Biomedical subjects

R Volpi

Publications and source records attributed to R Volpi.

At least 55 records · Page 3Linked to original sources

PubMed1997

Age-related decrease in the opioid control of LH secretion during reproductive years in normal women.

UNLABELLED: Our previous studies showed that naloxone is unable to stimulate LH secretion in elderly men, suggesting a loss in the endogenous opioid inhibitory control of LH in senescence. METHODS: In the present study, we examined whether increasing age during the reproductive period in women is associated with alterations in the LH-releasing effect of naloxone. Studies were performed in younger (age 20-28 years, n = 8) and older (age 40-48 years, n = 8) subjects with normal menstrual cycles and normal gonadal steroid levels to avoid the interference of premenopause or menopause on gonadotropin secretion. The LH response to naloxone (4 mg as an i.v. bolus plus 10 mg infused in 2 h) was tested not only in normal conditions, but also after chronic dopaminergic stimulation with bromocriptine (5 mg/day for 7 days), because this treatment has been found able to restore normal LH responses to naloxone in elderly men. All tests were performed on the 22nd day of normal menstrual cycles. RESULTS: Naloxone induced a 100% increase in plasma LH levels in the younger group. In contrast, naloxone enhanced only by 50% LH secretion in the older subjects. When experiments were repeated after bromocriptine treatment, the effect of naloxone did not change in the younger subjects, whereas it was significantly higher in the older group. In the presence of bromocriptine, naloxone-induced LH increment in the older group was indistinguishable from that observed in the younger group. These data suggest that during the reproductive period, increasing age is associated with an impairment in the endogenous opioid control of LH secretion. In addition, age-related dopaminergic alterations independent of circulating gonadal steroid levels appear to underlie the defective endogenous opioid control of LH secretion in normally cycling women.

Adult↗

PubMed1996

Gamma-aminobutyric acid mediation of the inhibitory effect of nitric oxide on the arginine vasopressin and oxytocin responses to insulin-induced hypoglycemia.

Previous studies have demonstrated that the nitric oxide (NO) synthase inhibitor L-NAME exerts positive effects on the arginine vasopressin (AVP) and oxytocin (OT) responses to insulin-induced hypoglycemia, suggesting inhibitory actions of NO. The present study was designed to determine whether a gamma-aminobutyric acid (GABA)ergic pathway is involved in regulation of NO action. AVP and OT secretory patterns during insulin (0.15 IU/kg, i.v.)-tolerance tests (ITT) were examined in seven normal male subjects with (experimental tests) and without (control test) concomitant treatment with L-NAME (40 micrograms/kg injected plus 50 micrograms/kg infused, i.v.), the GABAergic agent sodium valproate (600 mg in three divided doses orally) or the combination of L-NAME and sodium valproate. Insulin-induced hypoglycemia increased by 2-fold (peak vs. baseline) plasma AVP and OT levels. In the presence of L-NAME, plasma AVP and OT levels rose 3-fold in response to hypoglycemia and were significantly higher than those in the control test. Administration of sodium valproate alone changed neither AVP nor OT secretory patterns during ITT. In contrast, sodium valproate abolished the facilitating effect of L-NAME on both AVP and OT responses to hypoglycemia. In the ITT plus L-NAME plus sodium valproate test, plasma AVP and OT levels were not significantly different at any time point from those observed during the control ITT. These data indicate a GABAergic mediation of the inhibitory modulation by NO of the AVP and OT responses to insulin-induced hypoglycemia.

Adult↗

PubMed1996

Unreliability of TRH test but not dexamethasone suppression test as a marker of depression in chronic vasculopathic patients.

