofisiologiche in condizioni di stress sperimentale in soggetti con ipertensione arteriosa essenziale.

Two sex balanced groups of 6 subjects each (hypertensive patients vs normotensive subjects) were monitored for both biochemical and psychophysiological variables under stress (PRA, Adrenal Corticosteroid, Aldosterone, HR and Blood Pressure). A computed controlled RT procedure was employed as stress stimulation. The results suggest that different coping mechanisms are present in hypertensives and normotensives. Hypertensives were more emotionally involved and less efficient in stimulus habituation. Biochemical mechanisms have been hypothesized to explain these differences.

[Clinical study of the efficacy of oral potassium canrenoate and spironolactone in essential arterial hypertension]. / Studio clinico sull'efficacia del canrenoato di potassio orale e dello spironolattone nell'ipertensione arteriosa essenziale.

A group of 13 male and 8 female out-patients (mean age: 40.57 years), with primary arterial hypertension, was submitted to two periods of treatment in a cross-over study with spironolactone and potassium canrenoate. Each preparation was given at the dose of 200 mg/day per os for 21 days, with a 10-day interval between treatments. Both preparations proved active on the systolic and diastolic pressure values controlled 7 days. However, potassium canrenoate showed a greater and more rapid effect, particularly on diastolic arterial pressure, as also demonstrated by the statistical analyses. PRA and aldosteronemia increased with both treatments, but this increase resulted significantly lower with potassium canrenoate. The minor stimulating action on the renin-angiotensin-aldosterone mechanism by potassium canrenoate may be the reason for its greater anti-hypertensive effect. Both treatments were perfectly tolerated locally and systemically.

[Behavior of aldosterone and plasma renin activity after ACTH administration and insulin-induced hypoglycemia in patients with essential arterial hypertension]. / Comportamento dell'aldosterone e dell'attività reninica plasmatica dopo ACTH e ipoglicemia insulinica in pazienti con ipertensione arteriosa essenziale.

The response of plasma aldosterone (PA) and plasma renin activity (PRA) to ACTH stimulation (0.25 mg Tetracosactide infusion/10 h) and to insulin-induced hypoglycemia (0.1 U/kg b.w.) has been studied in 34 essential hypertensive (EH) patients. Corticotrophin stimulation increases significantly PA, the percent increase being higher in normal PRA EH patients than in controls but comparable to controls in low PRA EH patients. PRA shows a slight and transient elevation. A significant increase in PA is observed also during the insulin test, but the percent increase is lower than that under ACTH stimulation. The possibility that aldosterone is involved, under severe and frequent stress, in the genesis of essential hypertension is discussed.

18-hydroxy-11-deoxycorticosterone response to ACTH, insulin and furosemide administration in essential hypertensive patients.

Investigations were carried out on the behavior of 18-hydroxy-11-deoxycorticosterone (18-OH-DOC) in essential hypertension (EH) under exogenous administration of synthetic ACTH and insulin. 40 stable EH patients and 21 normal subjects were included in the study. The increase (12-fold basal values) in plasma 18-OH-DOC in normal subjects under Tetracosactide was significantly higher than cortisol (4-fold basal values). Furthermore, insulin hypoglycemia increased 18-OH-DOC levels 5-fold, whilst basal values of cortisol were increased 2-fold. An increase in 18-OH-DOC and cortisol was also observed in EH patients: in the subgroup with normal and low plasma renin activity, however, the rise in these two steroids was significantly lower than in normal subjects both under Tetracosactide and insulin. No significant hormonal modifications were observed after furosemide administration either in the normal subjects or in the EH patients. 18-OH-DOC by itself does not, therefore, appear to play a pathogenetic role in EH.

18-Hydroxy-11-deoxycorticosterone in hypertensive uremic patients during hemodialysis.

The present study was carried out in 25 hypertensive uremic patients on regular 4 h dialysis, 3 times a week. Plasma 18-hydroxy-11-deoxycorticosterone (18-OH-DOC), aldosterone (PA) and corticosteroids were determined by radioimmunoassay and competitive protein binding technique before and at the end of the 1st, 2nd and 3rd hour of hemodialysis. Plasma 18-HD-DOC was normal before dialysis and did not change significantly during hemodialysis, whereas body fluids and electolytes decreased progressively. No correlation was observed between blood pressure and 18-OH-DOC during dialysis. 18-OH-DOC did not correlate with PA which decreases progressively during hemodialysis and was correlated to plasma corticosteroids only at the 3rd hour of dialysis, probably on account of the enhanced influence of ACTH on the adrenal cortex.