Search PubMed⌕ Search

Biomedical subjects

A Isidori

Publications and source records attributed to A Isidori.

At least 55 records · Page 3Linked to original sources
PubMed1997

Pituitary adenylate cyclase-activating polypeptide regulates rat Leydig cell function in vitro.

The present study was designed to evaluate the effects of both pituitary adenylate cyclase-activating polypeptide (PACAP)-27 and PACAP-38 on testosterone, cAMP and prostaglandin E2 (PGE2) production by purified rat Leyding cells. Because PACAP-38 shares homology with vasoactive intestinal peptide (VIP), the effects of VIP and both PACAP and VIP receptor antagonists on testicular steroidogenesis were also examined. PACAP-38 potentiated testosterone response to a low effective dose of human chorionic gonadotropin (hCG), while PACAP-27 was without effect. Furthermore, PACAP-38 amplified testosterone response to a wide concentration range of hCG until the submaximal dose. VIP evoked a dose-dependent increase of both basal and hCG-induced testosterone production. PACAP potentiation of steroidogenesis was nullified in the presence of a PACAP antagonist, but was not modified by a VIP antagonist. Moreover, while VIP antagonist blunted testosterone response to VIP, PACAP antagonist was without effect. Increasing concentrations of PACAP-38 evoked a dose-response enhancement of both cAMP and PGE2 production. However, this fatty acid is not involved in PACAP activity, as a prostaglandin blocker indomethacin did not modify the effect of PACAP on steroidogenesis. Taken together these findings: (i) demonstrate that PACAP-38 is able to activate both cAMP- and phosphatidylinositol-dependent mechanisms in Leydig cells; (ii) indicate that the peptide exerts an amplificatory action on testicular steroidogenesis stimulated by hCG and that this activity is receptor-mediated, as it is prevented by a PACAP receptor antagonist; (iii) predict the existence of specific PACAP receptors (type 1 binding sites) on Leydig cells.

Animals↗
PubMed1996

Anxiety-induced failure in erectile response to intracorporeal prostaglandin-E1 in non-organic male impotence: a new diagnostic approach.

Intracavernous injection (ICI) of prostaglandin-E1 (PGE1) is used widely as the first diagnostic test in the study of erectile dysfunction. However, a lack of full erection after a maximal dose is frequent. As well as vascular incompetence, this may be due to stress-induced changes, related to the ICI procedure. The aim of this study was to investigate the influence of emotional disturbances on erectile response to ICI in impotent patients. Initially, 24 young men with non-organic impotence (age 34.6 +/- 1.5 years; mean +/- SEM) were selected and randomized single-blind to pharmacoerection with PGE1 alone (20 micrograms/mL) or a mixture (cocktail) containing 20 micrograms PGE1 plus an alpha-adrenergic receptor blocker, phentolamine (Phe, 0.5 mg/mL). Additional studies were also performed double-blind on 10 men with non-organic impotence (age 37.6 +/- 1.2 years) utilizing higher PGE1 dosages for ICI (25 micrograms/mL alone or in combination with Phe, 0.5 mg/mL). After a 7-day interval, all subjects were crossed-over to receive the alternative treatment. The presence of emotional disturbances was assessed in all patients by the administration of rapid tests (Stai-X1 and Stai-X1r for state-anxiety before and after ICI, respectively; Stai-X2 for trait-anxiety; Zung-test for depression) at the first and at the remaining (Stai-X1 and Stai-X1r) ICI sessions. ICI with 20 and 25 micrograms/mL PGE1 led to a comparable percentage of patients who reported a valid-for-intromission (VFI) erection (63 and 60%, respectively). In contrast, use of the cocktails significantly increased the percentage of subjects with a VFI (87 and 90% of the total number of patients tested, respectively; p < 0.05). Moreover, a strong inverse correlation between state-anxiety scores (Stai-X1) and the erectile response to ICI with 20 and 25 micrograms PGE1 was found (r = -0.69, p < 0.001); such a correlation was not present in patients who underwent ICI with the cocktails. Two cases of prolonged erection occurred (one after 20 micrograms PGE1 and the other after 20 micrograms PGE1 plus Phe) which were reversed promptly by the intracavernous injection of metharaminol. It is concluded that the lack of a full erectile response after ICI with PGE1 can be related to the presence of a high 'state-anxiety' in the patients. In such patients, a VFI erectile response can be induced by the administration of a cocktail test-dose.

