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R Collu

Publications and source records attributed to R Collu.

At least 37 records · Page 2Linked to original sources
PubMed1986

Inhibition of prolactin release and blockade of adenohypophyseal cell cyclic AMP accumulation are two dissociable effects of dopaminergic and non-dopaminergic drugs.

The secretion of PRL by the anterior pituitary gland is under a tonic inhibitory control exerted by dopamine (DA). However, the mechanism(s) involved in the inhibition of PRL secretion is not clearly defined. Several recently published papers supported the hypothesis that DA inhibits the release of PRL through blockade of the pituitary adenylate cyclase-cyclic AMP system. We have recently demonstrated that sodium ions are essential for dopaminergic inhibitory action on PRL secretion. The present paper reports the effects, in the presence or in the absence of Na+, of either DA, bromocriptine, apomorphine or 2 anticalmodulin drugs, penfluridol and W-7, on cyclic AMP accumulation by rat adenohypophyseal cells in primary culture. Studies with dopaminergic agonists show that in the presence of Na+ inhibition of both PRL and cyclic AMP is obtained at 15 and 30 min, while in the absence of the ion a dissociation exists between the inhibition of PRL release which is completely abolished, and that of cyclic AMP content which is still present. Dose-response studies done in the presence of Na+ show the existence of a good correlation between hormone and nucleotide effects of dopaminergic agonists while, in the absence of Na+, a dissociation is observed between the inhibition of PRL release, which is completely suppressed, and that of cyclic AMP accumulation which is slightly or not at all decreased. The inhibitory effects of penfluridol after 15 and 30 min of incubation were not suppressed by Na+ removal, although its hormonal actions were slightly decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

The Montreal Type A Intervention Project: major findings.

This article reports a comparison of three short-term treatments (aerobic exercise, cognitive-behavioral stress management, and weight training) in modifying behavioral and cardiovascular reactivity to laboratory psychosocial stressors in healthy Type A men. One hundred seven men completed the treatments and evaluations, 33 in the aerobic exercise group, and 37 each in the cognitive-behavioral stress management and weight-training groups. The stress management group showed significantly greater changes in behavioral reactivity (reductions of 13% to 23% below initial values) than the two physical exercise groups, which did not differ significantly from each other. For physiological reactivity, changes attributable to intervention were trivial for all three treatment groups. The positive finding of reduced behavioral reactivity as a result of the stress management intervention is of potential clinical significance and warrants further exploration. The lack of meaningful reductions in physiological reactivity also requires further exploration in that it raises questions concerning the ability of behavioral treatments in general to modify physiological reactivity, the ability of existing measures to assess accurately changes that are produced and, most fundamental of all, the relevance of physiological reactivity as an outcome measure for treatment efforts with Type As.

Adaptation, Psychological↗
PubMed1986

Solubilization and characterization of D2-dopamine receptors in an estrone-induced, prolactin-secreting rat pituitary adenoma.

D2-dopamine (3,4-dihydroxyphenylethylamine) receptors were successfully solubilized with 3-[(3-cholamidopropyl)-dimethylammonio]-1-propane sulfonate from an estrone-induced rat pituitary adenoma. Forty-five percent of initial protein and 48% of initial [3H]spiroperidol binding sites were solubilized. The high affinity as well as the stereoselectivity of the sites was preserved. The order of potency of dopaminergic agonists was found to be typical of D2 receptors. Target size analysis by radiation inactivation indicated a molecular weight of 143,000 +/- 3,000 and of 106,000 +/- 4,000 daltons for membrane-bound and solubilized receptors, respectively. This suggests the loss of a 37,000-dalton subunit during solubilization without significant modification of binding characteristics. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of receptor protein preparation photolabeled with N-(p-azido-m[125I]iodophenethyl)spiroperidol confirmed the existence of a 94,000-dalton peptide which probably constitutes the ligand binding site of the receptor. Thus, our data indicate that chronic estrogen treatment of rats, although inducing a pituitary adenoma, does not modify the pharmacological characteristics of D2 receptors. These data suggest therefore that these adenoma may represent an ideal source of material for further biochemical characterization of D2 receptors.

Adenoma↗
PubMed1986

Role of calcium and sodium ions in the inhibitory control of baseline and stimulated prolactin release.

