Increased thyrotrophin and prolactin secretion induced by domperidone in hypothyroid subjects

1981 ◽  
Vol 97 (1) ◽  
pp. 48-53 ◽  
Author(s):  
F. Massara ◽  
F. Camanni ◽  
A. Amoroso ◽  
G. M. Molinatti ◽  
E. E. Müller
Keyword(s):  
Anterior Pituitary ◽  
Prolactin Secretion ◽  
Primary Hypothyroidism ◽  
Post Injection ◽  
Clear Cut ◽  
Tsh Secretion ◽  
The Central Nervous System ◽  
Releasing Effect ◽  
Peripheral Site ◽  
Plasma Prl

Abstract. The thyrotrophin (TSH) and prolactin (Prl) releasing effects of domperidone, a recently developed antidopaminergic drug which does not cross the blood-brain barrier, were investigated in 8 women affected by primary hypothyroidism, and were compared to those elicited by another antidopaminergic drug, sulpiride. Domperidone (4 mg iv) induced a clear-cut and sustained rise in both plasma TSH and Prl, with peak levels occurring 15 and 30 min post-injection, respectively. The increments in plasma Prl after domperidone were significantly higher than those in plasma TSH. The TSH and Prl responses induced by domperidone were almost superimposable to those provoked in the same subjects by sulpiride (100 mg im). In view of the inability of domperidone to penetrate into the central nervous system (CNS), these findings imply a 'peripheral' site(s) of action (i.e., anterior pituitary and/or median eminence) for the effect of antidopaminergic drugs on TSH secretion, and, re-iterate the notion that the same 'peripheral' sites are involved in the Prl-releasing effect of these compounds.

THYROTROPHIN RELEASING HORMONE-INDUCED GROWTH HORMONE AND PROLACTIN RELEASE: PHYSIOLOGICAL STUDIES IN INTACT RATS AND IN HYPOPHYSECTOMIZED RATS BEARING AN ECTOPIC PITUITARY GLAND

1977 ◽  
Vol 72 (3) ◽  
pp. 301-311 ◽  
Author(s):  
A. E. PANERAI ◽  
IRIT GIL-AD ◽  
DANIELA COCCHI ◽  
V. LOCATELLI ◽  
G. L. ROSSI ◽  
...  
Keyword(s):  
Pituitary Gland ◽  
Anterior Pituitary ◽  
Time Lapse ◽  
Anterior Pituitary Gland ◽  
Plasma Prolactin ◽  
Thyrotrophin Releasing Hormone ◽  
Releasing Hormone ◽  
Clear Cut ◽  
Urethane Anaesthesia ◽  
Releasing Effect

SUMMARY To determine how the sensitivity of the ectopic anterior pituitary gland to the GH-releasing effect of thyrotrophin releasing hormone (TRH) might be affected by the time lapse from transplantation, TRH (0·15 and 0·6 μg) was injected i.v. into hypophysectomized (hypox)-transplanted rats under urethane anaesthesia 1,3, 8,15, 30 and 60 days after transplantation, and plasma samples were taken 5 and 10 min later. Baseline GH values gradually decreased with time from about 16·0 ng/ml (1 day) to about 3·0 ng/ml (30 and 60 days). The TRH-induced GH release was absent 1 day after transplantation, present only with the higher TRH dose 3 and 8 days after transplantation, and clearly elicitable, also with the lower TRH dose (0·15 μg), from 15 up to 60 days. Determination of plasma prolactin concentrations showed a decline from about 85·0 ng/ml (1 day) to about 32·0 ng/ml (8 days); subsequently (15–60 days) prolactin values stabilized. Plasma prolactin levels increased 15 and 60 days after transplantation only when a dose of 0·6 μg TRH was given. In intact weight-matched rats, TRH induced a GH response only at the dose of 1·2 μg while a short-lived but clear-cut prolactin response could be obtained even with the 0·3 μg dose. The present results indicate that: (1) disconnexion between the central nervous system and the anterior pituitary gland greatly enhances GH responsiveness while blunting prolactin responsiveness to TRH; (2) the sensitivity of the anterior pituitary gland to the GH-releasing effect of TRH increases with time from transplantation; (3) TRH is a more effective prolactin-than GH-releaser on the pituitary gland in situ.