Adrenergic alpha-Antagonists↗
PubMed1996

Aspirin inhibition of naloxone-induced luteinizing hormone secretion in man.

It is well known that endogenous opioid peptides exert a tonic inhibitory control on GnRH release, leading to the inhibition of LH secretion, whereas eicosanoids, particularly prostaglandin E2(PGE2), stimulate GnRH output. Furthermore, in vitro studies suggest the existence of an interaction between these two regulatory systems in animals. The present work was designed to evaluate the acute effect of the prostaglandin blocker aspirin on plasma LH response to the opiate antagonist naloxone or GnRH in normal volunteers in a placebo-controlled, single-blind study. To exclude a hypothetical action of aspirin directly at the testis level, plasma testosterone concentrations were monitored during basal sampling after acetylsalicylic acid ingestion, whereas the efficacy of the drug as a prostaglandin blocker was tested by the determination of seminal PGE2 levels. Aspirin pretreatment significantly lowered seminal PGE2 levels (from 86 +/- 5 before to 11 +/- 2 micrograms/mL [corrected] after drug administration; P < 0.001) without affecting testosterone concentrations. Moreover, the drug induced a significant reduction of LH response to naloxone, assessed as the mean integrated area under the curve, from 1666.5 +/- 116 to 1197.5 +/- 98 mUI/mL per min (P < 0.05), whereas it did not influence GnRH-induced LH release. We conclude that the effective cycloxygenase blockade inhibits the stimulatory activity of naloxone on LH release, suggesting that the inhibitory tone of opioids on GnRH secretion may be caused by the block of hypothalamic prostaglandin biosynthesis with consequent inhibition of PGE2-induced GnRH secretion.

Adult↗
PubMed1996

[Azoospermia and genetic mutations: implications for the methods of in vitro fertilization].

Much evidence suggests the fundamental role of the Y chromosome during spermatogenesis. Especially, a gene on the long arm (localized in a portion of the chromosome called Yq11), the AZF (azoospermic factor), is necessary for the achievement and the maintenance of the spermatogenetic process. In fact mutations and deletions in this part of the chromosome inevitably cause severe oligozoospermia or azoospermia. Furthermore other genes on the short arm seem to have a role during spermatogenesis: they are called ZFY (zink finger Y, which encodes a DNA binding protein) and TSPY (expressed in the spermatids nuclei); but the function of these genes is still uncertain, since at this moment no deletions or mutations have been found at this level. Further genes only recently cloned include the CREM (cAMP-responsive element modulator), whose mutation causes azoospermia with a spermatidic arrest in the mouse, and the complex c-kit/Steel-factor. The latter is essential for spermatogonial proliferation and differentiation, so that an alteration at this level can determine spermatogonial arrest or the absence of germinal cells with the presence of Sertoli cells only (Sertoli cells only syndrome). In contrast with AZF, both the CREM gene and c-kit/Steel-factor genes are autosomal (chromosome 10 for the CREM, 4 for c-kit, 1 for Steel-factor, respectively). Several genes may be involved in the spermatogenetic process, but their role, excepting for AZF, is still unclear.

Animals↗
PubMed1995

Arachidonic acid and its metabolites effects on testosterone production by rat Leydig cells.

