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F Labrie

Publications and source records attributed to F Labrie.

At least 505 records · Page 28Linked to original sources
PubMed1982

Effect of chronic treatment with [D-Ala6, des-Gly-NH210]LHRH ethylamide on ovarian histology in the rat.

The effect of chronic treatment with the LHRH agonist [D-Ala6, des-Gly-NH210]LHRH ethylamide (LHRH-A) on ovarian histology was studied in adult female rats injected with 5 micrograms of the peptide, once every second day, for 0, 2, 4 or 8 weeks. Using light microscopy, we examined the number of small medium, large and atretic follicles, as well as the number of normal and regressing corpora lutea. Using the point-counting method, we measured the relative surface occupied by luteal cells. It was found that treatment with LHRH-A for up to 8 weeks led to no significant change in any of the parameters studied. Moreover, resumed meiotic maturation of an abnormally high number of atypical fragmentations of the ova could not be observed. At least at the dose used, the LHRH agonist does not appear to induce any histological alteration in ovarian morphology and supports the potential clinical use of LHRH agonists as a new approach in female contraception and for the treatment of estrogen-dependent pathologies.

Animals↗
PubMed1982

Comparative effects of LHRH agonist and ovine LH administration on testicular steroidogenesis in intact adult rat.

In order to better understand the effects of LHRH administration on testicular function in adult rat, we compared the inhibitory effects of LH and LHRH analogue [D-Ser-(TBU)6, des-Gly-NH2(10)]LHRH ethylamide upon testicular steroidogenesis and LH, FSH and prolactin receptor contents. Administration of LH as well as LHRH analogue resulted in a marked decrease of LH receptor levels, accompanied by a blockage at the level of 17-hydroxylase activity. We have been able to demonstrate that multiple LH administration can achieve a testicular desensitization comparable to that observed after LHRH agonist treatment.

Animals↗
PubMed1982

Distribution of luteinizing hormone-releasing hormone receptors in the rat ovary.

The distribution of luteinizing hormone-releasing hormone (LHRH) receptors was studied in the adult rat ovary using autoradiography after injection of the stable LHRH agonist 125I-labelled [D-Ser(TBU)6,des-Gly-NH2(10)]LHRH ethylamide (Buserelin) and by radioreceptor assay using the same tracer. In intact cycling female rats, no differences in ovarian LHRH receptor levels could be observed between day diestrus I and day proestrus. Moreover, similar levels are observed in total ovarian homogenate, corpora lutea and the remaining ovarian tissue in adult animals treated with PMSG (pregnant mare's serum gonadotropins) and hCG (human chorionic gonadotropin). Radioautographic data show a comparable distribution of grains over theca interna and externa, granulosa and luteal cells. The present findings indicate the presence of LHRH receptors in both the interstitial and follicular cells throughout all stages of cellular differentiation.

Animals↗
PubMed1982

Sensitivity of pituitary and corpus luteum responses to single intranasal administration of (D-ser[TBU]6-des-gly-NH2(10)) luteinizing hormone-releasing hormone ethylamide (Buserelin) in normal women.

We have previously shown that intranasal administration of Buserelin (Hoechst AG, Frankfurt, Germany) at mid-luteal phase inhibits progesterone secretion and shortens the luteal phase. In order to determine the best possible use of this medication, we studied the effect of increasing doses (50 to 1500 microgram) of the luteinizing hormone-releasing hormone (LH-RH) agonist administered between days 6 and 12 after the luteinizing hormone (LH) peak on the pituitary response and corpus luteum function. A near-maximal gonadotropin response was obtained at a dose of 200 microgram. Maximal LH stimulation was observed at 4 hours, and serum levels of the hormone remained elevated for at least 14 hours at the two highest doses. Maximal serum follicle-stimulating hormone (FSH) levels were usually observed 2 hours later than for LH, and the response was longer lasting. A 2- to 2.5-fold stimulating of serum progesterone levels was observed at 8 hours for all doses studied. There was a tendency for a dose effect on serum estradiol levels, a 2-fold stimulation being obtained at 14 hours at the highest dose of LH-RH analog. Up to 200 microgram, there was no apparent change in the luteal phase. At the 500-microgram dose, there was a clear tendency for decreased estradiol and progesterone concentrations during the treatment cycle, while at 1000 and 1500-microgram doses steroid levels were clearly inhibited and the luteal phase was shortened by 2.5 days. Posttreatment cycles were normal. Thus the corpus luteum is sensitive to a single high intranasal dose of Buserelin, the luteolytic effect being related to the prolonged gonadotropin response.

