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Biomedical subjects

D Cocchi

Publications and source records attributed to D Cocchi.

At least 91 records · Page 5Linked to original sources
PubMed1984

Prolactin control by the tubero-infundibular GABAergic system: role of anterior pituitary GABA receptors.

Anterior pituitary (AP) GABA receptors have been shown to play a functional role in the inhibitory control of prolactin (PRL) secretion by this amino acid. However, the physiological significance and the pharmacological characteristics of these receptors have yet to be determined. In normal male rat AP's incubated in vitro, GABA (10(-6) M) is effective in decreasing PRL release only when incubated in the presence of ethanolamine-O-sulphate (EOS), a potent GABA-transaminase (GABA-T) blocker. The failure of GABA alone to inhibit PRL release in vitro could be explained by the rapid degradation of the amino acid when added to the medium by AP-GABA-T. Central nervous system (CNS)- and AP-GABA receptors present similar affinity constants when evaluated by Scatchard analysis. However, displacement studies show that AP-GABA receptors have 10- and 100-times less affinity for muscimol (M), a GABA agonist, and for bicuculline, a GABA antagonist, respectively, than have GABA receptors. The low affinity of the agonist towards the AP receptors could also account for the relatively poor sensitivity of lactotrophs to GABA-mimetic compounds. Failure of chronic treatment with aminooxyacetic acid, a GABA-T inhibitor, to modify the PRL-lowering effect of GABA-mimetic compounds, despite the decrease in the number of AP-GABA receptors, indicates that in normal conditions only a reduced number of receptors are operative. These studies of AP-GABA receptors provide insight for a better understanding of the mechanisms involved in the regulation of PRL secretion by the hypothalamic GABAergic system.

Animals↗
PubMed1984

Daily fluctuations in the activity of the tuberoinfundibular GABAergic system and plasma prolactin levels.

In view of the role exerted by gamma-aminobutyric acid (GABA) in the control of prolactin (PRL) secretion the circadian periodicity of hypothalamo-pituitary GABAergic activity and PRL secretion was evaluated in adult male rats to ascertain if a meaningful correlation between biochemical and endocrine indices may be evidenced. Anterior pituitary and median eminence GABA concentrations peaked during the late afternoon hours (18.00 h), while the glutamic acid decarboxylase activity reached higher concentrations at 15.00 h. Plasma PRL presented two circadian surges at 15.00 h and at midnight. Although the changes of GABA in the hypothalamo-pituitary complex and the PRL surges did not show a close temporal relation, the possibility may be considered that GABA circadian changes occurred as a delayed response to PRL circadian surges. However, it cannot be excluded that changes in the biochemical indices could be related to other neuroendocrine events.

Animals↗
PubMed1984

In vivo supersensitivity of the anterior pituitary of old female rats to dopaminergic inhibition of prolactin secretion.

Old female rats (20-27 months) were given acute administration of an indirectly acting dopamine (DA) agonist, nomifensine or scalar doses of the direct DA receptor agonist, bromocriptine. Young female rats (4-9 months) were used as controls. Nomifensine (10 mg/kg i.p.) decreased significantly basal prolactin (PRL) levels in young rats as in old rats. In young rats, bromocriptine decreased significantly basal PRL levels only at the dose of 0.5 mg/kg intraperitoneally, the doses of 0.1 and 0.02 mg/kg being ineffective. In contrast, in old rats administration of 0.02 mg/kg of bromocriptine consistently inhibited basal PRL levels and the maximum PRL-lowering effect was already evident at the dose of 0.1 mg/kg. These data indicate that the pituitary of old rats, due to the age-related removal of dopaminergic inputs from the tuberoinfundibular system, becomes supersensitive to direct dopaminergic stimulation. This phenomenon may explain the normal PRL responsiveness of old rats to nomifensine, despite defective tuberoinfundibular dopaminergic function.

Adenoma↗
PubMed1984

Gonadal steroid modulation of naloxone-induced LH secretion in the rat.