Arachidonic acid (AA) seems to play an important role in testicular steroidogenesis, although controversial data exist in the literature. In the present study AA induced a dose related increase of testosterone (T) formation and, at the highest dose, stimulated the production of prostaglandin E2 (PGE2), leukotrienes B4 (LTB4) and C4 (LTC4) by purified rat Leydig cells. The contemporary addition of the prostaglandin synthesis blocker, indomethacin (IND), and AA further increased T formation, decreased PGE2 levels and did not modify LTB4 and LTC4 concentrations. The addition of a lipoxygenase inhibitor, nordihydroguaiaretic acid (NDGA, 5 microM), did not influence the stimulatory effect of AA on T and PGE2 formation while it decreased the output of LTB4 and LTC4. When 20 microM NDGA was used in addition to AA the expected reduction of leukotrienes release was observed together with a surprising impairment of T and PGE2 secretion. PGE2 and PGF2 alpha did not modify basal T production but reduced HCG-stimulated T secretion at the 10 nM dose. When 5-12- and 15-HETE were tested an enhancement of basal T formation was observed at the 10nM dose. 5-HETE (10nM) stimulated HCG-induced T production. LTA4, LTB4 and LTE4 did not influence basal T output while LTC4 and LTD4 inhibited it. LTC4 (10nM) induced a decrease of HCG-stimulated T production. These findings suggest that: 1) exogenous AA stimulates T secretion; 2) conversion of AA to cycloxygenated and lipoxygenated metabolites is not required for its steroidogenic effect; 3) cycloxygenated and lipoxygenated compounds play a diverse modulatory role on testicular steroidogenesis.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1993

Endothelin stimulates testosterone secretion by rat Leydig cells.

The present study was designed to evaluate the effects of endothelin (ET) on rat testicular steroidogenesis in vitro and the involvement of prostaglandins (PG) and extracellular calcium in its mechanism of action. To this purpose we examined the effects of ET-1 and ET-3 on basal testosterone secretion, the influence of ET-1 on PGE2 release, the interaction of ET-1 and ET-3 with human chorionic gonadotrophin (hCG) and the interference of indomethacin (an inhibitor of cyclooxygenase) and nifedipine (a calcium-channel blocker) in purified rat Leydig cells. The data indicate that ET-1 and ET-3 stimulate basal and hCG-induced testosterone production although the effects of ET-3 were less marked. In addition, a concomitant release of PGE2 was observed after exposure to ET-1. A synergistic interaction between ET-1 and hCG in stimulating testicular steroidogenesis was revealed. Indomethacin was ineffective in modifying ET-1 evoked testosterone output, while in the presence of nifedipine the stimulatory effect of ET-1 was completely abolished. Since it has been shown by others that ET-1 is produced by rat Sertoli cells and specific binding sites are present in Leydig cells, the results of our study indicate that such a peptide may be regarded as a new paracrine factor able to influence steroidogenesis in Leydig cells. The action of ET-1 requires the activity of voltage-operated Ca2+ channels, while PGE2 activation is not essential for its steroidogenic effect.

Animals↗
PubMed1992

Growth hormone-releasing hormone is produced by rat Leydig cell in culture and acts as a positive regulator of Leydig cell function.

Rat GH-releasing hormone (GHRH), mainly contained in hypothalamic neurons, has also been identified in several extraneural tissues, including the gastrointestinal tract, placenta, ovary, and testis. In the testis, GHRH mRNA is ontogenically regulated, and GHRH immunoreactivity can be observed in interstitial cells and tubules, suggesting an intratesticular role for the peptide. Leydig cells in culture are able to produce hypothalamic releasing hormones, i.e. CRH, which acts as an autocrine negative regulator of Leydig cell function. In this study we investigated whether GHRH is present in Leydig cells and evaluated the role of the peptide in Leydig cell function. Adult Leydig cells in culture produced considerable amounts of immunoreactive GHRH [23.9 +/- 2.1 (+/- SE) pg/10(6) cells.30 min], and the release of the peptide was acutely stimulated by hCG. HPLC analysis of GHRH in media from basal and hCG-treated cultures showed the presence of a single peak eluting at the same retention time as that of hypothalamic rat GHRH. Radioligand binding and activation studies revealed a common receptor for vasoactive intestinal peptide (VIP) and rat GHRH in Leydig cell membrane. Specific binding of [125I]VIP to Leydig cell membranes showed the presence of a single site, with high affinity and low binding capacity. The relative potencies of VIP-related peptides for inhibition of radioligand binding were: VIP > rat GHRH > secretin > human GHRH. In cultured Leydig cells, GHRH and VIP stimulated cAMP production, consistent with coupling of the receptor to the adenylate cyclase system. VIP displayed a lower ED50 than GHRH in stimulating cAMP production (P < 0.01), comparable with the higher binding potency of this peptide. No additive effects of VIP- and GHRH-stimulated cAMP generation were observed, suggesting that both peptides compete for the same receptor protein. GHRH and VIP had no effect on basal steroidogenesis, indicating a lack of tonic actions and compartmentalization of the peptides' effect. On the other hand, GHRH acted as a potentiator of the acute gonadotropin stimulation of testosterone production and cAMP generation. [125I]hCG binding to the Leydig cells in culture showed that GHRH was unable to affect the number or affinity of binding sites for hCG, indicating that the GHRH-sensitizing effect on LH action is beyond the level of gonadotropin binding and possibly is through the facilitation of LH receptor coupling functions.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Transperineal vesiculodeferentography under ultrasound control: first experiences.