A new pharmacological approach to the diagnosis of hyperprolactinaemic states: the nomifensine test

1980 ◽  
Vol 93 (2) ◽  
pp. 139-148 ◽  
Author(s):  
Andrea R. Genazzani ◽  
Franco Camanni ◽  
Ferdinando Massara ◽  
Enrico Picciolini ◽  
Daniela Cocchi ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Pituitary Adenoma ◽  
Antidepressant Drug ◽  
Sella Turcica ◽  
Pituitary Tumour ◽  
Base Line ◽  
Clear Cut ◽  
The Central Nervous System ◽  
Plasma Prl

Abstract. The prolactin-(Prl) lowering effect of nomifensine (Nom), an antidepressant drug which activates dopamine (DA) neurotransmission mainly by inhibiting DA re-uptake in the central nervous system (CNS), was investigated in normoprolactinaemic subjects, in subjects with physiological puerperal hyperprolactinaemia or pathological hyperprolactinaemia. Nom (200 mg po) administered to 23 normoprolactinaemic women induced a significant decrease in baseline Prl, which was more marked (about 50% inhibition at 120 min) and prompt (30 min) in the subjects who had 'high' Prl levels (>12<20 ng/ml) (13 subjects) than in those with 'low' Prl levels (≤ 12 ng/ml). Also in 9 puerperal women (postpartum day 2) oral administration of 200 mg Nom was followed by a clear-cut decrease of base-line Prl, which started at 30 min and reached nadir values at 150–180 min (about 60% inhibition). Administration of Nom (200 mg po) to 47 subjects with pathological hyperprolactinaemia evidenced the presence of Nom non-responder (36 cases) or responder (11 cases) subjects. In 22 of the Nom non-responder subjects the existence of a Prl-se creting pituitary tumour was established at surgery by selective removal of an adenoma via the transsphenoidal route; of the 14 subjects who did not undergo surgery, 1 had evident and 5 had minor alterations of the sella turcica and, in addition, in 3 subjects the duration of amenorrhoea was longer than 5 years. Only 5 subjects of this group had no radiological alterations of the sella turcica, in presence of basal Prl levels ranging between 50–126 ng/ml. In contrast, 10 out of the 11 Nom-responder subjects had a radiologically normal sella turcica and basal Prl levels lower than 50 ng/ml. Administration of 2-Br-α-ergocriptine (2.5 mg po), a direct stimulant of pituitary DA receptors, to subjects with pathological hyperprolactinaemia (39 cases) induced a striking fall in plasma Prl levels (about 80% inhibition at 240 min), irrespective of the type of Prl responsiveness to Nom. These results indicate that Nom lowers plasma Prl levels in both normoprolactinaemic and hyperprolactinaemic subjects; in the latter, by virtue of its ability to affect selectively DA neurotransmission in the CNS, the drug appears capable of discriminating between individuals with and without pituitary adenoma.

Prolactin: Structure, Function, and Regulation of Secretion

2000 ◽  
Vol 80 (4) ◽  
pp. 1523-1631 ◽  
Author(s):  
Marc E. Freeman ◽  
Béla Kanyicska ◽  
Anna Lerant ◽  
György Nagy
Keyword(s):  
Central Nervous System ◽  
Pituitary Gland ◽  
Anterior Pituitary ◽  
Prolactin Secretion ◽  
Chemical Modifications ◽  
Comprehensive Survey ◽  
The Central Nervous System ◽  
Regulation Of Secretion ◽  
The Brain ◽  
Biological Actions

Prolactin is a protein hormone of the anterior pituitary gland that was originally named for its ability to promote lactation in response to the suckling stimulus of hungry young mammals. We now know that prolactin is not as simple as originally described. Indeed, chemically, prolactin appears in a multiplicity of posttranslational forms ranging from size variants to chemical modifications such as phosphorylation or glycosylation. It is not only synthesized in the pituitary gland, as originally described, but also within the central nervous system, the immune system, the uterus and its associated tissues of conception, and even the mammary gland itself. Moreover, its biological actions are not limited solely to reproduction because it has been shown to control a variety of behaviors and even play a role in homeostasis. Prolactin-releasing stimuli not only include the nursing stimulus, but light, audition, olfaction, and stress can serve a stimulatory role. Finally, although it is well known that dopamine of hypothalamic origin provides inhibitory control over the secretion of prolactin, other factors within the brain, pituitary gland, and peripheral organs have been shown to inhibit or stimulate prolactin secretion as well. It is the purpose of this review to provide a comprehensive survey of our current understanding of prolactin's function and its regulation and to expose some of the controversies still existing.