The mechanism of dopamine (DA) inhibition of pituitary PRL release is still unclear. To study it, we utilized enzymatically dispersed anterior pituitary cells obtained from adult female Sprague-Dawley rats. The cells were incubated in media with or without Na+ and in the presence or the absence of various drugs for 30 min for evaluating the secretion of PRL under baseline and experimental conditions. In some experiments, 45Ca2+ (1 microCi/ml) was added after 30 min of incubation and the latter prolonged for an additional minute to determine Ca2+ uptake. DA inhibited baseline PRL release and 45Ca2+ uptake in a dose-dependent manner only in the presence of Na+ and was totally inactive in its absence. The inhibitory effects of Nifedipine and Nicardipine, two Ca2+ channel antagonists, on PRL release were also found to be Na+ dependent. BAY K 8644, a Ca2+ channel agonist, stimulated PRL release and Ca2+ uptake in a dose-dependent manner, and these effects were enhanced by Na+-free media. DA antagonized the stimulatory actions of BAY K 8644 on PRL release in a similar dose-dependent manner both in the presence and the absence of Na+. However, on stimulated 45Ca2+ uptake DA was less effective in the absence of Na+. The stimulatory action of TRH on PRL release was enhanced by the absence of Na+. DA antagonized the effect of TRH in a dose-dependent manner both in the presence and in the absence of Na+ but appeared more effective in the absence of the ion. The PRL-releasing effects of phorbol ester and of the Ca2+ ionophore A23187 were antagonized by DA in a Na+- independent manner. These results suggest the existence of two mechanisms of DA inhibitory action: one exerted on baseline PRL release which is Na+ dependent, receptor linked, and probably implicates potential operated Ca2+ channels; the other is exerted on stimulated PRL release, is Na+ independent, and appears to be a postreceptorial intracellular event probably involving protein kinase C and/or cytosolic Ca2+ levels.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1986

Isolation, purification and culture of Sertoli cells from immature piglet testes.

Several studies suggest a role of Sertoli cells in the control of Leydig cell steroidogenesis. In order to verify this hypothesis, we have developed a system for the purification of pig Sertoli cells. These cells were then characterized by their morphological appearance in light and electron microscopy, their ability to bind [125I]follicle stimulating hormone (FSH) and their functional capacity as evaluated by adenosine 3',5' monophosphate (cAMP) accumulation and lactate production when in primary culture under basal and FSH-stimulated conditions. Crude Sertoli cell suspensions from immature porcine testes were fractionated on discontinuous Percoll gradients (densities 1.025, 1.039, 1.055, 1.080 g/ml). Highly purified Sertoli cells were contained in the second band (d: 1.039) generated on the gradient. These cells demonstrated morphological and functional integrity as evidenced by binding specifically [125I] FSH and by responding to FSH stimulation (by an increased production of cAMP and lactate after 3 days in primary culture), but not to human chorionic gonadotrophin (hCG). This preparation represents a useful model for the study of Sertoli cell functions and their interation with Leydig cells in the regulation of testicular steroidogenesis.

Animals↗
PubMed1985

Gastric hypersecretion by intracisternal TRH: dissociation from hypophysiotropic activity and role of central catecholamine.

Intracisternal injection of the TRH analogs, MK 771 (0.01-1 micrograms) or A 3475 [pGlu-His-(1,3'-dicarboxymethyl)-Pro-NH2] (0.1-1 micrograms), dose-dependently stimulated gastric acid secretion in pylorus-ligated rats although A 43475 was devoid of TSH-releasing activity by cultured anterior pituitary cells. Depletion of brain catecholamine by combined administration of the neurotoxic agent, 6-hydroxydopamine, and the catecholamine synthesis inhibitor, alpha-methyl-ptyrosine, completely abolished intracisternal TRH-induced stimulation of gastric secretion. Blockade of dopamine receptors by intracisternal haloperidol, peripheral depletion of catecholamine by chronic treatment with guanethidine combined with acute adrenalectomy or cervical cord transection at C5 level, did not modify gastric response to TRH. These results suggested that the stimulation of gastric secretion by intracisternal TRH is unrelated to its hypophysiotropic activity and required the integrity of central but not peripheral catecholaminergic system.

Animals↗
PubMed1985

Exaggerated psychophysiological reactivity: issues in quantification and reliability.

