Pertussis toxin uncouples dopamine agonist inhibition of prolactin release

1983 ◽  
Vol 244 (5) ◽  
pp. E499-E504 ◽  
Author(s):  
M. J. Cronin ◽  
G. A. Myers ◽  
R. M. MacLeod ◽  
E. L. Hewlett
Keyword(s):  
Cyclic Amp ◽  
Dopamine Agonist ◽  
Pertussis Toxin ◽  
Anterior Pituitary ◽  
Prolactin Secretion ◽  
Pituitary Cells ◽  
Prolactin Release ◽  
Pituitary Prolactin ◽  
Hormone System

Pertussis toxin, a protein exotoxin produced by Bordetella pertussis, markedly reduced or eliminated the ability of dopamine or the dopamine agonist bromocriptine to inhibit prolactin release from anterior pituitary cells in vitro. Toxin-mediated reversal of the effect on dopamine agonist inhibition of prolactin release occurred with a lag of greater than 6 h, was maximal by 24 h, and persisted for at least 6 days after removal of the toxin from the medium. The toxin reduced dopamine agonist efficacy without altering potency or directly modifying the dopamine receptor (as measured by [3H]spiperone binding). The ability of dopamine to reduce cellular cyclic AMP content was also antagonized by pertussis toxin, supporting the hypothesis that reduction of cellular cyclic AMP content and inhibition of prolactin secretion may be causally related. These data demonstrated that pertussis toxin can prevent the typical inhibitory action of dopamine agonists on anterior pituitary prolactin release and suggest that this receptor-mediated inhibitory hormone system is analogous to other inhibitory receptors coupled to adenylate cyclase.

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.

Direct effect of adenosine on prolactin secretion at the level of the single rat lactotroph: involvement of pertussis toxin-sensitive and -insensitive transducing mechanisms

1993 ◽  
Vol 11 (3) ◽  
pp. 325-334 ◽  
Author(s):  
A Scorziello ◽  
E Landolfi ◽  
M Grimaldi ◽  
O Meucci ◽  
C Ventra ◽  
...  
Keyword(s):  
Adenylate Cyclase ◽  
Phospholipase C ◽  
G Protein ◽  
Pertussis Toxin ◽  
Anterior Pituitary ◽  
Prolactin Secretion ◽  
Catalytic Subunit ◽  
Pituitary Cells ◽  
Prolactin Release ◽  
Anterior Pituitary Cells

ABSTRACT We studied the effect of adenosine on prolactin secretion by the anterior pituitary, and the transduction mechanisms whereby the purine exerts its action. Adenosine inhibited prolactin release in basal and in vasoactive intestinal peptide (VIP)- or TRH-stimulated conditions. Pertussis toxin pretreatment reduced the inhibition of VIP-stimulated prolactin secretion which was induced by adenosine, while it completely abolished the effect of the purine on TRH-evoked prolactin release. In membrane preparations of anterior pituitary cells, adenosine reduced the adenylate cyclase activity stimulated by VIP. Such an inhibition was not blocked by pertussis toxin pretreatment. Furthermore, the purine reduced TRH-stimulated inositol phosphate production in cultured anterior pituitary cells, an effect that was reversed by pretreatment with pertussis toxin. In addition, the nucleoside did not significantly affect the TRH-induced rise in intracellular calcium. In conclusion, our data show that adenosine inhibits prolactin secretion, acting on purinergic receptors coupled to the adenylate cyclase enzyme and phospholipase C. The effect of the nucleoside on adenylate cyclase seems to be achieved either by the involvement of an adenosine receptor coupled to the catalytic subunit of the enzyme via a pertussis toxin-sensitive G protein, or by the activation of a site directly coupled to the catalytic subunit of the adenylate cyclase (the P site). Its effect on phospholipase C seems to be mediated by a purinergic receptor coupled to the intracellular effector via a pertussis toxin-sensitive G protein.

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.

scholarly journals In Vivo and In Vitro Arsenic Exposition Induces Oxidative Stress in Anterior Pituitary Gland

2016 ◽  
Vol 35 (4) ◽  
pp. 463-475 ◽  
Author(s):  
Sonia A. Ronchetti ◽  
María S. Bianchi ◽  
Beatriz H. Duvilanski ◽  
Jimena P. Cabilla
Keyword(s):  
Oxidative Stress ◽  
Pituitary Gland ◽  
Anterior Pituitary ◽  
Inorganic Arsenic ◽  
Anterior Pituitary Gland ◽  
Pituitary Cells ◽  
Prolactin Release ◽  
Stress Responsive Genes