The effect of acute administration of the opioid receptor antagonist naloxone hydrochloride (5 mg/kg, s.c.) on plasma LH levels was evaluated in female and male rats 24, 36 and 48 h and 1, 3 and 5 weeks after gonadectomy and in 5-week gonadectomized rats after acute or chronic (2 weeks) administration of oestradiol benzoate (OB, 10 micrograms/rat per day, s.c.), testosterone propionate (TP, 150 micrograms/rat, s.c.) or dihydrotestosterone propionate (DHT, 150 micrograms/rat, s.c.) respectively. Concurrent evaluation of plasma LH after administration of LH releasing hormone (LHRH, 1 microgram/kg, i.p.) was performed in the same experimental groups. In rats of both sexes, a significant rise in plasma LH after naloxone was observed in sham-operated and recently gonadectomized rats (24-48 h); in female rats 36 and 48 h after gonadectomy the rise was higher than in controls. One, 3 and 5 weeks after gonadectomy, naloxone failed to stimulate LH release in both female and male rats. In gonadectomized rats undergoing steroid replacement therapy, OB administered 72 h before testing, TP (16 and 72 h) and DHT (16 h) were the most effective in reinstituting the LH response to naloxone. Chronic administration of gonadal steroids did not restore normal LH responsiveness to naloxone. In most experimental groups, LH responses after naloxone were clearly unrelated to pituitary LH responsiveness to LHRH, which indicates that the opioid antagonist was acting via the central nervous system.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Neuroendocrine studies with fluvoxamine: animal data.

1 Administration of the potent 5-hydroxytryptamine (5-HT) re-uptake inhibitor fluvoxamine (25 mg/kg i.p. for 14 days) to adult cycling female rats did not alter either the number of oestrous episodes or the plasma concentrations of luteinizing hormone determined on days 2, 9 and 14 of treatment. 2 Fluvoxamine (25 mg/kg i.p.) induced in male rats a clear-cut lowering of beta-endorphin-like immunoreactivity from the anterior pituitary, but not the neurointermediate lobe, and increased concomitantly plasma levels of beta-endorphin and beta-lipotropin. 3 Fluvoxamine (12.5 and 25 mg/kg i.p.) stimulated, although not strikingly, prolactin (PRL) secretion in adult male rats, and at 25 mg/kg i.p. potentiated the PRL-releasing effect of 5-hydroxytryptophan (30 mg/kg i.p.). 4 In male rats treated daily with fluvoxamine (25 mg/kg i.p.) the PRL-releasing effect of an additional acute fluvoxamine administration (same dose) was abolished after 4 days maintenance treatment. One week after withdrawal of maintenance, which had been given for 14 days, the challenge dose of fluvoxamine was still unable to raise plasma PRL levels. 5 The endocrine effects of acute fluvoxamine administration are compatible with activation of 5-HT neurotransmission in the central nervous system. The mechanism(s) underlying tolerance to the PRL-releasing action of the drug is presently obscure. Its elucidation should provide insight into the mechanism of action of antidepressant drugs affecting 5-HT function.

5-Hydroxytryptophan↗
PubMed1983

Ethanolamine-O-sulfate enhances gamma-aminobutyric acid secretion into hypophysial portal blood and lowers serum prolactin concentrations.

In ovariectomized rats the intraventricular administration of ethanolamine-O-sulfate (EOS, 300 micrograms), a specific, competitive and catalytic inhibitor of gamma-aminobutyric acid (GABA) transaminase, induced 3-4 h later a marked reduction in serum prolactin (PRL) concentrations and a 3- to 4-fold rise in the concentration of GABA in pituitary stalk, but not systemic, plasma. The administration of EOS also resulted in an elevation of GABA concentrations in the hypothalamus. These results demonstrate that GABA in pituitary stalk plasma is derived from the central nervous system and that an abrupt increase in the concentration of GABA in hypophysial portal blood is associated with a suppression of PRL secretion.

Animals↗
PubMed1983

Tubero-infundibular dopaminergic function in cirrhotic patients: evaluation by nomifensine and domperidone.

