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Biomedical subjects

G Trasforini

Publications and source records attributed to G Trasforini.

At least 55 records · Page 3Linked to original sources

Cholinergic mediation in dermorphin-induced growth hormone secretion in man.

The effects of pirenzepine (P), a cholinergic muscarinic antagonist, on growth hormone (GH) and prolactin (PRL) response to dermorphin (D) were studied in a group of 7 healthy men. D produced clear elevations in GH and PRL levels. P completely blocked the GH-releasing activity of D, whereas it did not alter the PRL-releasing activity. These results indicate that GH-releasing action of D is mediated via the central cholinergic nervous system in man.

Adult↗

Prolactin releasing and luteinizing hormone inhibiting activity of dermorphin shorter homologues in the rat.

Dermorphin, a heptapeptide isolated from the skin of the frogs Phillomedusa sauvagei and Phillomedusa rhodei, is endowed with potent peripheral and central opioid-like activity. Intracerebroventricular (icv) injection of dermorphin (31.2, 62.5 and 125 pmol/100g) induced in ovariectomized (OVX) rats dose related rises and decreases in prolactin (PRL) and luteinizing hormone (LH) levels, respectively. The aim of this work was to evaluate the same endocrine responses after administration of shorter peptide amide homologues, related to the N-terminal sequence of dermorphin. These compounds retain a substantial analgesic activity although the latter decreases with the decrease in the number of amino acid residues. Icv administration of the hexapeptide homologue (dermorphin 1-6 amide) to OVX rats did not induce any PRL rise or LH inhibition, even at the high dose of 250 pmol/100g. The pentapeptide (dermorphin 1-5 amide), instead, increased PRL and decreased LH secretion, although the effect was significant only at the dose of 250 pmol/100g. Administration of the tetrapeptide (dermorphin 1-4 amide) induced a significant PRL rise and LH inhibition at both the doses of 125 and 250 pmol/100g. The tetrapeptide was the smallest fragment of the dermorphin moiety which caused endocrine responses while the tripeptide (dermorphin 1-3 amide) was completely ineffective in this context. These data indicate that a complete dissociation exists between the behavioral and endocrine effects of the dermorphin homologues examined. In fact, shorter dermorphins whose analgesic potency was directly related to the number of amino acids, exhibited an opposite pattern in evoking endocrine effects.

Analgesics↗

Prolactin and growth hormone responses to dermorphin in patients with prolactin-secreting pituitary adenoma.

We have recently shown that dermorphin (D), a new potent opioid peptide (H-Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2) stimulates prolactin (PRL) and growth hormone (GH) secretion in humans. In 11 patients with a PRL-secreting pituitary adenoma (eight microprolactinomas and three macroprolactinomas with suprasellar extension), diagnosed by pituitary dynamic function tests, and radiological evidence with confirmation at surgery, the PRL and GH responses to D were studied to evaluate the effect of pathological hyperprolactinemia on the opioid-induced secretion of GH and PRL. No PRL response to D was observed in all 11 patients. Plasma GH increased after D in all patients, except in three patients bearing a macroprolactinoma. This study shows that the effect of D on PRL and GH secretion can be dissociated in patients with PRL-secreting pituitary adenoma, perhaps for a different derangement in the hypothalamic-pituitary mechanism(s) underlying the opioidergic regulation of GH and PRL secretion. In addition our data indicate that D can be employed as a useful opioid probe in humans.

Adenoma↗

The effects of dermorphin on the endocrine system in man.

This paper summarizes the results of our recent studies in a group of healthy subjects on the endocrine effects of the new potent opioid peptide, dermorphin (H-Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2), originally isolated from amphibian skin. Intravenous infusion (5.5 microgram/kg/min for 30 min) of dermorphin (D) significantly increased plasma levels of prolactin (PRL), growth hormone (GH), thyrotropin (TSH) and renin activity (PRA), but decreased plasma levels of cortisol. D produced a small decrease in ACTH, and a small increase in plasma aldosterone. Pretreatment with the opioid receptor antagonist naloxone (N) suppressed the PRL and TSH response to D, blunted the D-induced GH and PRA increase, and completely prevented the D-induced plasma cortisol decrease, but enhanced plasma cortisol and ACTH levels. These data indicate that the action of D is mediated through opioid receptors, and are consistent with the conclusion that: (1) D, a new opioid peptide, can stimulate PRL, GH and TSH release in humans; (2) D increases PRA levels, perhaps via activation of the sympathetic nervous system, providing evidence that opioid peptides may exert an influence on renin secretion; (3) D suppresses plasma cortisol levels, by affecting ACTH secretion, corroborating previous observations that opioid peptides might affect the function of the pituitary-adrenocortical axis.

