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Biomedical subjects

P Filipponi

Publications and source records attributed to P Filipponi.

At least 55 records · Page 3Linked to original sources
PubMed1984

Catecholamines and pituitary function. 2. Prolactin response to different dopamine doses in normal cycling women and patients with prolactin-secreting pituitary tumors, both before and after endogenous catecholamine synthesis inhibition.

The inhibitory effect of various doses of dopamine on serum PRL levels was assessed in both normal cycling women and patients with tumoral hyperprolactinemia before and after endogenous catecholamine synthesis inhibition by alpha-methyl-p-tyrosine, a strong and specific tyrosine-hydroxylase inhibitor. Dopamine infusion induced a significant decrease in the serum PRL levels in both normal cycling and hyperprolactinemic subjects. The mean percent inhibition of baseline PRL induced by the various dopamine infusion rates (0.1, 0.5, 1.0 and 2.0 micrograms/kg/min) was similar in regularly cycling women and in patients with tumoral hyperprolactinemia both before and after endogenous catecholamine synthesis inhibition by alpha-methyl-p-tyrosine. Alpha-methyl-p-tyrosine pretreatment significantly increased serum PRL concentrations in normal women and enhanced their responsiveness to the exogenously administered dopamine. Hyperprolactinemic patients, on the contrary, did not show any significant variation in either basal PRL release or the PRL sensitivity to dopamine infusion after endogenous catecholamine synthesis inhibition. These data indicate that reduced dopamine delivery to the adenomatous lactotroph, either due to a primary hypothalamic abnormality or to a deranged vascular pituitary arrangement, rather than a reduced PRL sensitivity to dopamine inhibition, is the main event accounting for PRL hypersecretion in women with PRL-secreting pituitary tumors.

Catecholamines↗
PubMed1984

Catecholamines and pituitary function. I. Effects of catecholamine synthesis inhibition and subsequent catecholamine infusion on gonadotropin and prolactin serum levels in normal cycling women and in women with hyperprolactinemic amenorrhea.

To investigate the role of catecholamines in the control of gonadotropin and prolactin release, we examined the effects of a catecholamine synthesis inhibitor (alpha-methyl-p-tyrosine, AMPT) administration and those of dopamine (DA) or epinephrine (EPI) infusion after endogenous catecholamine synthesis inhibition, on FSH, LH and PRL serum levels, in regularly cycling women and in patients with hyperprolactinemic amenorrhea. AMPT administration was followed by a prompt increase in serum PRL in regularly cycling women, but not in women with hyperprolactinemia either due to a PRL-secreting pituitary microadenoma or 'idiopathic'. Gonadotropin serum levels did not show any significant variation after AMPT in both normal and hyperprolactinemic women. DA infusion after endogenous catecholamine synthesis inhibition by AMPT, induced an appreciable decline in PRL levels in both normal and hyperprolactinemic subjects. Although the net decrements were higher in the hyperprolactinemic group, the PRL fall was similar in the two groups when expressed as a percentage of preinfusion PRL concentrations. LH serum levels similarly fell during DA infusion in normal women and in hyperprolactinemic patients, while FSH concentrations did not show any significant change. EPI infusion after analogous AMPT pretreatment was followed by an evident decrease in serum PRL in both normal and hyperprolactinemic subjects. No significant changes in FSH and LH serum concentrations were observed during EPI administration. These data, while confirming the existence of a functional derangement in the neural inhibitory control of PRL secretion in hyperprolactinemia either due to a PRL-secreting pituitary microadenoma or so-called 'idiopathic', do not agree with the hypothesis that tubero-infundibular DA hyperactivity inhibits gonadotropin secretion in hyperprolactinemic patients. The inhibitory action of exogenously administered DA might represent rather a pharmacological effect than express a physiological inhibitory role of hypothalamic DA pathway on gonadotropin secretion in humans.

Adult↗
PubMed1984

Catecholamines and pituitary function. III. Restoration of the prolactin response to thyrotropin-releasing hormone by low-dose dopamine infusion in women with pathological hyperprolactinemia.