Inorganic arsenic (iAs) is at the top of toxic metalloids. Inorganic arsenic-contaminated water consumption is one of the greatest environmental health threats worldwide. Human iAs exposure has been associated with cancers of several organs, neurological disorders, and reproductive problems. Nevertheless, there are no reports describing how iAs affects the anterior pituitary gland. The aim of this study was to investigate the mechanisms involved in iAs-mediated anterior pituitary toxicity both in vivo and in vitro. We showed that iAs administration (from 5 to 100 ppm) to male rats through drinking water increased messenger RNA expression of several oxidative stress-responsive genes in the anterior pituitary gland. Serum prolactin levels diminished, whereas luteinizing hormone (LH) levels were only affected at the higher dose tested. In anterior pituitary cells in culture, 25 µmol/L iAs significantly decreased prolactin release in a time-dependent fashion, whereas LH levels remained unaltered. Cell viability was significantly reduced mainly by apoptosis evidenced by morphological and phosphatidylserine externalization studies. This process is characterized by early depolarization of mitochondrial membrane potential and increased levels of reactive oxygen species. Expression of some key oxidative stress-responsive genes, such as heme oxygenase-1 and metallothionein-1, was also stimulated by iAs exposure. The antioxidant N-acetyl cysteine prevented iAs-induced effects on the expression of oxidative stress markers, prolactin release, and apoptosis. In summary, the present work demonstrates for the first time that iAs reduces prolactin release both in vivo and in vitro and induces apoptosis in anterior pituitary cells, possibly resulting from imbalanced cellular redox status.

Inhibitory effects of fumagillin and its analogue TNP-470 on the function, morphology and angiogenesis of an oestrogen-induced prolactinoma in Fischer 344 rats

1996 ◽  
Vol 150 (1) ◽  
pp. 99-106 ◽  
Author(s):  
H Stępień ◽  
M Grochal ◽  
K W Zieliński ◽  
S Mucha ◽  
J Kunert-Radek ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Anterior Pituitary ◽  
Angiogenesis Inhibitors ◽  
Prolactin Secretion ◽  
Prolonged Treatment ◽  
Endothelial Cell Proliferation ◽  
Pituitary Cells ◽  
Fischer 344 ◽  
F344 Rats

Abstract The process of angiogenesis occurs in many physiological states, but it is also essential for the growth of solid tumours and metastasis formation. An abnormal arterial vascularization has been shown in prolactin-secreting pituitary adenomas induced by prolonged treatment with oestrogens in Fischer 344 (F344) rats. It is thought that anti-angiogenic agents might be useful in therapy for these tumours. Fumagillin and its analogue TNP-470 are known to inhibit endothelial cell proliferation selectively, but their effect on lactotroph cell secretory function and prolactinoma formation has not yet been described. The aim of the present study was to examine the effects of fumagillin and TNP-470 on prolactin secretion, and morphological and vascular changes within the anterior pituitary in long-term oestrogen-treated male F344 rats in vivo and in vitro. As expected, 7 weeks after s.c. implantation of Silastic tubes containing 10 mg diethylstilboestrol (DES), a very high rise in serum prolactin levels was found. Both angiogenesis inhibitors injected s.c. at doses of 10 mg/kg body weight for 24 days attenuated the stimulatory effect of DES on prolactin production and release. They also diminished prolactin cell density and inhibited cell proliferation expressed as the number of anterior pituitary cells labelled with bromodeoxyuridine (BrdU), but the effect of TNP-470 was minor compared with fumagillin. Both angioinhibitors suppressed neovascularization within the anterior pituitary with similar potency but, on the other hand, they did not affect DES-induced increases in prolactin secretion from cultured rat pituitary cells and cell proliferation in vitro. In conclusion, our results provide strong evidence for the anti-tumour and anti-prolactin activity of angiogenesis inhibitors in the experimentally oestrogen-induced pituitary adenoma; this might be mediated indirectly through the inhibition of angiogenesis. Journal of Endocrinology (1996) 150, 99–106

Adenosine and its analogue ( − )-N6-R-phenyl-isopropyladenosine modulate anterior pituitary adenylate cyclase activity and prolactin secretion in the rat

1990 ◽  
Vol 5 (1) ◽  
pp. 69-76 ◽  
Author(s):  
G. Schettini ◽  
E. Landolfi ◽  
O. Meucci ◽  
T. Florio ◽  
M. Grimaldi ◽  
...  
Keyword(s):  
Adenylate Cyclase ◽  
Anterior Pituitary ◽  
Primary Cultures ◽  
Prolactin Secretion ◽  
Cyclase Activity ◽  
Adenylate Cyclase Activity ◽  
Pituitary Cells ◽  
Prolactin Release ◽  
Low Concentrations ◽  
High Concentrations