Vesiculodeferentography (VDG) plays an important role in diagnosing male infertility and staging of prostatic cancer; the techniques of performing the examination are, today, well codified: 1) retrograde, by endoscopic cannulation of ejaculatory ducts; 2) anterograde, by cannulation of the deferent duct surgically prepared at the scrotum. In order to avoid the difficulties of the first method and the risks in the second (like stenosis and fibrosis of the deferent duct) we propose a new simple and safe method based on the direct transperineal puncture of the seminal vesicle under direct echographic control with a transrectal probe. We have studied 16 patients, mainly in order to stage prostatic cancer; the procedure was easy to perform, well tolerated and without consequences at seminal level. It required only 30 minutes, without anaesthesia and with a very low cost. The method permits a clear visualisation of anatomical structures and of possible pathologies with particular reference to vesicular invasion by a prostatic cancer.

Catheterization↗
PubMed1989

Immunoreactive beta-endorphin levels in cerebrospinal fluid of children with acute lymphoblastic leukemia: relationship with glucocorticoid therapy and neurological complications.

Neurological disorders, such as seizures, are not infrequently associated with anti-leukemic therapy. It has been hypothesized that a disrupted peptidergic transmission between neurons could be the cellular basis of the neurological dysfunction. Since endogenous opioids have been recently found to alter neuronal function and possess anticonvulsant properties, the cerebrospinal fluid (CSF) immunoreactive beta-endorphin levels in children with Acute Lymphoblastic Leukemia (ALL) during chemotherapy and cranial irradiation have been studied. Twenty-seven children, 2 at low, 20 at medium and 5 with high risk ALL, undergoing prophylactic treatment for meningeal leukemia, entered the study. Sequential lumbar punctures with introduction of MTX combined with oral prednisone therapy were performed; each lumbar puncture sample was collected and assayed for immunoreactive beta-endorphin. All the patients studied showed a biphasic profile of the peptide with the minimum levels reached during the induction (days 14-28) and the maximum levels detected at the end of the intensification chemotherapy (days 49-55). In the 3 groups the beta-endorphin decrease corresponded to the period of prednisone therapy; the increase was concomitant with the suspension of oral glucocorticoids. 3 patients showed tonic-clonic seizures which coincided with the lowest cerebrospinal fluid beta-endorphin levels and, in the follow-up, 13 out of 27 patients displayed EEG abnormalities. From these findings a relationship between cerebrospinal fluid beta-endorphin concentrations and neuronal excitability in patients with ALL can be suggested. It is also evidenced that oral glucocorticoid therapy has profound inhibitory effects on central beta-endorphin levels.

Adolescent↗
PubMed1989

Neuroendocrine control of male reproductive function. The opioid system as a model of control at multiple sites.