Administration, Intranasal↗
PubMed1982

Inhibition of serum androgen levels by chronic intranasal and subcutaneous administration of a potent luteinizing hormone-releasing hormone (LH-RH) agonist in adult men.

The effect of chronic treatment with the luteinizing hormone-releasing hormone (LH-RH) agonist Buserelin (Hoechst AG, Frankfurt/Main, West Germany) ([D-Ser(TBU)6,des-Gly-NH2(10)]LH-RH ethylamide) administrered by nasal spray (200 or 500 micrograms, twice daily) or subcutaneously (50 micrograms daily) for periods of 1 to 8 months was studied on serum sex steroids and LH levels in 18 patients with cancer of the prostate. Basal serum testosterone concentration decreases to 71.1 +/- 18.3 (NS) and 28.6 +/- 9.3%, (P less than 0.01) of control in patients receiving the 200-micrograms and 500-micrograms dose by nasal spray, respectively. In patients treated subcutaneously, a more rapid inhibition of serum testosterone levels to 19.6 +/- 6.4% of control (P less than 0.01) is observed. The finding of decreased levels of 17-OH-progesterone, testosterone, and dihydrotestosterone in the presence of unchanged pregnenolone concentration indicates that the decrease in androgen biosynthesis induced by Buserelin treatment is due to a blockage at the level of 17-hydroxylase and 17,20-desmolase activities. The present data indicate that chronic administration of Buserelin could be a safe and effective means of reducing serum androgens in patients with cancer of the prostate.

Administration, Intranasal↗
PubMed1982

Prolactin and estradiol increase striatal dopamine receptor density in intact, castrated and hypophysectomized rats.

1. Ovariectomized female or intact male rats were implanted with three adenohypophyses under the kidney capsule or treated with 17 beta-estradiol (10 micrograms twice daily) for 2 weeks. 2. In animals of both sexes, the pituitary-implanted and estradiol-treated rats had elevated plasma prolactin levels and had increased levels of striatal dopamine receptors. 3. We next investigated the possibility of an indirect action of estradiol via prolactin using hypophysectomized female rats (hypox) treated with 17 beta-estradiol or ovine prolactin (500 micrograms, twice daily) for 5 days. 4. Striatal dopamine receptor concentration was lower in hypox animals as compared to ovariectomized (85%, p less than 0.05) or intact female rats at random stage of the estrous cycle (76%, p less than 0.05) while the affinity (KD) of [3H]spiperone for these dopaminergic sites remained unchanged. 5. Treatment with estradiol or prolactin increased the level of striatal dopamine receptors (HYPOX + estradiol: 144% vs HYPOX, p less than 0.05; HYPOX + prolactin: 147% vs HYPOX, p less than 0.05). 6. These results indicate that high prolactin levels induced by pituitary implants or by injections of ovine prolactin lead, as observed with chronic estradiol treatment, to an increased density of striatal dopamine receptors. However, the effect of estradiol may not be explained exclusively by increased prolactin levels since the supersensitivity is also observed in hypophysectomized animals.

Animals↗
PubMed1982

beta-Adrenergic, CRF-ergic and dopaminergic mechanisms controlling alpha-MSH secretion in rat pars intermedia cells in primary culture.