Cirrhotic patients reportedly show alterations of anterior pituitary hormone secretion, which may reflect an underlying defective central neurotransmitter function. In this study, we have investigated the catecholaminergic control of prolactin (Prl) and growth hormone (GH) secretion in cirrhotic patients by means of an indirectly acting dopamine (DA) and norepinephrine agonist, nomifensine (Nom), and a DA receptor antagonist, domperidone (Dom). Basal GH levels were higher in the 12 female and male cirrhotic patients than in the 12 age- and sex-matched normal controls, while no difference was present in basal Prl values. Administration of Nom (200 mg po) suppressed basal Prl levels (at least 30% inhibition at three consecutive times post-drug administration) in 6/12 controls and in 6/12 cirrhotic patients, the frequency of negative responses not being different between the two groups. Nom induced a slight elevation of GH levels in controls, and evoked a more marked and sustained GH increase in cirrhotic patients. Administration of Dom (4 mg iv) induced similar Prl increments in 6 male controls and 6 male cirrhotic patients. Normal Prl responsiveness to Nom and Dom points to the existence of preserved tubero-infundibular DA function and modulation of pituitary DA receptors in the cirrhotic patients investigated. Higher GH responsiveness to Nom is compatible with a different bioavailability of the drug.

Adult↗
PubMed1983

Prolactin-lowering and -releasing drugs. Mechanisms of action and therapeutic applications.

Drugs whose systemic and/or central administration induce suppression or stimulation of prolactin secretion are reviewed. The most commonly used prolactin-lowering drugs include: (a) direct-acting dopamine receptor agonists (e.g. dopamine, apomorphine and the ergot derivatives); (b) indirect-acting dopamine agonists (e.g. amphetamine, nomifensine, methylphenidate, amineptine); (c) drugs which impair serotoninergic neurotransmission (e.g. the neurotoxin 5,7-dihydroxytryptamine and the serotonin receptor antagonists methysergide and metergoline); (d) gamma-aminobutyric acid [GABA]-mimetic drugs (e.g. GABA, muscimol, ethanolamine-O-sulphate, sodium valproate); (e) histamine H2-receptor agonists; and (f) cholinergic (muscarinic and nicotinic) receptor agonists. Major prolactin-stimulating agents comprise: (a) dopamine receptor antagonists (e.g. classic and atypical antipsychotic drugs); (b) drugs differently capable of impairing central nervous system dopamine function (e.g. blockers of dopamine neurotransmission such as alpha-methyl-p-tyrosine and 3-iodo-L-tyrosine, false precursors such as alpha-methyldopa, and inhibitors of L-aromatic amino acid decarboxylase such as carbidopa and benserazide); (c) drugs enhancing serotoninergic neurotransmission (e.g. the serotoninergic precursors tryptophan and 5-hydroxytryptophan, direct-acting serotonin agonists such as quipazine and MK 212, and indirect-acting serotonin agonists such as fenfluramine); (d) blockers of serotonin reuptake (e.g. fluoxetine, fluvoxamine and clovoxamine); (e) H1-receptor agonists; and (f) H2-receptor antagonists (e.g. cimetidine). Some of the above classes of drugs (e.g. the indirect-acting dopamine agonists, dopamine receptor antagonists, GABA-mimetic drugs, dopamine receptor blocking drugs, and H2-antagonists) may be useful for selecting among hyperprolactinaemic patients those with a prolactin-secreting tumour in an early stage of the disease. Direct-acting dopamine receptor agonists, notably the ergot derivatives; are potent antigalactopoietic agents, can revert impaired gonadal function to normal in both female and male patients with hyperprolactinaemia, and may have antiproliferative effects on pituitary prolactin-secreting tumours. All prolactin-stimulating agents, but especially the dopamine receptor antagonists, are liable to induce alterations in gonadal function in subjects of either sex. In addition to their usage for diagnostic or therapeutic purposes, the above drugs appear to be invaluable tools for enabling a better understanding of the neurotransmitter control of prolactin secretion.

Animals↗
PubMed1982

GABAergic control of anterior pituitary hormone secretion.