ABSTRACT The effect of adenosine and its analogue ( − )-N6-R-phenylisopropyladenosine (PIA) on both anterior pituitary adenylate cyclase activity and prolactin secretion was examined in the rat. Adenosine inhibited basal adenylate cyclase activity in a dose-dependent manner and also reduced the stimulation of the enzyme by vasoactive intestinal peptide (VIP). Likewise, in primary cultures of anterior pituitary cells, adenosine decreased prolactin secretion in both basal and VIP-stimulated conditions. In perifusion experiments, adenosine also inhibited prolactin release in both basal and TRH-stimulated conditions. PIA produced a biphasic pattern of response of basal adenylate cyclase activity, being inhibitory at low and stimulatory at high concentrations. In VIP-stimulated conditions, low concentrations of PIA inhibited both adenylate cyclase activity and prolactin release from primary cultures of pituitary cells, while no additive stimulatory effect was seen at high concentrations. Similarly, low concentrations of PIA reduced both basal and TRH-stimulated prolactin release from perifused pituitaries, while increasing PIA concentrations restored prolactin release. These data show that adenosine affects basal and stimulated prolactin secretion from anterior pituitary cells. Adenosine receptors seem to be coupled to the adenylate cyclase system in the anterior pituitary gland, suggesting a possible relationship between the effect of adenosine on adenylate cyclase activity and prolactin secretion.

In vitro inhibition of pituitary prolactin synthesis and release by hypothalamic extract

1963 ◽  
Vol 205 (2) ◽  
pp. 213-218 ◽  
Author(s):  
P. K. Talwalker ◽  
A. Ratner ◽  
J. Meites
Keyword(s):  
Cerebral Cortex ◽  
Anterior Pituitary ◽  
Acid Extract ◽  
Prolactin Release ◽  
Lysine Vasopressin ◽  
In Vitro Inhibition ◽  
Hormone Inactivation ◽  
Prolactin Synthesis ◽  
Pituitary Prolactin

When rat anterior pituitary (AP) was incubated at 37.5 C in a Dubnoff metabolic shaker for 2 hr, 169% more prolactin was found in the combined medium and AP than in nonincubated AP. When AP was incubated together with homogenate or acid extract of rat hypothalamus, prolactin levels in the medium and AP were markedly decreased (36–75%), indicating inhibition of synthesis and release. Acid extract of rat cerebral cortex had no effect on prolactin synthesis or release. Incubation of ovine or rat prolactin, with or without hypothalamus, did not decrease prolactin activity, demonstrating that hypothalamic inhibition of AP prolactin production was not due to hormone inactivation. Acetylcholine, epinephrine, norepinephrine, serotonin, histamine, substance P, oxytocin, and arginine or lysine vasopressin had no effect on AP prolactin release. These results indicate that the hypothalamus contains a factor(s) which inhibits synthesis and release of prolactin by the rat AP in vitro, and this factor(s) is not any of the recognized neurohumors in the hypothalamus.

STIMULATION OF PROSTAGLANDIN ACCUMULATION IN THE RAT ANTERIOR PITUITARY GLAND BY LUTEINIZING HORMONE RELEASING HORMONE IN VITRO

1977 ◽  
Vol 75 (2) ◽  
pp. 277-283 ◽  
Author(s):  
N. BARDEN ◽  
A. BETTERIDGE
Keyword(s):  
Luteinizing Hormone ◽  
Cyclic Amp ◽  
Anterior Pituitary ◽  
Pituitary Cells ◽  
Luteinizing Hormone Releasing Hormone ◽  
Releasing Hormone ◽  
Lh Release ◽  
Lh Rh ◽  
Stimulation Of

The addition of luteinizing hormone releasing hormone (LH-RH) to cultures of monolayers of rat anterior pituitary cells was shown to increase both the concentrations of prostaglandins E1 and E2 (PGE) in the cells and the release of LH over similar ranges of concentrations of LH-RH (10−6 to 10−10 mol/l). The peak concentration of PGE was observed after 2·5 h. The stimulation of the level of PGE in the cells by LH-RH was completely inhibited by two inhibitors of prostaglandin synthetase, which only partially inhibited the stimulation of LH release. Therefore the increased concentration of PGE was not obligatory for the effect of LH-RH on LH release. It was also shown that monobutyryl cyclic AMP stimulated the intracellular concentration of PGE and it is suggested that the stimulation of PGE levels may be mediated by increased levels of cyclic AMP in the cells after the addition of LH-RH.

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