Adrenocorticotropic Hormone↗

Dermorphin reduces the metyrapone-evoked release of adrenocorticotropin, beta-endorphin, and beta-lipotropin in man.

The aim of this study was to investigate further the influence of dermorphin (D), a new potent opioid peptide (H-Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2), on the functional activity of the pituitary-adrenocortical system in man. Six normal men were treated with oral metyrapone to stimulate the secretion of ACTH, beta-lipotropin, and beta-endorphin. In these subjects, significant suppression of metyrapone-evoked release of ACTH and related peptides occurred during D infusion (5.5 micrograms/kg X min for 30 min) compared with that during saline infusion. These results indicate that D can induce a significant decline in plasma levels of ACTH, beta-lipotropin, and beta-endorphin, the major circulating peptides from the C-terminal part of proopiocortin, and suggest that opioid peptides may be involved in the control of the functional activity of pituitary-adrenocortical activity in man.

Adrenocorticotropic Hormone↗

Effect of somatostatin on growth hormone and prolactin response to dermorphin in man.

The effects of iv somatostatin (somatotrophin release inhibiting factor (SRIF) on growth hormone (GH) and prolactin (Prl) response to dermorphin (D) were tested in 6 healthy men. In all subjects D induced a significant increase in GH and Prl levels, as expected. SRIF completely blocked the GH-releasing activity of D, whereas it only reduced the Prl-releasing activity. The results confirm that D is a potent stimulant for GH and Prl release in man, and furthermore demonstrate that the action of D on GH secretion can be completely overridden by SRIF.

Adult↗

Dermorphin, a new opioid peptide, stimulates thyrotropin secretion in normal subjects.

The effect of a recently described, potent opioid peptide, dermorphin (DER), on TSH secretion in euthyroid subjects has been studied. DER infused at a rate of 5.5 micrograms/Kg/min for 30 min induced a significant increase in serum TSH concentration at 60, 90, and 120 min after the infusion was begun. Treatment with naloxone administered 30 min before the DER infusion with a bolus dose of 4 mg, followed by a constant infusion of 1 microgram/Kg/min for 150 min, prevented the rise in serum TSH. Naloxone administered alone did not induce any change in TSH concentration. The present findings suggest that DER has a stimulatory effect on TSH secretion, probably mediated by opioid receptors. These results, however, do not solve the question as to whether opioids have a physiological role in the control of pituitary TSH secretion.

Adolescent↗

Stimulatory effect of dermorphin, a new synthetic potent opiate-like peptide, on human growth hormone secretion.

Two new related heptapeptides (dermorphins) with potent central and peripheral opiate-like activity have been isolated from the skin of South American frogs, and have been chemically characterized as H-Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2 (dermorphin) and H-Tyr-D-Ala-Phe-Gly-Tyr-Hyp-Ser-NH2 (Hyp6-dermorphin). The response of GH to infusion of a synthetic dermorphin (5.5 micrograms/kg/min for 30 min) was studied in 9 healthy men. Dermorphin (D) significantly increased plasma growth hormone (GH) concentrations. The GH response to D was blunted by prior administration of naloxone, suggesting that D interacts with mu-type opiate receptors. However, the evaluation of the physiological significance of D-induced GH release in humans requires further study.

Adult↗

Effect of pentagastrin on adrenocorticotropin hormone and thyroid-stimulating hormone release in normal subjects.