1. A pure population of pars intermedia cells in primary culture was used to study changes in alpha-MSH secretion and cyclic AMP accumulation. 2. Beta-adrenergic agonists and CRF (corticotropin-releasing factor) stimulate alpha-MSH secretion and cyclic AMP accumulation. 3. Dopaminergic agonists inhibit basal as well as (-)isoproterenol- and CRF-induced alpha-MSH secretion and cyclic AMP accumulation. 4. Beta-adrenergic, dopaminergic and CRF receptors regulate pars intermedia cell activity probably through the adenylate cyclase system.

Adrenocorticotropic Hormone↗
PubMed1982

Estradiol, TRH and striatal dopaminergic mechanisms.

1. Estrogens have been shown to decrease the effect of apomorphine in a variety of animal behavioral models reflecting the sensitivity of striatal and mesolimbic dopamine receptors. 2. These include circling, and locomotor activity, in rats and suppression of midbrain tremor as well as lingual dyskinesia in monkeys. 3. Estradiol also increases the haloperidol-induced catalepsy in rats. Moreover estradiol increases 3H spiroperidol specific binding in the rat striatum and potentiates the increase caused by haloperidol or denervation with 6-hydroxydopamine. 4. These findings point to an action of estradiol similar to a week neuroleptic. 5. Thyrotropin-releasing hormone when injected into the head of the caudate nucleus in cats induces a head turning response which may be ipsilateral or contralateral depending upon the injection site. The response is similar to the effect of dopamine injected into the same site. 6. The effect of dopamine but not that of TRH is blocked by prior administration of haloperidol indicating that although TRH has a dopamine-like action in the caudate nucleus, it is not mediated via the dopamine terminals or the dopamine receptors.

Animals↗
PubMed1982

Stimulation of cyclic AMP accumulation and corticotropin release by synthetic ovine corticotropin-releasing factor in rat anterior pituitary cells: site of glucocorticoid action.

A 2.5-fold stimulation of cyclic AMP cellular content is measured 60 sec after addition of 100 nM synthetic ovine corticotropin-releasing factor (C-RF; corticoliberin) to rat anterior pituitary cells in culture. A maximal response of cyclic AMP content at 400% above control is observed between 2 and 30 min after addition of the peptide, whereas an 8-fold stimulation of cyclic AMP released into the incubation medium is measured between 10 and 180 min. A linear 7-fold increase of corticotropin release is observed for up to 3 hr. Preincubation from 18 hr with the potent glucocorticoid dexamethasone has no effect on C-RF-induced cyclic AMP accumulation. The same treatment with dexamethasone causes an 80% inhibition of corticotropin release induced by both C-RF and the cyclic AMP derivative 8-bromoadenosine 3',5'-cyclic monophosphate. The present data show that ovine C-RF is a potent stimulator of cyclic AMP accumulation in rat anterior pituitary cells and that the process is insensitive to the action of dexamethasone. The marked inhibition by dexamethasone of corticotropin secretion induced by a cyclic AMP derivative indicates that glucocorticoids exert their potent inhibitory effects on corticotropin secretion at a step distant to cyclic AMP formation.

Adrenocorticotropic Hormone↗
PubMed1982

Tumor growth inhibition in patients with prostatic carcinoma treated with luteinizing hormone-releasing hormone agonists.

Ten patients with prostatic carcinoma--six with stage C and four with stage D disease--were treated for 6 weeks to 12 months with agonistic analogues of luteinizing hormone-releasing hormone (LH-RH). [D-Trp6]LH-RH was given subcutaneously once daily at a dose of 100 microgram and [D-Ser(But)6]des-GlyNH2(10)-LH-RH ethylamide (HOE 766) was given subcutaneously (50 microgram once daily) or intranasally (500 microgram twice daily). In all patients, mean plasma testosterone levels showed a 75% suppression by the third week of treatment and remained low thereafter. This was followed by a decrease or normalization of plasma acid phosphatase levels by the second month of treatment and a 47% decrease in serum alkaline phosphatase by the 10th week of treatment in all but one patient. In patients with stage C disease presenting with prostatism or urinary outflow obstruction, there was a noticeable clinical improvement. In two such patients, a decrease in the size of the prostate was confirmed by ultrasonography. In patients with stage D disease manifested by diffuse bone metastases, there was relief of bone pain, and in one patient treated for greater than 12 months the improvement was documented by radioisotope bone imaging. It is concluded that superactive agonistic LH-RH analogues hold promise as therapeutic agents in patients with androgen-sensitive prostatic adenocarcinoma. Furthermore, the analogous of LH-RH may be used to assess the responsiveness of patients to surgical castration. Long-term administration of LH-RH analogues could become an alternative to surgical castration and estrogen therapy for the treatment of hormone-dependent prostatic carcinoma.