Previous studies in Rhesus monkeys have demonstrated that a dopamine (DA) infusion rate of 0.1 microgram/kg X min induces peripheral DA levels similar to those measured in hypophysial stalk blood and normalizes serum prolactin (PRL) levels in stalk-transected animals. We therefore examined the effect of such DA infusion rate on basal and thyrotropin-releasing hormone (TRH)-stimulated PRL secretion in both normal cycling women and women with pathological hyperprolactinemia. 0.1 microgram/kg X min DA infusion fully normalized PRL serum levels in 8 normal cycling women whose endogenous catecholamine synthesis had been inhibited by alpha-methyl-p-tyrosine (AMPT) pretreatment. Furthermore, DA significantly reduced, but did not abolish, the rise in serum PRL concentrations induced by both acute 500 mg AMPT administration and 200 micrograms intravenous TRH injection in normal women. A significant reduction in serum PRL levels in response to 0.1 microgram/kg X min DA, similar to that observed in normal cycling women when expressed as a percentage of baseline PRL, was documented in 13 amenorrheic patients with TRH-unresponsive pathological hyperprolactinemia. However, a marked rise was observed in the serum PRL of the same patients when TRH was administered during the course of a 0.1-microgram/kg X min DA infusion. The PRL response to TRH was significantly higher during DA than in basal conditions in hyperprolactinemic patients, irrespective of whether this was expressed as an absolute increase (delta PRL 94.4 +/- 14.2 vs. 17.8 +/- 14.1 ng/ml, p less than 0.002) or a percent increase (delta% PRL 155.4 +/- 18.9 vs. 17.9 +/- 7.1, p less than 0.0005), and there was a significant linear correlation between the PRL decrements induced by DA and the subsequent PRL responses to TRH. These data would seem to show that the 0.1-microgram/kg X min DA infusion rate reduces basal PRL secretion and blunts, but does not abolish, the PRL response to both TRH and acute AMPT administration. The strong reduction in PRL secretion and the restoration of the PRL response to TRH by 0.1 microgram/kg X min DA infusion in high majority of hyperprolactinemic patients, seem to indicate that both PRL hypersecretion and abnormal PRL response to TRH in women with pathological hyperprolactinemia are due to a relative DA deficiency at the DA receptor site of the pituitary lactotrophs.

Adult↗
PubMed1984

Testosterone-induced hyperprolactinaemia in a patient with a disturbance of hypothalamo-pituitary regulation.

A case of a patient with hypopituitarism due to a disturbance of hypothalamo-pituitary regulation is presented, who developed high-grade hyperprolactinaemia after the initiation of substitutive therapy with testosterone esthers. The increase in serum Prl was strictly related to testosterone aromatization to oestradiol, since anti-oestrogen compounds were effective in reducing (clomiphene) or abolishing (tamoxifen) the enhanced Prl secretion. The oestrogen effect in raising Prl release was not attributable to a reduction in the dopamine inhibition of Prl-secreting cells, as the dopamine-antagonist domperidone failed to increase Prl serum levels in the same patient. This suggests that, in man, the oestrogen effect in enhancing Prl release is mainly enacted directly on the pituitary lactotrophs rather than exerted through a reduction in the hypothalamic dopamine activity.

Adult↗
PubMed1983

Suppressive effect of long term sulfonylurea treatment on A, B, and D cells of normal rat pancreas.

The effect of chronic administration of tolbutamide (150 mg/kg X day, orally, over 60 days) and glibenclamide (1 mg/kg X day, orally, over 60 days) on pancreatic A, B, and D cell function was investigated in male nondiabetic rats. In a first set of experiments pancreatic hormonal response to metabolic stimuli was evaluated during glucose (11.1 mM) or arginine (10 and 20 mM) infusion in the isolated perfused rat pancreas. The basal levels of insulin (IRI) and glucagon (IRG) were similar in control and in sulfonylurea-treated rats. Tolbutamide treatment markedly depressed the IRI response to glucose (P less than 0.005) or arginine (P less than 0.0005) infusion and the IRG response to arginine (P less than 0.01). After glibenclamide treatment, IRI decreased significantly (P less than 0.0005 and P less than 0.005, respectively) only in response to arginine infusion. This effect was still evident 10 days after the end of treatment. Furthermore, long term glibenclamide administration suppressed somatostatin (SRIF) response to glucose (P less than 0.0005) or arginine (P less than 0.0005). In a different group of rats treated with glibenclamide (1 mg/kg X day, orally, over 60 days) IRI, IRG, and SRIF plasma concentration and blood glucose levels were examined at the end of treatment. The results did not differ significantly from those of a control group. In the same animals, pancreatic IRI, IRG, and SRIF content, measured on acid-ethanol extracts, was reduced (P less than 0.1 vs. controls). These data clearly indicate that long term treatment with sulfonylurea drugs has a suppressive effect on pancreatic endocrine function in rats. The concomitant involvement of A, B, and D cell suggests that this effect is not specific.

Animals↗
PubMed1982

[Hypokalemic myopathy in arterial hypertension].