The possible role of gastrin on TSH, ACTH and cortisol secretion was evaluated by intravenous administration of pentagastrin, the carboxyl-terminal tetrapeptide of gastrin (0.5 microgram/kg b.w.) into 12 healthy subjects. Pentagastrin produced a significant rise in plasma ACTH and cortisol levels but did not alter TSH basal release. These preliminary results suggest that gastrin can influence basal activity of ACTH-cortisol axis. However, further investigation is required to determine its physiological role and mechanisms of action.

Adrenocorticotropic Hormone↗

Effect of ketanserin, an inhibitor of 5-HT2 receptors, on the aldosterone-stimulating action of metoclopramide.

To estimate the possible involvement of a peripheral serotonergic pathway in the mechanism of the aldosterone-stimulating effect of metoclopramide (M) the plasma aldosterone (PA), renin activity (PRA) and prolactin (PRL) response to M was studied in 6 normal subjects before and after administration of ketanserin (K), a pure, specific, and selective blocking agent of 5-hydroxytryptamine type 2 (5-HT2) receptors. With K preadministration the M-induced increase of PRL was similar to that observed in control conditions, in accordance with the specific and peripheral antiserotonergic action of the drug. K potentiated the PA and PRA elevation in response to M. These data suggest that the PA response to M is not related to M's agonist activity at the peripheral 5-HT2 receptors level. The results further indicate that K can induce an enhancement of the activity of renin-angiotensin-aldosterone system with an higher PRA and PA response to stimulatory action of M.

Adolescent↗

Prolactin-releasing activity of dermorphin, a new synthetic potent opiate-like peptide, in normal human subjects.

Dermorphins (D) are heptapeptides (H-Tyr-D-Ala-Phe-Gly-Tyr-X-Ser-NH2; X, Pro or Hyp) with powerful central and peripheral opiate-like activity, originally isolated from the skin of South American frogs. To study the effect of a synthetic D on PRL secretion in man, either D (5.5 micrograms/kg . min for 30 min) or D-placebo (0.9% saline) infusion over 30 min was administered iv in random sequence to 11 volunteers (6 women and 5 men). In all the subjects, D induced a significant increase in the levels of PRL, more consistently in women than in men. To investigate whether the increase in PRL was due to the opiate agonist properties of D, the study was repeated in the same subjects during naloxone infusion. The PRL response to D was completely suppressed, suggesting that the peptide exerts its effect on PRL release via an opiate receptor stimulation of the mu-type. These data allow us to conclude that D may affect PRL release in humans; however, further investigation is necessary before any physiological significance might be attributed to D in man.

Adolescent↗

Responses of plasma renin activity, aldosterone, adrenocorticotropin, and cortisol to dermorphin, a new synthetic potent opiate-like peptide, in man.

This study was designed to investigate the effect of dermorphin (D), a new synthetic potent opiate-like peptide (H-Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2), on PRA, plasma aldosterone (PA), plasma cortisol (PC), and plasma ACTH levels in normal men. D infusion (5.5 micrograms/kg X min for 30 min) significantly increased PRA (P less than 0.01) and decreased PC levels (P less than 0.02). D produced a small decrease in ACTH and a small increase in PA. Pretreatment with the opioid receptor antagonist naloxone (N) blunted the D-induced PRA increase and completely prevented the D-induced PC decrease, but enhanced PC and ACTH levels. These data indicate that the action of D is mediated through opioid receptors, and are consistent with the conclusion that 1) D, a new opioid peptide, increases PRA levels, perhaps via activation of the sympathetic nervous system, providing evidence that opioid peptides may exert an influence on renin secretion; and 2) D suppresses PC levels, perhaps by affecting ACTH secretion, corroborating previous observations that opioid peptides might affect the function of the pituitary-adrenocortical axis.

Adolescent↗

Failure of metergoline to affect the circadian periodicity of plasma cortisol levels in healthy man.

To investigate the role of serotoninergic system on the control of circadian periodicity of human hypothalamic-pituitary-adrenal axis, effect of a potent 5-HT antagonist, metergoline, on diurnal variation in plasma cortisol levels was studied in five male volunteers. The administration of metergoline did not result in a significant change of plasma cortisol concentrations and its circadian rhythmicity. These results suggest that metergoline does not influence the diurnal secretion of cortisol in normal subjects.