Buserelin↗
PubMed1982

Effects of chronic treatment with a potent luteinizing hormone releasing hormone agonist on serum luteinizing hormone and steroid levels in the male rhesus monkey.

The effects of chronic administration of [D-Ser(TBU)6, des-Gly-NH2 10]LHRH ethylamide (Buserelin, Hoe 766) on plasma LH, pregnenolone, 17-hydroxyprogesterone, testosterone and dihydrotestosterone levels were studied in a nonhuman primate species, the rhesus monkey. After 1 week of daily administration of 25 micrograms of Hoe 766, the LH response measured after 3 h and 7 h is markedly inhibited when compared to the previous week's response and a slight decrease in basal LH levels is observed. A small rise of plasma LH is, however, always seen 3 h after administration of the peptide during the whole treatment period. Serum testosterone levels display a rapid stimulation from 7 to 35 ng/ml 3 h after the first administration of Buserelin and increase progressively up to at least 12 h (44 ng/ml). Plasma concentrations of 17-hydroxyprogesterone increase more slowly from 2.0 to 3.4 ng/ml during the first 3 h and reach 9.5 ng/ml 9 h later. By contrast, there are no or minimal changes or serum pregnenolone and dihydrotestosterone levels following the first injection of Hoe 766 and during the course of the study. While the acute testosterone response to Buserelin measured at 3 h is not affected in up to seven weeks of treatment with the peptide, the duration of testosterone and 17-hydroxyprogesterone response measured at later time intervals (7 h, 12 h) is decreased to 20% to 50% of control. The data suggest that the testicular steroidogenic pathway in rhesus monkeys retain its ability to respond to LH stimulation during treatment with the LHRH agonist while the basal testosterone levels are reduced. The close correlation observed between reduced serum LH and testosterone concentrations suggest that pituitary desensitization is the main factor responsible for the partial inhibition of basal testosterone concentration in rhesus monkeys.

Animals↗
PubMed1982

[3H]Apomorphine binding to a GTP-sensitive dopaminergic site in bovine anterior pituitary gland.

The characteristics of binding of the potent dopaminergic agonist [3H]apomorphine have been studied in bovine anterior pituitary membranes. A high affinity binding site with an apparent dissociation constant (KD) of 0.7 nM and a number of binding sites of 56 fmol/mg protein has been measured when 10(-5) M dopamine was used to assess nonspecific binding. The order of potency of various agonists to compete with [3H]apomorphine binding is consistent with an interaction at a typical dopaminergic receptor: apomorphine greater than dopamine greater than (-)-epinephrine = (-)-norepinephrine much greater than (-)-isoproterenol. Competition for [3H]apomorphine binding by antagonists shows marked stereoselectivity, (+)-butaclamol being 4000 times more potent than (-)-butaclamol. Dihydroergocryptine, a potent dopaminergic agonist on prolactin release, as well as the dopaminergic antagonists spiroperidol, haloperidol, and (+)-butaclamol, compete for [3H]apomorphine binding at nanomolar concentrations. By contrast, adrenergic (phentolamine, propranolol, and clonidine) and serotonergic (serotonin, cyproheptadine, and methysergide) agonists and antagonists do not compete or are weak competitors at micromolar concentrations. Guanosine triphosphate (GTP) decreases [3H]apomorphine binding, the affinity of this ligand for the receptor being decreased 10 times by 300 microM GTP. The close correlation observed between the affinity of a series of agonists and antagonists for the [3H]apomorphine binding sites and their potency as modulators of prolactin release suggests that [3H]apomorphine binding sites are those involved in the control of prolactin secretion.