Marked physiological reactivity to challenging mental tasks has been associated with elevated risk for, as well as the presence of, coronary heart disease. However, little systematic enquiry into the reliability and quantification of such exaggerated reactivity has emerged. Subjects were 32 male, managerial employees, ranging in age from 22 to 56 yr, who satisfied the following criteria: no history or current signs of heart disease, presence of Type A behavior pattern as revealed by the Structured Interview, and an increase during an initial psychosocial stress testing of at least 25% over baseline in at least three out of five psychophysiological indices. Heart rate, systolic blood pressure, diastolic blood pressure, plasma epinephrine and plasma norepinephrine levels were monitored while challenging mental tasks were performed in three sessions (screening, pretraining and posttraining) spaced several weeks apart. Psychophysiological reactivity during the tasks emerged as a consistent trait. For all five measures, change scores from baseline during the screening session were significantly correlated with change scores during the pretraining session. Moreover, the magnitude of the change scores were similar in the screening and pretraining sessions. Analysis of cross correlations within and between indices provided little support for the use of data transformations such as residual scores or analysis of covariance. Finally, on four out of five measures, the challenging tasks were found to be comparable in the degree of reactivity elicited. These findings suggest that, for selected Type A men, exaggerated psychophysiological reactivity occurs reliably when monitored with multiple indices, appears insensitive to mere passage of time, and can be uniformly elicited by a variety of tasks.

Adult↗
PubMed1985

Dopaminergic activity of four analogs of butaclamol.

The displacing potency of four analogs of the neuroleptic drug butaclamol were evaluated using dog striatal tissue and [3H]-Spiroperidol as ligand. Although significantly less powerful than the parent compound, two of them (N-isobutyl butaclamol equatorial; N-methyl butaclamol equatorial) could be used for dopaminergic receptor studies.

Animals↗
PubMed1985

Presence of high affinity dopamine receptors in estrone-induced, prolactin-secreting rat pituitary adenomas: a model for human prolactinomas.

Adenomatous cells obtained from a pituitary tumor induced in Fisher 344/Lis rats by the subcutaneous implantation of estrone (E1) were found to secrete large amounts of prolactin (PRL). The secretion of PRL was stimulated by thyrotropin-releasing hormone (TRH) and low concentrations of dopamine (DA), while micromolar concentrations of DA were inhibitory. High affinity binding sites for 3H-spiroperidol (3H-SPIR) were found to be present on the cells and to conform to the criteria of dopaminergic receptors. An adenylate cyclase (AC) present in the cells could be activated by a guanyl nucleotide and was inhibited by DA in the presence of guanosine 5'-triphosphate (GTP). Fractionation of the adenomatous cells by Percoll gradients identified two groups of cells capable of secreting PRL and bearing 3H-SPIR binding sites. These data indicate that this rat pituitary adenoma may be a model for human prolactinomas that might be utilized for the study of the mechanism of action of dopaminergic drugs.

Adenoma↗
PubMed1985

Effects of chronic bromocriptine treatment of an estrone-induced, prolactin-secreting rat pituitary adenoma.

Bromocriptine (BROM), a dopamine (DA) agonist, is commonly and successfully used for long-term treatment of human prolactinomas. We have studied the effects of chronic BROM administration to female 344 Fisher/Lis rats bearing an estrone-induced, prolactin (PRL)-secreting pituitary tumor recently characterized as a model for human prolactinoma. The animals were injected twice daily with BROM (2.5 mg/kg) or with diluent. After 1 month of treatment, the animals were sacrificed, and plasma collected and stored at -20 degrees C for PRL radioimmunoassay. The pituitary tumors were removed and tumoral mammotrophs dispersed enzymatically for studies of DA receptor binding and PRL release in vitro. BROM treatment significantly reduced tumor weight, cell size, rough endoplasmic reticulum, Golgi complexes and plasma PRL levels. [3H]-spiroperidol binding to tumoral mammotrophs was also evaluated. BROM induced a significant decrease in the number of DA binding sites without any changes in affinity. These results indicate that chronic BROM treatment of an animal model of prolactinoma induces tumor involution, reduction of PRL release and probably synthesis, and down regulation of dopaminergic binding sites.

Adenoma↗
PubMed1984

Estrone-induced, prolactin-secreting and dopamine-sensitive rat pituitary tumor.