Thirteen vasculopathic nondepressed men, admitted to the hospital 2 weeks earlier because of stroke, 10 age- and weight-matched patients with major depression, and 10 age- and weight-matched normal controls were tested with TRH and on different occasion with the dexamethasone (DEX) suppression test (DST). Patients with stroke were tested again with TRH and DST after 1 year. All subjects were euthyroid. A blunted TSH response to TRH was observed in 77% of vasculopathic patients, 64% of depressed patients, and 27% of controls. Some depressed patients showed serum GH or cortisol increments in response to TRH. Nonsuppression to DEX was observed in 45% of depressed patients and 15% of vasculopathics but not in normal controls. These data indicate that, in contrast to cortisol nonsuppression to DEX, blunted TSH response to TRH has poor diagnostic value as a marker for depression after stroke and may merely represent the expression of neuroendocrine dysfunction associated with cerebral vasculopathy.

Aged↗

PubMed1996

Age-dependent decrease in the growth hormone response to growth hormone-releasing hormone in normally cycling women.

OBJECTIVE: To establish possible changes in GH secretion in normally cycling women with increasing age. DESIGN: Controlled clinical study. PATIENTS: Nine younger (18 to 33 years) and nine older (41 to 46 years) healthy women. SETTING: Tests were performed on the 22d day of regular cycles. INTERVENTION: All subjects were tested with GH-releasing hormone (GH-RH) (1 mg/kg body weight), the acetylcholinesterase inhibitor pyridostigmine (120 mg by mouth), the somatostatin inhibitor arginine (30 g infused IV over a 30-minute period) alone, and the combination of GH-RH plus arginine or GH-RH plus pyridostigmine. MAIN OUTCOME MEASURES: Glucose, cortisol, androgens, estrogens, thyroid hormones, and insulin growth-like factor (IGF-I) were measured in basal samples. Serum GH levels were measured in samples taken before and over a 2-hour period after drug administration. RESULTS: All basal hormonal values were similar in younger and older women. Insulin growth like factor-I levels were lower in older women. The GH responses to GH-RH alone, pyridostigmine alone, or the combination were lower in the older than in the younger group and were correlated negatively with age. In contrast, either arginine alone or GH-RH plus arginine produced similar GH responses in the two groups. CONCLUSION: These data indicate that the cholinergic stimulatory regulation of GH release is reduced in the older cycling women. Because acetylcholine inhibits hypothalamic somatostatin release, the reduced cholinergic tone in other subjects may result in an increased somatostatinergic tone. Normalization in older women of the reduced GH response to GH-RH by arginine supports this hypothesis.

Adolescent↗

PubMed1996

Influence of nitric oxide on hypoglycemia--or angiotensin II-stimulated ACTH and GH secretion in normal men.

In order to establish whether nitric oxide (NO) is involved in the regulation of ACTH and/or GH secretion, normal male subjects were treated i.v. with the NO-synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME) (40 micrograms/kg injected plus 50 micrograms/kg infused over 60 min) in basal conditions and/or during stimulation with insulin (0.15 IU/kg body weight in an i.v. bolus) to induce hypoglycemia (ITT) or ASP 1 ILE-5 angiotensin II (ANG II) (increasing doses of 4, 8 and 16 ng/kg/min, each dose for 20 min). The administration of L-NAME neither changed the basal secretion of ACTH and GH nor modified the hormonal responses to ANG II stimulation. Also the GH response during ITT remained unchanged in the presence of L-NAME. In contrast, the ACTH response to hypoglycemia was significantly higher when L-NAME was administered. These data suggest that in normal men NO has a negative effect on ACTH secretion, but not GH secretion, in response to hypoglycemia. Furthermore, our results argue against a role of NO in the control of basal and ANG II-stimulated ACTH and GH secretions.

Adrenocorticotropic Hormone↗

PubMed1996

Different effects of the serotonergic agonists buspirone and sumatriptan on the posterior pituitary hormonal responses to hypoglycemia in humans.