Adult↗

Circadian variations of plasma TSH in patients with severe hypothyroidism.

Five patients with severe hypothyroidism were studied to determine diurnal variations in serum TSH and thyroid hormones. The results were based on blood samples withdrawn at 1-h intervals during a 24-h period. A statistically significant circadian rhythm in TSH was detected with the acrophase at 23(30); no significant diurnal periodicity was observed for serum T3. The TSH pattern was similar to that observed in normal and midly hypothyroid subjects, with low levels during the day and higher levels at night. The findings are consistent with the following concepts: a. the TSH circadian rhythm is retained in patients with severe hypothyroidism; b. the abnormality in thyroid function does not effect the regulation of the TSH periodicity.

Adolescent↗

Dermorphin decreases plasma LH levels in human: evidence for a modulatory role of gonadal steroids.

The purpose of this study was to evaluate the effects of dermorphin, a new synthetic powerful opiate-like heptapeptide, on plasma luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in fertile and postmenopausal women. In fertile subjects, dermorphin (5.5 micrograms/kg min for 30 min) decreases plasma LH (p less than 0.01 vs. baseline and placebo values), but not plasma FSH. The area under the curve during dermorphin infusion was significantly lower than during placebo infusion (p less than 0.01). Pretreatment with the opioid receptor antagonist naloxone, blocked the decrease of plasma LH levels. In postmenopausal women not subjected to any treatment, dermorphin infusion did not significantly modify plasma LH and FSH levels. On the contrary, its administration to postmenopausal subjects treated with conjugated estrogens and medroxyprogesterone acetate significantly decreased plasma LH levels (p less than 0.01, vs. baseline, placebo and area under the curve). Considering the modulatory role exerted by ovarian steroids on the activity of such receptors, these data also indicate that opioid systems play a very important part in the hypothalamus-pituitary-ovarian axis.

Adult↗

Effect of ketanserin, a new inhibitor of 5-HT2 receptors, on plasma renin activity and aldosterone levels in normal subject.

The effect of intravenous administration (10 mg) of ketanserin, a pure, specific and selective blocking agent of 5-HT2 receptors (R 41 468: 3-[2-[4-(4-fluorobenzoyl)-1-piperidinyl]ethyl]-2,4(1H,3H)-quinazolinedione) on the renin-angiotensin-aldosterone system and blood pressure in 5 normal male volunteers was compared to the effect of saline alone. Ketanserin induced a small increase in plasma levels of both renin activity and aldosterone, which was not significantly different from that observed during control test. There was no significant effect on systolic and diastolic blood pressure. These preliminary data suggest that 5-HT2 receptors are probably not involved in the physiological control of basal renin secretion. However, further investigations are needed to elucidate the effects of ketanserin on the renin secretion and blood pressure.

Adult↗

[The empty sella syndrome. Clinical, radiological and endocrinologic analysis in 20 cases].

Empty sella syndrome is an anatomical entity in which the pituitary fossa is enlarged and partially filled with cerebrospinal fluid owing to the arachnoid herniation, while the pituitary gland is compressed against the posterior rim of the fossa. This condition can be due to an inherent weakness of the diaphragm sella and/or to an increase in intracranial pressure which promote the herniation of the arachnoid membrane into the pituitary fossa (primary empty sella) or it can results following surgery, radiation or vascular and tumorous pituitary diseases (secondary empty sella). Empty sella can be associated with neuroradiological and endocrine symptoms. This study reports the clinical, endocrine, and roentgenographic features in 20 patients with primary empty sella syndrome. Disturbances of hypothalamic-pituitary function were detected in 6 patients (hyperprolactinemia, hypopituitarism, central diabetes insipidus, hypothalamic hypothyroidism). Three patients exhibited hypergonadotropic hypogonadism. This report supports the following conclusions: a) there is no correlation between size of pituitary fossa, type an extension of arachnoid herniation and the degree of hypothalamic-pituitary dysfunction; b) endocrine alterations are frequent in the empty sella syndrome; c) the association of empty sella and primary diabetes insipidus is not a very rare event.

Adolescent↗