Effect of agonists and antagonists of cholinergic neurotransmission on growth hormone release in the dog

1983 ◽  
Vol 103 (1) ◽  
pp. 15-20 ◽  
Author(s):  
Felipe F. Casanueva ◽  
Roberto Betti ◽  
Silvano G. Cella ◽  
Eugenio E. Müller ◽  
Paolo Mantegazza
Keyword(s):  
Growth Hormone ◽  
Muscarinic Receptors ◽  
Nicotinic Receptors ◽  
Anticholinergic Drug ◽  
Complete Suppression ◽  
Butyl Bromide ◽  
Clear Cut ◽  
The Central Nervous System ◽  
Pre Treatment ◽  
Releasing Effect

Abstract. In unanaesthetized dogs iv administration of the cholinesterase inhibitor eserine (0.5 mg) or the cholinergic muscarinic receptor agonist oxotremorine (0.25 mg) induced a clear-cut rise in plasma canine growth hormone (cGH) levels. Complete suppression of the GH-releasing effect of eserine and oxotremorine was induced by blockade of cholinergic muscarinic receptors by atropine (80 or 20 μg/kg, 30 min before) but not by scopolamine-N-butyl bromide (0.8 mg/dog, 30 min before), an anticholinergic drug which does not cross the blood brain barrier (BBB). In contrast, activation of cholinergic nicotinic receptors by nicotine (6 mg) failed to alter resting cGH concentrations, and pre-treatment with the nicotinic receptor blocker mecamylamine (5 mg, 30 min before) did not counteract the GH-releasing effect of eserine. Other cholinomimetic drugs, e.g. pilocarpine, 4-aminopyridine, carbachol and bethanechol failed to induce a rise in plasma cGH concentrations. These data indicate that: 1) cholinergic muscarinic but not nicotinic receptors located in the central nervous system (CNS) inside the BBB play a facilitatory role in tonic cGH release; 2) pharmacologically distinct muscarinic receptors may exist in the CNS.

Paradoxical suppression of prolactin secretion: involvement of catecholaminergic mechanisms and the adrenal gland

1984 ◽  
Vol 105 (4) ◽  
pp. 463-467 ◽  
Author(s):  
Richard J. Krieg ◽  
Steven W.J. Lamberts ◽  
Robert M. MacLeod
Keyword(s):  
Adrenal Gland ◽  
Restraint Stress ◽  
Blocking Agent ◽  
Prolactin Secretion ◽  
Female Rats ◽  
Highly Sensitive ◽  
The Central Nervous System ◽  
Pre Treatment ◽  
Plasma Prl ◽  
Catecholaminergic Mechanisms

Abstract. Prolactin (Prl) secretion is normally elevated on the afternoon of pro-oestrus in the rat. Studies have shown that ether stress caused a 'paradoxical inhibiting effect' on these high Prl levels. The present study was designed to investigate whether the paradoxical suppression of Prl was mediated by the central nervous system or the adrenal glands. Plasma was obtained from adult female rats after sampling via intra-atrial catheters from 16.25–18.45 h on the afternoon of pro-oestrus. Restraint stress administered between 16.45–17.00 h induced the expected precipitous decrease in plasma Prl in intact animals. Pre-treatment of intact animals with the catecholamine receptor blocking agent haloperidol (1.0 mg/kg at 13.00 h) resulted in a further elevation of plasma Prl levels as compared with untreated controls, but eliminated the decrease of Prl in response to restraint stress. Although acutely adrenalectomized (ADX) animals proved to be highly sensitive to the bleeding procedures, initial Prl levels on the afternoon of pro-oestrus were not different from those of intact animals. Restraint stress under conditions of acute ADX was not found to induce the expected suppression of high Prl levels. Rather, the response was opposite to that which occurred in intact animals. These results indicate that the paradoxical suppression of Prl by restraint stress was mediated by catecholaminergic mechanisms, and that the adrenal gland was essential for the effect.