The responses of serum oxytocin (OT) and vasopressin (AVP) to the serotonergic HT1A agonist buspirone (15 mg p.o.) or the HTD1 agonist sumatriptan (6 mg injected subcutaneously) were evaluated in 7 normal men either in basal conditions or during an insulin (0.15 iu/kg as an i.v. bolus) tolerance test (ITT). Neither buspirone nor sumatriptan administration modified the basal secretion of AVP and OT. Stimulation of 5HT-1D receptors with sumatriptan was unable to change neither AVP nor OT response to insulin-induced hypoglycemia. On the other hand, the pretreatment with the 5HT1A agonist buspirone significantly enhanced the OT response during hypoglycemia, without modifying the AVP rise. The results of this study suggest that serotonergic 5HT1A receptors may interact with hypoglycemia in the stimulation of OT, but not AVP secretion.

Adult↗

PubMed1996

Circadian variations in plasma ACTH, cortisol and beta-endorphin levels in normal-weight bulimic women.

In order to establish possible alterations in the secretory patterns of adrenocorticotropic hormone (ACTH), cortisol and/or beta-endorphin in bulimia nervosa, the circadian fluctuations of these hormones were evaluated in blood samples taken at 1-hour intervals over 24 h. Eleven bulimic women with normal body weight and 8 weight- and age-matched normal controls were tested during the follicular phase (days 6-8) of normal menstrual cycles. All women were hospitalized for bulimia or for checkup examinations and were tested 3 days after hospital admission. Both normal and bulimic women showed maximal ACTH, cortisol and beta-endorphin levels at 08.00 h, with minimal ACTH and beta-endorphin levels at midnight and cortisol levels at 02.00 h. The general temporal structure of all hormonal secretions coincided in the two groups. However, whereas all measured ACTH/cortisol levels were quantitatively similar in the two groups, plasma beta-endorphin concentrations were significantly higher in bulimic than in control subjects at all examined time points. The enhancement in the overall 24-hour beta-endorphin secretion suggests the presence of an increased opioid tonus in bulimic women, which might play a role in the pathophysiology of the eating disorder.

Adrenocorticotropic Hormone↗

PubMed1996

Effects of intravenously infused pituitary adenylate cyclase-activating polypeptide on adenohypophyseal Hormone secretion in normal men.

The possible stimulatory effects of an intravenous infusion of increasing amounts of pituitary adenylate cyclase-activating polypeptide (PACAP) on anterior pituitary hormone secretions were evaluated in humans. Successively increasing doses of PACAP-38 (2, 4 and 8 pmol.kg-1.min-1; each dose for 20 min) were infused i.v. in 7 normal male subjects. On a different occasion, the same subjects were tested with vasoactive intestinal peptide (VIP; 4 pmol.kg-1.min-1 for 60 min). Circulating GH, ACTH, PRL, TSH and gonadotropin concentrations were measured before PACAP infusion and every 20 min, just before increasing the infusion dose of PACAP. Blood samples were taken before and every 15 min after the beginning of VIP administration. Serum levels of GH, TSH and gonadotropins did not change during PACAP or VIP infusion. Circulating ACTH and PRL concentrations were not modified by the infusion of the lowest dose of PACAP, whereas they were significantly increased in a dose-response fashion when higher amounts of PACAP were given. PRL, but not ACTH levels were significantly increased by VIP infusion. These data show for the first time in humans that ACTH and PRL secretions from the anterior pituitary gland are stimulated by the systemic administration of PACAP. In addition, since VIP stimulated only PRL secretion, PACAP-induced ACTH release appears to be mediated by specific receptors.

Adult↗

PubMed1996

Inhibition by somatostatin of the growth hormone, but not corticotropin response to angiotensin II in normal men.