It is known that the same peptide can be identified in different secretory tissues and in the central nervous system (CNS). We now provide evidence that the same peptides can be found in different organs related to the control of a single function, and speculate on the possibility that this reflects a common neuroendocrine programming. Endogenous opioid peptides (EOP) inhibit the reproductive function acting via the CNS. EOP inhibit gonadotropin secretion in rodents and humans via inhibition of GnRH release and have direct inhibitory actions at the pituitary level via specific binding sites on the gonadotrophs. However, EOP can also be synthesized in the testis and in different compartments of the male genital tract. Several findings indicate that EOP of the reproductive tract have a local, paracrine role. These include: (1) the detection of significant beta-endorphin (beta-EP) production by rat Leydig cells (Lc) in cultures; (2) the hormonal regulation of Lc beta-EP production by positive (gonadotropins) and negative (steroids, glucocorticoids, GnRH) factors; (3) the presence of opioid binding sites (Kd in the nanomolar range) in tubular homogenates and Sertoli cells (Sc) in culture of adult and immature rat testes; (4) the inhibition of basal and FSH-stimulated ABP production by Sc in culture when chronically exposed to beta-EP treatment; (5) the detection of high levels of beta-EP and met-enkephalin in human semen with values 6-12 times higher than in plasma; (6) the evidence for inhibitory functions of seminal opioids on sperm motility, vas deferens muscle contraction and partner immune system. Thus the same peptides, i.e. EOP, may control the reproductive function at multiple sites, operating as a multimessenger system in which the central and peripheral level are unified by the common chemical and inhibitory nature of the message.

Animals↗
PubMed1989

Endorphins in male impotence: evidence for naltrexone stimulation of erectile activity in patient therapy.

In the present study we evaluated whether naltrexone administration could stimulate sexual function in 30 male patients, ages 25 to 50 years, with idiopathic impotence of at least one year's duration and not of organic etiology. The patients received naltrexone (50 mg/day) or placebo, on a random basis for two weeks. Sexual performance, expressed as the number of full coitus/week, was assessed before (time 0) and during (on days 7 and 15) each treatment. The naltrexone therapy significantly increased the number of successful coitus compared to placebo after 7 and 15 days of treatment: improvement of sexual performance was evident in 11 out of the 15 treated patients. All the patients experienced a significant increase in morning and spontaneous full penile erections/week. No significant side effects were reported. Endocrine studies revealed no significant modification of plasma LH, FSH or testosterone by naltrexone, suggesting that the positive effect of the drug on sexual behavior was exerted at a central level. A two-month follow-up, at which time patients were off treatment, erectile capacity had returned to baseline in 10 patients, while five reported complete recovery of their sexual ability. We hypothesize that an alteration in central opioid tone is present in idiopathic impotence and is involved in the impairment of sexual behavior.

Adult↗
PubMed1989

Identification of immunoreactive gastrin-releasing peptide related substances in adult rat Leydig cells.

Purified adult rat Leydig cells were found to produce gastrin-releasing peptide (GRP) by radioimmunoassay (RIA). Gel chromatography of the extracted material showed a single peak of GRP immunoreactivity. Further high pressure liquid chromatography (HPLC) analysis resolved the extract into two peaks that closely resembled the C-terminal fragment of GRP, GRP18-27 and GRP14-27. Immunohistochemical studies revealed specific staining for GRP in the Leydig cells of adult rat testis. These results demonstrate, by a number of independent criteria, that rat Leydig cells contain substances which behave like authentic GRP-like peptides. Since the peptides appear to be of local origin, a paracrine function within the rat testis is suggested.

Animals↗
PubMed1989

Isolation of a human seminal plasma peptide with bombesin-like activity.

Bombesin (BN) and BN-like peptides such as gastrin-releasing peptide (GRP) belong to the growing group of regulatory peptides. Bombesin and GRP share the same carboxyl-terminal heptapeptide sequence that is essential for receptor recognition and biologic activity. Immunohistochemical findings have indicated the presence of a BN-like peptide in the neuroendocrine cells of the human prostate. These findings, together with the high concentrations of different regulatory peptides recently found in seminal plasma, prompted us to characterize a BN-like peptide in human semen by gel-filtration chromatography, reverse-phase high-pressure liquid chromatography, and in vitro bioassay. Here we demonstrate that human semen contains high levels (mean +/- standard deviation, 288.9 +/- 114.39 pg/ml) of a substance that closely resembles the 14-27 carboxyl-terminal fragment of GRP (GRP 14-27). The partially purified peptide obtained from this source, examined on an in vitro bioassay that is especially useful for testing BN-like activities, elicits a contractile response of the rat uterus that is indistinguishable from that stimulated by standard BN and GRP 14-27. The GRP 14-27 present in human seminal plasma may be involved in some aspect of the process of fertilization.