INFLUENCE OF ANAESTHETICS ON BASAL, PERPHENAZINE-INDUCED AND THYROTROPHIN RELEASING HORMONE-INDUCED PROLACTIN SECRETION IN OVARIECTOMIZED, OESTROGEN-TREATED RATS

1975 ◽  
Vol 66 (2) ◽  
pp. 151-157 ◽  
Author(s):  
D. M. LAWSON ◽  
R. R. GALA
Keyword(s):  
Central Nervous System ◽  
Anterior Pituitary ◽  
Chloral Hydrate ◽  
Direct Action ◽  
Prolactin Secretion ◽  
Thyrotrophin Releasing Hormone ◽  
Releasing Hormone ◽  
Site Of Action ◽  
The Central Nervous System ◽  
Normal Increase

SUMMARY Plasma levels of prolactin were determined, by radioimmunoassay, in ovariectomized, oestrogen-treated rats after administration of ether, sodium pentobarbitone, urethane, chloral hydrate or ketamine. These anaesthetics, when administered alone, induced sustained increases in the plasma level of prolactin (continuous ether inhalation), no change in prolactin secretion (urethane), or depressions in the level of prolactin (sodium pentobarbitone, chloral hydrate and ketamine). These same anaesthetics when given before perphenazine failed to alter the stimulatory effect of this phenothiazine on prolactin secretion. Sodium pentobarbitone did not alter the normal increase in prolactin concentration after intra-arterial administration of synthetic thyrotrophin releasing hormone (TRH). These results indicated that anaesthetics do not affect the response of either the central nervous system or the anterior pituitary to perphenazine or TRH although they affect prolactin secretion when administered alone. The site of action of anaesthetics must, therefore, be different from that of perphenazine or perphenazine must be capable of overcoming their influence by direct action on the pituitary.

Effect of [Asu,]eel calcitonin on prolactin release in normal subjects and patients with prolactinoma

1985 ◽  
Vol 108 (3) ◽  
pp. 297-304 ◽  
Author(s):  
Hidesuke Kaji ◽  
Kazuo Chihara ◽  
Naoto Minamitani ◽  
Hitoshi Kodama ◽  
Tetsuya Kita ◽  
...  
Keyword(s):  
Body Weight ◽  
Bolus Injection ◽  
Normal Subjects ◽  
Regular Insulin ◽  
Prolactin Release ◽  
Saline Administration ◽  
The Central Nervous System ◽  
Plasma Prl ◽  
Male Subjects

Abstract. The effect of [Asu]eel calcitonin (ECT), an equipotent analogue of eel CT, on prolactin (Prl) secretion was examined in 12 healthy male subjects and in 6 patients with prolactinoma. In healthy subjects, ECT (0.5 μg/kg body weight · h) or saline was infused for 2 h and TRH was injected iv as a bolus of 500 μg at 1 h of ECT or saline administration. ECT did not affect basal Prl levels during 1 h of infusion. TRH caused a significant increase of plasma Prl with peak values of 75.2 ± 11.6 ng/ml in ECT-infused subjects, which did not differ from those infused with saline (68.5 ± 8.3 ng/ml). Next, an iv bolus injection of regular insulin (0.1 U/kg body weight) was followed by an infusion of ECT or saline alone. Plasma Prl peaks after hypoglycaemic stress were significantly lower in ECT-infused subjects than those in saline-injected controls (ECT, 16.5 ± 3.1 vs 33.5 ± 9.6 ng/ml, P < 0.05). In patients with prolactinoma, basal levels of plasma Prl ranging from 42.0–4130 ng/ml failed to change during iv infusion of ECT. Moreover, ECT (10−9–10−6m) did not affect Prl release from prolactinoma tissues perifused in vitro. These findings suggest that ECT may not act directly on the pituitary to modify Prl release. Rather, peripherally administered ECT appears to suppress Prl release via the central nervous system.