The effect of an i.v. infusion of somatostatin (SRIH) (4.1 micrograms/min/180 min) on angiotensin II (ANG II infusion for 60 min of successively increasing doses of 4, 8 and 16 ng/kg/min; each dose for 20 min)-stimulated growth hormone (GH) and corticotropin (ACTH) release was studied in 7 normal men. In addition, 7 additional normal subjects were tested with ANG II alone (as described above), GH-RH (0.1 microgram/kg body weight as an i.v. bolus) alone or the combination of GH-RH and ANG II. The ACTH response to ANG II was not modified by SRIH infusion; in contrast, the GH response to ANG II was significantly reduced by the concomitant treatment with SRIH. On the other hand, the administration of GH-RH together with ANG II produced peak GH levels comparable to the sum of the individual responses to ANG II and GH-RH, given alone. These findings provide evidence that the stimulatory effect of ANG II on GH, but not ACTH secretion, is under the inhibitory control of somatostatin, suggesting an interaction between ANG II and SRIH in regulation of GH secretion.

Adrenocorticotropic Hormone↗

PubMed1995

Effects of intravenously infused pituitary adenylate cyclase-activating polypeptide on arginine vasopressin and oxytocin secretion in man.

In order to establish possible stimulatory effects of increasing plasma concentrations of pituitary adenylate cyclase-activating polypeptide (PACAP) on arginine vasopressin (AVP) and/or oxytocin (OT) secretion, successively increasing doses of PACAP-38 (2, 4 and 8 pmol kg min-1; each dose for 20 min) were infused in seven normal men. Plasma AVP and OT levels were measured before infusion and every 20 min, just before increasing the infusion dose of PACAP. During tests, PACAP infusion did not produce untoward side effects or changes in blood osmolality and/or pressure. Plasma OT levels did not change during PACAP infusion. Plasma AVP concentrations were not modified by infusion of the lowest dose of PACAP, whereas they were significantly increased in a dose-response fashion when higher amounts of PACAP were given. These findings demonstrate for the first time in humans that the systemic administration of PACAP exerts stimulatory effects on AVP, but not OT secretion.

Adult↗

PubMed1995

Mediation by nitric oxide of TRH-, but not metoclopramide-stimulated TSH secretion in humans.

In order to establish whether nitric oxide (NO) participates in the regulation of thyroid stimulating hormone (TSH) secretion in humans, seven normal men were treated with a placebo (normal saline) or the NO synthase inhibitor L-NAME, given at doses (40 micrograms kg-1 injected plus 50 micrograms kg-1 infused i.v.) previously found to be unable to change blood pressure. Experiments were carried out either in basal conditions or during stimulation of TSH secretion with an i.v. injection of 200 micrograms thyrotropin releasing hormone (TRH) or 10 mg of the dopaminergic antagonist metoclopramide (MCP). Administration of L-NAME did not change the basal secretion of TSH or the TSH response to MCP, but significantly reduced the TSH increase induced by TRH. These data fail to provide evidence of NO involvement in regulation of basal TSH secretion. NO also appears to be without effects on the dopaminergic control of TSH secretion. In contrast, the inhibitory effect of L-NAME on TRH-induced TSH secretion suggests the mediation by NO of the TSH-releasing action of TRH.

Adult↗

PubMed1995

Influence of age on the GH response to sumatriptan administration in man.

The present study was undertaken in order to assess the influence of aging on the serotonergic control of GH secretion in humans. For this purpose, 6 mg 5-HT1D-serotonergic receptor agonist sumatriptan (or placebo during control tests) was injected subcutaneously in a group of 9 young (26-40 yr old) and a group of 9 elderly male subjects (64-80 yr old). Sumatriptan-induced plasma GH rise was recorded during the next 2 hours. Plasma ACTH levels were also measured. The administration of the placebo was without effects in all subjects. Sumatriptan induced a striking increase in plasma GH levels in the younger group, whereas it slightly increased GH secretion in the older group (f = 9.59, p < 0.02). Plasma ACTH levels showed a similar physiological decline in all subjects during tests, regardless of sumatriptan treatment. These data show impaired serotonergic stimulatory regulation of GH secretion in elderly subjects.

Adrenocorticotropic Hormone↗

PubMed1995

Effect of substance P on basal and thyrotropin-releasing hormone-stimulated thyrotropin release in humans.