Anatomical and biochemical studies have identified a hypothalamic tubero-infundibular GABAergic system, which plays a functional role on anterior pituitary hormone secretion. Experimental and clinical evidence support the presence of a dual component in the action of GABA; one mediated via the central nervous system and the other exerted directly at the anterior pituitary level. The two sites of action may be responsible for the excitatory and inhibitory effects of GABA on pituitary hormone and especially prolactin secretion. The future characterization of this system will provide a better understanding of the involvement of GABA in the physiology of anterior pituitary hormone secretion and will contribute to the development of new pharmacological agents for the therapy of neuroendocrine disorders.

Adrenocorticotropic Hormone↗
PubMed1982

ACTH1-24 counteracts the prolactin-releasing effect of an opioid.

The administration of the synthetic and stable opioid peptide[D-Ala2,MePhe4,Met(O)5o1]enkephalin (FK 33-824) at the dose of 0.2 mg/kg i.v. induced a rise in plasma levels of prolactin in the rat, an effect which was prevented by 1 mg/kg i.v. of the opiate antagonist naloxone. A simultaneous i.v. injection of 20 microgram/kg i.v. of ACTH1-24 significantly reduced the prolactin releasing effect of FK 33-824, therefore giving further evidence of an in vivo interaction between ACTH-related peptides and opioid peptides.

Adrenocorticotropic Hormone↗
PubMed1982

Growth hormone response to thyrotropin-releasing hormone in liver cirrhosis: unique alteration in anterior pituitary responsiveness to hypothalamic hormones.

Patients with chronic liver diseases were evaluated for: 1) the ability of somatostatin to affect the thyrotropin-releasing hormone (TRH) induced growth hormone (GH) rise; 2) the competence of luteinizing-hormone releasing hormone (LH-RH) to release GH; 3) the non-specific releasing effect of TRH and LH-RH on other anterior pituitary (AP) hormones. In 6 patients, infusion of somatostatin (100 micrograms iv bolus + 375 micrograms i.v. infusion) completely abolished the TRH (400 micrograms i.v.)-induced GH rise; in none of 12 patients, of whom 7 were GH-responders to TRH, did LH-RH (100 micrograms i.v.) cause release of GH; 4) finally, LH-RH (12 patients) did not increase plasma prolactin (PRL) and TRH (7 patients) did not evoke a non-specific release of gonadotropins. It is concluded that: 1) abnormal GH-responsiveness to TRH is the unique alteration in AP responsiveness to hypothalamic hormones present in liver cirrhosis; 2) the mechanism(s) subserving the altered GH response to TRH is different from that underlying the TRH-induced GH rise present in another pathologic state i.e. acromegaly, a condition in which the effect of TRH escapes somatostatin suppression and LH-RH evokes GH and PRL release.

Adult↗
PubMed1982

Thyrotrophin and prolactin responses to thyrotrophin-releasing hormone in patients with Parkinson's disease.

The thyrotrophin (TSH) and prolactin (Prl)-releasing effects of TSH-releasing hormone (TRH) were investigated in 20 subjects with Parkinson's disease (PD), unmedicated, on chronic treatment with a combination levodopa-benserazide (Madopar) or levodopa-carbidopa (Sinemet) or withdrawn from therapy. Administration of TRH (200 micrograms iv) induced in unmedicated patients TSH and Prl responses significantly lower than those of sex-and age-matched controls. In patients on Madopar therapy the TSH and Prl responses to TRH were greater than in unmedicated patients and comparable to those of controls, while in patients on Sinemet therapy the pituitary responses were undistinguishable from those of unmedicated subjects. Withdrawal of Madopar therapy resulted in a marked diminution of the TSH response but did not affect the Prl response to TRH. Withdrawal of Sinemet therapy did not alter the TSH and Prl responses to TRH. Concomitant evaluation of growth hormone (GH) levels, in none of the subjects evidenced non-specific changes in plasma GH following TRH. Since TSH and Prl responses to TRH are inhibited by an enhancement of the dopaminergic tone, it would appear that the latter is preserved in the tuberoinfundibular system of unmedicated subjects and subjects on chronic Sinemet therapy, but is defective in subjects on chronic Madopar therapy.

Adult↗