Three cases of arterial hypertension and severe hypokaliemia are reported; in two cases an acute rhabdomyolisis was also observed. The syndrome was iatrogenic in two cases depending on the licorice eating and the combined use of diuretics and a 9-alpha-fluoroprednisolone-containing nasal spray in one patient, and on a long-term use of the same nasal decongestant in the other. In the patient 2 the persistence of low PRA and aldosterone levels seems to indicate an excess of mineralcorticoid activity other than aldosterone. The syndrome of factitious mineralcorticoid excess should, therefore, be considered in the differential diagnosis of arterial hypertension with hypokaliemia; the risks of a long-term administration of steroid-containing nasal sprays, responsible of serious side effects, should also be stressed.

Adult↗
PubMed1982

DHT-receptor in cultured human fibroblasts: binding study in a family with androgen insensitivity (complete testicular feminisation).

3H-DHT binding was examined in cultured skin fibroblasts from a patient with complete testicular feminisation (CTF), from his heterozygote mother, and his clinically normal sister, who menstruated normally. Binding parameters were: Bmax less than 1 fmol/mg protein and KD unmeasurable in CTF; Bmax = 24 fmol/mg protein and KD = 3.63 X 10(-9) mol/l in the mother; and Bmax = 46 fmol/mg protein and KD = 3.7 X 10(-9) mol/l in the sister. Five cultures obtained from genital and non-genital skin of normal male and female subjects were used as controls, in which Bmax ranged from 37 to 62 fmol/mg and KD from 2.0 to 3.6 X 10(-9) mol/l. The considerable reduction of Bmax in the obligate heterozygote and the normal binding capacity in the sister, a probable heterozygote, suggests that it may be possible to use the DHT-receptor assay to identify carriers in families with androgen resistance.

Adolescent↗
PubMed1982

Characterization of adrenergic control of glucagon secretion from isolated perfused rat pancreas.

In order to characterize the adrenergic control of the pancreatic A cell the effect on glucagon secretion of three sympathomimetic substances - epinephrine, isoproterenol and phenylephrine - and two adrenergic blocking agents - propranolol and phentolamine - were tested separately in the basal state and during glucagon hypersecretion induced by arginine infusion or glucopenia, using the isolated perfused rat pancreas. Epinephrine and isoproterenol infusion caused a prompt and sustained glucagon release in the basal state and potentiated glucagon response to metabolic stimuli. Insulin secretion was suppressed by epinephrine and slightly stimulated by isoproterenol. The stimulatory effect on glucagon secretion observed during phenylephrine infusion was abolished by concomitant propranolol infusion and potentiated by phentolamine. Insulin secretion was markedly depressed by phenylephrine: this effect was reserved by concomitant phentolamine infusion, while no effect was observed by concomitant propranolol infusion. Propranolol caused a suppression of both glucagon and insulin secretion, while phentolamine slightly enhanced glucagon and insulin production. In conclusion, beta-adrenergic receptor stimulation markedly increased pancreatic glucagon secretion and slightly enhanced pancreatic beta-cell activity; conversely, alpha-adrenergic agents markedly depressed insulin secretion while scarcely influencing glucagon production.

Animals↗
PubMed1981

[Adrenergic control of pancreatic glucagon secretion].

In order to characterize the adrenergic control of pancreatic A cell, the effect on the glucagon secretion of three sympathomimetic substances (epinephrine, isoproterenol, phenylephrine) and two adrenergic blockers (propranolol and phentolamine) have been separately examined by the isolated perfused rat pancreas. The study was performed in basal state and during glucagon hypersecretion induced by arginine or glucopenia. Epinephrine and isoproterenol infusion determined a prompt an sustained glucagon release both in the basal state and during glucagon hypersecretion. The effect of phenylephrine infusion was slight. In the presence of propranolol, glucagon secretion induced by metabolic stimulus was significantly depressed. The glucagon secretion in the same experimental conditions was insignificantly enhanced by phentolamine. Finally propranolol infusion reverse the glucagon secretion induced by phenylephrine. In conclusion the pancreatic glucagon secretion in our model of study is clearly induced by B adrenergic receptor stimulation.

Animals↗
PubMed1981

[Typing of the alpha adrenergic receptors of pancreatic B cells. In vitro studies with the isolated and perfused rat pancreas].