To test the possible effects of intravenous administration of substance P (SP) on basal and thyrotropin-releasing hormone (TRH)-stimulated thyrotropin (TSH) release, SP was infused alone (0.5 or 1.5 pmol/kg-1/min-1 for 60 minutes) or after TRH (20 or 400 micrograms in an intravenous bolus) in 21 normal male subjects (aged 26 to 36 years) and in 18 normal women (aged 25 to 32 years). Women were studied during follicular (day 6 to 8) and luteal (day 21 to 23) phases of following regular menstrual cycles. In addition, plasma cortisol levels during SP infusion were measured. In agreement with previous findings, significant increments in plasma cortisol levels were observed in men and women when the higher (1.5 pmol/kg-1/min-1) but not the lower (0.5 pmol/kg-1/min-1) amount of SP was administered. In contrast, in both men and women basal and TRH (20 or 400 mg)-induced TSH releases were not modified by SP at any tested amount. Results in the follicular and luteal phase were similar. These data suggest that in normal men and women plasma SP is not involved in the control of TSH release, at least not outside the blood-brain barrier.

Adult↗

PubMed1995

Low-dose ovine corticotropin-releasing hormone stimulation test in diabetes mellitus with or without neuropathy.

The function of the hypothalamic-pituitary-adrenal (HPA) axis was evaluated in insulin-dependent diabetics without (group I, n = 10) or with (group II, n = 10) established symptomatic neuropathy and in age- and weight-matched normal controls (n = 11). Since the corticotropin (ACTH)/cortisol response to the minimal-effective dose of corticotropin-releasing hormone ([CRH] 0.03 microgram/kg body weight) represents a useful tool for HPA axis examination, all subjects were tested with the low-dose ovine CRH stimulation test. Experiments started at 8:30 AM, when CRH was injected after two basal blood samples were withdrawn, and lasted 2 hours. Basal serum levels of ACTH were similar in the three groups. Administration of CRH induced a small but significant increase in ACTH levels in all subjects; however, the CRH-induced ACTH increase was significantly higher in normal controls than in diabetic groups I and II. Furthermore, a significantly lower ACTH response was observed in group II than in group I. In contrast, basal and CRH-induced cortisol levels were significantly higher in diabetics than in normal controls. Comparisons between diabetic groups showed that both basal and stimulated cortisol secretion was significantly higher in group II than in group I. When peak ACTH responses to CRH and basal cortisol levels were combined, a significant negative correlation was found (r = .545, P < .02). These data show that even uncomplicated diabetes mellitus is associated with adrenal hyperfunction. Such an alteration is more pronounced in the presence of neuropathy.

Adrenocorticotropic Hormone↗

PubMed1995

Mediation by nitric oxide of LH-RH-stimulated gonadotropin secretions in human subjects.

In order to establish whether nitric-oxide (NO) participates in the regulation of gonadotropin secretion in humans, seven normal men were treated with a placebo (normal saline) or the NO synthase inhibitor L-NAME, given at doses (40 micrograms/kg injected plus 50 micrograms/kg infused i.v.) previously found to be unable to change blood pressure. Experiments were carried out either in basal conditions or during stimulation of gonadotropin secretion with an intravenous injection of 100 micrograms LH-RH. The administration of L-NAME was unable to change the basal secretion of FSH and LH. In contrast, L-NAME significantly reduced both FSH and LH increments induced by LH-RH. These data fail to provide evidence of NO involvement in regulation of basal gonadotropin secretion. In contrast, the inhibitory effect of L-NAME on LH-RH-induced LH and FSH secretion suggests the modulation by NO of the gonadotropin releasing action of LH-RH.

Adult↗

PubMed1995

Case report: finasteride-induced gynecomastia in a 62-year-old man.