Prolactin secretion and dopamine receptors of the MtTW15 transplantable pituitary tumour

1982 ◽  
Vol 94 (3) ◽  
pp. 347-NP ◽  
Author(s):  
M. J. Cronin ◽  
D. A. Keefer ◽  
C. A. Valdenegro ◽  
L. G. Dabney ◽  
R. M. MacLeod
Keyword(s):  
Pituitary Gland ◽  
Dopamine Receptors ◽  
Anterior Pituitary ◽  
Pituitary Tumour ◽  
Prolactin Secretion ◽  
Tumour Cells ◽  
Dopamine Antagonist ◽  
Cell Column ◽  
Prolactin Release

The MtTW15 transplantable pituitary tumour grown in rats was tested in vitro for the ability of dopamine agonists to affect prolactin secretion and for the existence of dopamine receptors. Prolactin release from enzymatically dispersed cells and non-enzymatically treated tissue fragments of both the tumour and the anterior pituitary gland was determined in a cell perifusion column apparatus. Dopamine (0·1–5 μmol/l), bromocriptine (50 nmol/l) and the dopamine antagonist haloperidol (100 nmol/l) had no effect on prolactin release from the tumour cells. In contrast, dopamine (500 nmol/l) inhibited prolactin secretion from normal anterior pituitary cells in a parallel cell column and haloperidol blocked this inhibition. Although oestrogen treatment in vivo stimulated prolactin release in vitro when the tumour was removed and studied in the cell column, oestrogen had no effect on the inability of dopamine to modify the prolactin secretion. Growth hormone release from the tumour cells was not affected by dopamine. Although MtTW15 cells were refractory to dopaminergic inhibition of prolactin release, the dopamine receptors present in tumour homogenates were indistinguishable from the dopamine receptors previously defined in the normal anterior pituitary gland. The binding of the dopamine antagonist [3H]spiperone to the tumour was saturable (110 fmol/mg protein), of high affinity to one apparent class of sites (dissociation constant = 0·12 nmol/l), reversible and sensitive to guanine nucleotides. The pharmacology of the binding was defined in competition studies with a large number of agonists and antagonists. From the order of potency of these agents, a dopaminergic interaction was apparent. We conclude that the prolactin-secreting MtTW15 tumour cells appear to be completely unresponsive to dopamine or to the potent dopamine agonist bromocriptine, in spite of apparently normal dopamine receptors in the tumour.

A COMPARISON OF THE EFFECTS OF FOUR ERGOT DERIVATIVES ON PROLACTIN SECRETION BY DISPERSED RAT PITUITARY CELLS

1980 ◽  
Vol 87 (1) ◽  
pp. 95-103 ◽  
Author(s):  
G. DELITALA ◽  
T. YEO ◽  
ASHLEY GROSSMAN ◽  
N. R. HATHWAY ◽  
G. M. BESSER
Keyword(s):  
Anterior Pituitary ◽  
Ergot Alkaloids ◽  
Prolactin Secretion ◽  
Pituitary Cells ◽  
Inhibitory Effects ◽  
Prolactin Release ◽  
Ergot Derivatives ◽  
Rat Pituitary ◽  
Rat Pituitary Cells

The inhibitory effects of dopamine and various ergot alkaloids on prolactin secretion were studied using continuously perfused columns of dispersed rat anterior pituitary cells. Bromocriptine (5 nmol/l) and lisuride hydrogen maleate (5 nmol/l) both inhibited prolactin secretion, the effects persisting for more than 3 h after the end of the administration of the drugs. A similar although less long-lasting effect was observed with lergotrile (50 nmol/l) and the new ergoline derivative, pergolide (5 nmol/l). These effects contrasted with the rapid disappearance of the action of dopamine. The potency estimates of the ergots relative to that of dopamine were: lergotrile, 2·3; bromocriptine, 13; lisuride, 15; pergolide, 23. The dopamine-receptor blocking drugs, metoclopramide and haloperidol, antagonized the prolactin release-inhibiting activity of the compounds; bromocriptine and lisuride showed the highest resistance to this dopaminergic blockade. The results suggested that the direct effect of the ergot derivatives on dispersed pituitary cells was mediated through dopamine receptors and emphasized the long-lasting action of bromocriptine and lisuride in vitro.

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