Adult↗
PubMed1988

Immunobiology of male infertility.

Experimental and clinical data reported in the literature emphasize the important role that immune factors may play in the genesis of male infertility even if many problems still remain to be solved. Auto or homo-sensitization in animals (and in male volunteers) can be obtained with testicular homogenate or epididymal spermatozoa and complete Freund's adjuvant. Immune orchitis in spontaneous human pathology has also been reported. Vasectomy for the voluntary control of male fertility may be considered a particular form of experimental autoimmunization; and many vasectomized individuals develop antisperm antibodies in blood serum and/or in seminal plasma. In spontaneous male infertility antisperm antibodies can: (i) be a mere epiphenomenon; (ii) be a factor aggravating a pathologic situation already able to cause infertility; (iii) play a pathogenetic role in some forms of so-called idiopathic infertility and so could be defined as infertility due to antisperm antibodies. If the antisperm autoimmune reaction represents the casual factor of infertility, corticosteroid therapy seems to give the most satisfactory results, administered either in high doses for a very short time period or in low doses over a prolonged period, or even after transient pharmacologically induced azoospermia.

Autoantibodies↗
PubMed1988

Low serum bioactive luteinizing hormone in nonorganic male impotence: possible relationship with altered gonadotropin-releasing hormone pulsatility.

We determined the biological activity of serum LH in 23 men, aged 25-50 yr, complaining of nonorganic impotence of at least 1-yr duration and 20 normal men. All of the impotent men had normal general physical examinations, penile Doppler tests, psychological tests, and peripheral nerve conduction. Serum PRL, FSH, LH, and thyroid hormone concentrations were normal as were the results of provocative tests of TSH, gonadotropin, and PRL secretion. The mean serum immunoreactive LH (I-LH) levels, measured in each impotent and normal man in three samples taken at 15-min intervals, were similar [7.2 +/- 0.5 (+/-SE) vs. 6.4 +/- 0.5 mIU/mL (IU/L)]. In contrast, the mean serum bioactive LH (B-LH) level was significantly lower in the impotent men than in the normal men [15.9 +/- 2.1 (+/-SE) vs. 33.0 +/- 2.8 mIU/mL (IU/L); P less than 0.05], as was the LH bio- to immunoactive (B/I) ratio (2.1 +/- 0.2 vs. 5.6 +/- 0.5; P less than 0.02). The mean serum testosterone level in the impotent men, although all individual values were within the range of normal for our laboratory [200-900 ng/100 mL (693-3120 nmol/L)], was 25% lower than that in the normal men [347 +/- 23 vs. 450 +/- 26 ng/100 mL; P less than 0.05 (1204 +/- 81 vs. 1560 +/- 91 nmol/L)]. In addition, a significant positive correlation was found between serum testosterone levels and LH B/I ratios in the impotent men (r = 0.45; P = 0.029). Pulsatile LH secretion, measured in six impotent and four normal men in blood samples collected every 15 min for 6 h, was similar in the two groups. The mean serum I-LH levels were similar [7.5 +/- 1.1 (+/-SE) vs. 5.1 +/- 1.0 mIU/mL (IU/L)], while the mean serum B-LH level as well as the LH B/I ratio was significantly lower in the impotent men throughout the observation period [11.4 +/- 2.0 (+/-SE) vs. 26.0 +/- 3.2 mIU/mL (IU/L) and 1.4 +/- 0.2 vs. 5.4 +/- 0.6; P less than 0.05 and P less than 0.02, respectively]. The B-LH pulse amplitude in the impotent men was reduced [mean peak LH, 8.6 +/- 0.3 vs. 25.3 +/- 4.0 mIU/mL (IU/L); P less than 0.05], while the LH pulse frequency was similar in the two groups. The median intrapulse LH B/I ratios were significantly higher than the median interpulse ratios in both impotent (P = 0.02) and normal men (P = 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