The authors describe a case of bilateral (with left prevalence) gynecomastia in a 62-year-old man after finasteride treatment because of benign prostatic hypertrophy. Finasteride is an inhibitor of 5 alpha-reductase, the enzyme responsible for testosterone metabolism to dihydrotestosterone. In this patient, nonspecific endocrine alterations were found, except for a significant decrease in dihydrotestosterone levels. In addition, there were no pathologic conditions affecting other organs or pharmacologic treatments that could be responsible for gynecomastia. Drug withdrawal started a progressive reduction of the lumps until complete their disappearance. It is possible that gynecomastia was caused by alterations of estrogen/androgen ratio because of a finasteride-induced decrease in circulating dihydrotestosterone levels. In this article, the authors confirm finasteride antiandrogenic activity and recommend a close follow-up of long-term treatments with finasteride to find out other possible side effects.

Dihydrotestosterone↗

PubMed1995

Dopaminergic and cholinergic control of arginine-vasopressin secretion in type I diabetic men.

Enhanced cholinergic and dopaminergic controls of anterior pituitary function have been described in insulin-dependent diabetes mellitus (IDDM). In order to verify whether similar neurotransmitter alterations also affect the regulation of posterior pituitary hormone secretion, the arginine-vasopressin (AVP) responses to the dopaminergic agonist apomorphine and in a different occasion to physostigmine, an acetylcholinesterase inhibitor, were evaluated in normal (n = 10) and type I diabetics (n = 16). In addition, a control test with normal saline was performed in all subjects. None of the diabetic patients were affected by neuropathy or other diabetic complications. They were divided into two groups according to the duration of their disease (less than 10 years: group 1, n = 8; more than 10 years: group 2, n = 8). Physostigmine (12.5 micrograms kg-1) was infused intravenously over 10 min; apomorphine (60 micrograms kg-1) was injected subcutaneously. Basal AVP concentrations were similar in all groups and remained constant during the control test. In contrast, both drugs induced significant increments in plasma AVP levels in the normal controls and diabetic subjects. However, physostigmine- and apomorphine-induced AVP increments were twofold higher in diabetics than in control subjects. No significant differences were observed between diabetics of groups 1 and 2. No significant correlations between duration of diabetes and peak AVP responses to physostigmine or apomorphine were found within each group or when all diabetic subjects were considered together. These data indicate enhancement of both dopaminergic and cholinergic stimulatory regulations of AVP secretion in patients with uncomplicated IDDM, regardless of the duration of diabetes.

Acetylcholine↗

PubMed1995

Influence of residual C-peptide secretion on the arginine vasopressin response to hypoglycaemia and metoclopramide in insulin-dependent diabetes.

Arginine vasopressin (AVP) hypersecretion in response to metoclopramide or to insulin-induced hypoglycaemia has been described in type I diabetes mellitus. In the present study, we examined whether residual endogenous insulin secretion may play a role in the control of this abnormal AVP secretory pattern. For this purpose, 21 insulin-dependent diabetic men and 10 age- and weight-matched normal men were tested with MCP (20 mg in an i.v. bolus). On a different occasion, subjects were tested with insulin (0.15 IU kg-1). The diabetic patients were subdivided into C-peptide negative patients (CpN, 11 patients without detectable endogenous pancreatic beta cell activity) (group I) and C-peptide positive patients (CpP, 10 patients with residual endogenous insulin secretion) (group II). Experiments started after optimization of the metabolic status of the diabetic men by 3 days of treatment with continuous subcutaneous insulin infusion. The basal concentrations of AVP were similar in all groups. The administration of MCP induced a striking elevation in plasma AVP levels in the normal controls and in the diabetic subjects of groups I and II. However, the AVP rise was significantly higher in group I and group II than in normal controls. Furthermore, group I diabetics showed higher AVP increments than group II. Insulin induced a similar hypoglycaemic nadir in all subjects at 30 min, even though the diabetic subjects of groups I and II had a delayed recovery in blood glucose levels. The hypoglycaemic pattern was similar in group I and II. Hypoglycaemia induced a striking AVP increase in the normal controls.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