Prolactin (PRL)-secreting rat pituitary tumors were induced in female Fisher 344/Lis rats by s.c. implants of estrone (E1) pellets. Tumor growth was relatively fast and reached about 100 mg within 2 months. Ovariectomy at the time of E1 implants seemed to accelerate the growth of the tumors. Tumor cells in primary culture produced mainly PRL, while growth hormone (GH) release was about 2% of PRL production and the release of some other pituitary hormones did not exceed 1% of PRL values. Tumor cells were found to have high-affinity dopamine (DA) receptors. The addition of DA in vitro at 10(-10) M concentration stimulated PRL release, while at 10(-6) M concentration it inhibited the release of the hormone by more than 50% of control values. Histological, immunohistochemical and electron microscopical studies demonstrated the tumor to be composed mainly of maximally stimulated mammotrophs.

Animals↗
PubMed1984

Role of catecholamines in the inhibitory effect of immobilization stress on testosterone secretion in rats.

Immobilization stress applied for 6 h induced, in adult male rats, a rise of epinephrine (E) and norepinephrine (NE) plasma levels and a decrease of baseline plasma testosterone (T) values and of human chorionic gonadotropin (hCG)-induced T response. Treatment of the animals for 5 weeks with guanethidine (G), a sympathetic neuron toxic agent, significantly decreased E and NE responses to stress and partly antagonized the inhibitory effects exerted by immobilization on T biosynthesis. Adrenalectomy totally suppressed circulating E and reduced the stress-induced NE increase while partly antagonizing the inhibitory effects exerted on T biosynthesis. Combined G and adrenalectomy treatments totally suppressed plasma E and NE, and completely blocked the effects of immobilization on T levels. Treatment of the animals with the alpha 1-adrenergic blocker, prazosin, and the beta 1-adrenergic blocker, metoprolol, did not modify the effects of stress on T biosynthesis. Treatment with propranolol or with butoxamine, a nonspecific beta- and a specific beta 2-adrenergic receptor blocker, respectively, antagonized the testicular hyposensitivity to hCG induced by stress. Stress- or treatment-induced changes of plasma luteinizing hormone (LH) and hCG levels were not consistently correlated with plasma T modifications. These findings suggest that at least part of the inhibitory effects of immobilization stress on T biosynthesis is exerted by catecholamines through a beta 2-adrenergic receptor.

Adrenal Glands↗
PubMed1984

Effect of glucocorticoids on testosterone production by porcine Leydig cells in primary culture.

For this study, purified immature porcine Leydig cells in primary culture were used. After 2 days of culture, the cells were incubated with dexamethasone (5 X 10(-9), 1 X 10(-7) M) for various periods of time (3-45 h). The media were discarded and treatment was repeated with or without the addition of human chorionic gonadotropin (HCG, 10 mIU/mL) for 3 h. Dexamethasone (10(-7) M) decreased testosterone production of HCG-treated cells (up to 40%) in a time-dependent fashion while the lower dose was ineffective. The effect of varying doses (10(-8) and 10(-6) M) of natural glucocorticoids (corticosterone, cortisol) or synthetic glucocorticoids (triamcinolone, triamcinolone acetonide, betamethasone, dexamethasone) and that of a synthetic progestin (R-5020) on cultured Leydig cells was also studied. After 18 h of preincubation, the various synthetic but not the natural steroids nor R-5020, were able to decrease testosterone production of control and HCG-treated cells by 20-40%. Of a number of other hormonal and nonhormonal substances studied at concentrations of 10(-9)-10(-5) M, only lysine8-vasopressin at a concentration of 10(-6) M was able to inhibit testosterone production by these cells. These results indicate that dexamethasone and other synthetic glucocorticoids, and to a lesser degree lysine8-vasopressin, may exert a direct inhibitory effect on testosterone production by purified porcine immature Leydig cells in vitro.

Animals↗
PubMed1984

The 3 beta-hydroxysteroid dehydrogenase activity of cultured porcine Leydig cells in primary culture.