Two groups of receptors, one which develops a stimulating effect (alpha 1), the other an inhibitory effect hae recently been isolated in the alpha adrenergic group. In order to type the B cell adrenergic receptor of the endocrine pancreas, which mediates the inhibitory action exerted by the catecholamines on insulin secretion, the release of this hormone was evaluated in the presence of five alpha simpathomimetic substances that have a decreasing degree of efficiency on the adrenergic alpha 2 receptor of the presynaptic sympathic nerve terminal. The order of potency with which the alpha agonists tested depressed IRI secretion is superimposable on that of their potency on the sympathetic nerve and alpha 2 receptor. We concluded that adrenergic inhibition of insulin secretion is mediated by an alpha 2 receptor.

Adrenergic alpha-Agonists↗
PubMed1981

[A new model for the in vitro study of the entero-island of Langerhans axis].

A new in vitro pancreas-intestine model which makes it possible to study the physiopathology of the intero-insular axis in greater depth, as it eliminates interference from other system, is proposed. The model, which is composed of the rat pancreas, duodenum and the first 25 cm of the small intestine, conserves both the circulation and the in vivo anatomical reltionship intact. Experiments were designed to evaluate the effect of a drug-induced disaccharidase-activity block on insulin secretion. The results obtained confirm the validity of the proposed model in investigating the entero-insular axis.

Acarbose↗
PubMed1981

Progesterone positive feedback on gonadotropin release in estrogen-primed postmenopausal women: central nervous system and pituitary as possible sites of action.

To investigate the site and mode of action of progesterone in inducing gonadotropin release, the effects of catecholamine-depleting (methyldopa) or dopamine agonist (bromocriptine) drugs on progesterone positive feedback and the gonadotropin response to a centrally acting noradrenergic drug (clonidine) were evaluated in estrogen-primed postmenopausal women. Progesterone administration induced a significant rise in LH, FSH, and PRL serum levels in the control group. Bromocriptine administration was followed by a marked suppression of PRL release but did not modify the gonadotropin response to progesterone. Methyldopa pretreatment significantly reduced the progesterone-induced LH surge, while PRL release was unaffected. After estrogen priming, clonidine administration did not result in an increase in serum LH or FSH concentrations. The dissociated responses of LH and PRL in bromocriptine-pretreated subjects and the significant reduction of the LH rise after progesterone in methyldopa-pretreated women seem to invalidate the hypothesis that a fall in endogenous dopamine is responsible for progesterone positive feedback and suggest that neural noradrenergic mechanisms are involved in progesterone-induced gonadotropin release. The ineffectiveness of a centrally acting noradrenergic agonist in inducing gonadotropin rise provides indirect evidence that an increased pituitary responsiveness may also be involved in progesterone positive feedback.

Aged↗
PubMed1981

Effect of estrogens and progesterone on gonadotropin and prolactin release in a patient with androgen insensitivity.

Response of serum levels of gonadotropins and prolactin to doses of estrogen and progesterone was measured in a patient with the complete form of androgen insensitivity, ie, testicular feminization. Before gonadectomy a single 2.5-mg dose of estradiol benzoate (E2B) produced a decrease in gonadotropin levels. Gonadectomy resulted in a rise of serum levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) but had no effect on levels of prolactin. The following results were obtained after gonadectomy: During low-dosage therapy with ethinyl estradiol (EE) a single 2.5-mg dose of E2B produced a decrease in FSH and LH levels, no LH surge, and a small rise in prolactin levels. With a tenfold higher EE priming, the same dose of E2B provoked an LH surge; progesterone administration produced FSH, LH, and prolactin release. However, progesterone priming blocked the positive feedback of estradiol and enhanced its negative feedback. Pituitary sensitivity ot nonandrogenic steroids appears to be normal in cases of testicular feminization. Under this condition, after gonadectomy, the dynamics of gonadotropins and prolactin in response to estrogens or progesterone administration are similar to those in normal women and suggest that aromatization products of testosterone do not produce any irreversible effects on neuroendocrine differentiation of androgen-insensitive patients

Adult↗
PubMed1980

[The amenorrhea-galactorrhea syndrome. Clinical and therapeutic aspects of 5 treated cases].

The behaviour of plasma prolactin in response to various pharmacological tests has been examined together with that of other hypophyseal function parameters in five patients suffering from amenorrhoea-galactorrhoea syndrome. Evaluation of plasma prolactin and hypophyseal tropinic reserve levels did not prove sufficient to discriminate between functional and organic forms of hyperprolactinaemia. A woman patient was submitted to neurosurgical operation for removal of a hypophyseal microadenoma. The other patients were treated medically with 2-alpha-bromoergocryptin which produced quick normalization of prolactinaemia with restoration of normal memstrual cycles and cessation of galactorrhoea.

Adenoma↗