Previous studies have shown that there is a spontaneous progressive increase in human chorionic gonadotropin (HCG)-stimulated testosterone (T) production by immature porcine Leydig cells during primary culture for 3 days, whereas basal T production is unaltered. Preliminary data indicated that during this time, there was an increase in the activity of the 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD). The purpose of the present study was to further characterize this increase. 3 beta-HSD was assayed by measuring the conversion of tritiated dehydroepiandrosterone (DHEA) to androstenedione in the presence of NAD+. A ninefold increase in activity occurred between days 1 and 2 and only twofold between days 2 and 3. A 5- to 20-fold increase of the apparent maximum velocity of the enzyme was observed after 3 days of culture while the apparent Km remained unchanged. Cycloheximide treatment (150 ng/mL) completely abolished this spontaneous increase in enzyme activity. In parallel experiments, the stimulatory effect of HCG on T and DHEA production was inhibited by cycloheximide treatment by 90% and 60%, respectively, whereas basal T production was not affected. These results suggest that the spontaneous increase of 3 beta-HSD activity in primary cultures of porcine Leydig cells is secondary to de novo protein synthesis and that this phenomenon may be partially responsible for the increased responsiveness of these cells to HCG during the culture period.

3-Hydroxysteroid Dehydrogenases↗
PubMed1984

Dopaminergic binding sites in human pituitary adenomas other than prolactinomas.

Binding studies of [3H]-spiroperidol, a potent dopamine antagonist, were performed on dispersed cells obtained from 2 mixed PRL- and GH-secreting adenomas, 3 GH-secreting adenomas and 4 'nonsecreting' pituitary tumors. Saturable, high affinity binding sites for [3H]-spiroperidol were identified in the two adenomas of mixed PRL and GH secretion, in 2 of 3 GH-secreting adenomas and in 2 of 4 'nonsecreting' adenomas. These data indicate that dopaminergic binding sites are present in some GH-secreting adenomas in the absence of PRL hypersecretion and in some 'nonsecreting' pituitary adenomas.

Adenoma↗
PubMed1984

Interaction of sulpiride with human pituitary dopaminergic receptors is sodium dependent.

The effects of various drugs on [3H]-spiroperidol binding to human anterior pituitary and prolactinoma membranes are studied in the presence and in the absence of sodium chloride in the incubation medium. It is shown that in the absence of NaCl, 1-sulpiride is significantly less potent in displacing the radioactive ligand from its dopaminergic binding sites than in the presence of NaCl. On the contrary, the interaction of neuroleptics (d-butaclamol and haloperidol) and dopamine agonists (apomorphine and bromocriptine) was unaffected by the NaCl conditions.

Binding, Competitive↗
PubMed1984

Sodium ions: their role and mechanism of action in the control of prolactin release.

The secretion of PRL by the pituitary gland is under a tonic inhibitory control exerted by dopamine. However, the mechanisms involved in this inhibition remain to be completely defined. We have investigated the effects of sodium removal in the incubation medium on baseline PRL, on the inhibitory effects exerted by bromocriptine, haloperidol and cobalt, and on the stimulatory action of TRH and vasoactive intestinal polypeptide (VIP) on PRL release by enzymatically dispersed rat anterior pituitary cells in primary culture. The effects of ouabain, tetrodotoxin, and veratridine on baseline PRL release and on the inhibitory effects of dopaminergic agents were also investigated. Basal PRL release was slightly but significantly reduced by replacing sodium by choline in the incubation medium and was almost completely suppressed when isoosmolar concentrations of glucose were substituted for sodium. On the other hand, ouabain slightly but significantly increased basal release of the hormone. In the absence of sodium, the dose-dependent inhibitory effect of bromocriptine was greatly reduced. Of two antidopaminergic drugs, haloperidol and l-sulpiride, only the first inhibited the release of PRL at high doses (10(-5) - 10(-4) M) in the presence of sodium but became stimulatory at 10(-4) M in the absence of the ion. Ouabain, tetrodotoxin, and veratridine failed to significantly modify the inhibitory effects of either dopamine or bromocriptine. The dose-dependent inhibitory effects of cobalt and the releasing actions of TRH and VIP were not significantly influence by sodium removal from the incubation medium, although VIP appeared to be active at a lower concentration in the absence of the ion. These data indicate that, although the presence of a normal ionic charge in the incubation medium is essential for the baseline secretion of PRL, sodium ions specifically play only a minor role in a phenomenon which is essentially Ca2+-dependent. They also clearly show that sodium intervenes in dopaminergic agonist and antagonist inhibition of PRL release through a mechanism which appears independent of either dopaminergic receptor, Ca2+ or Na+ channel, or Na+/K+ pump. It is hypothesized that a normal intracellular sodium concentration is essential for dopaminergic agonist or antagonist inhibitory action.

Animals↗