Animals↗
PubMed1982

Effects of estradiol on intact and denervated striatal dopamine receptors and on dopamine levels: a biochemical and behavioral study.

The present study describes the effect of chronic estrogen treatment on striatal dopamine levels and dopamine receptors, as well as on apomorphine-induced circling, a behavioral model reflecting dopaminergic activity in the rat striatum. Although estradiol itself does not show any affinity for the striatal dopamine receptor, its administration for 2 weeks in adult ovariectomized rats leads to a small increase in [3H]spiroperidol, [3H]haloperidol, and [3H]apomorphine binding in the striatum; this increase is associated with a greater number of binding sites. In order to dissociate possible pre- and post-synaptic effects of estrogens, these studies were next performed in animals bearing an unilateral 6-hydroxydopamine lesion of the substantia nigra. The apomorphine-induced circling behavior of rats bearing such a lesion was not affected by estrogen treatment. Estradiol treatment induced an increase of [3H]spiroperidol binding in both the intact and lesioned striatum, thus suggesting an estrogenic effect on a population of postsynaptic receptors. Chronic estradiol treatment reduced the concentration of dopamine in the striatum while the turnover of this amine measured using alpha-methyl-p-tyrosine remained unchanged. The present results show that estradiol exerts effects at the striatal level on both dopamine metabolism and receptor levels.

Animals↗
PubMed1982

Study of the direct action of luteinizing hormone-releasing hormone agonists at the testicular level in intact rats treated with an antiluteinizing hormone serum.

Is it well known that LHRH agonists can inhibit testicular functions by gonadal desensitization secondary to endogenous LH release and that a direct action at the gonadal level has also been demonstrated. Since an excess of anti-LH serum can be used, as an alternative to hypophysectomy, to neutralize the influence of endogenous LH release, the relative importance of the testis and pituitary gland in the inhibitory effect of a LHRH agonist, [D-Ser-(TBU)6,des-Gly-NH210]LHRH ethylamide (Buserelin), was studied on gonadal gonadotropin receptors in intact adult male rats treated with equine anti-LH or normal horse serum (NHS). A single administration of increasing doses (1-100 ng) of Buserelin leads to a progressive inhibition of testicular LH and PRL receptor levels by 70% and 40%, respectively, in animals injected with NHS. Treatment with the anti-LH serum completely prevents this inhibitory effect of a single dose of the LHRH agonist. After two successive injections of Buserelin in NHS-treated animals, testicular LH receptors are reduced by 70% and 80% with the 100- and 500-ng doses, respectively, while testicular PRL receptors are inhibited by 40-60%. In animals treated with the anti-LH serum, the inhibition of testicular LH receptors is reduced by only 18% (100 ng Buserelin) and 55% (500 ng Buserelin), while the inhibitory effect on PRL receptors is abolished. The present data show that endogenous LH release induced by a single injection of a LHRH agonist plays an essential role in the loss of testicular LH receptors measured 2 days later. Moreover, upon repeated injection of the LHRH agonist, neutralization of endogenous LH release by an anti-LH serum markedly reduces the inhibitory effect of the LHRH agonist on LH receptors, while it completely prevents the effect on PRL receptors, suggesting that the inhibitory effect of the LHRH agonist in the male rat is predominantly due to endogenous LH release rather than to a direct action of the peptide at the testicular level.

Animals↗
PubMed1982

Specific inhibition by glucocorticoids of the alpha 2-adrenergic stimulation of adrenocorticotropin release in rat anterior pituitary cells.

Previous studies have shown that a specific alpha 1-adrenergic receptor leads to a 7- to 12-fold stimulation of ACTH release in rat adenohypophyseal cells in culture. The ACTH response to epinephrine is inhibited by 65% after a 3-h incubation with the glucocorticoid agonist dexamethasone, whereas a complete suppression of the response is observed when the steroid is added 4 h earlier. Upon placing the inhibited cells in steroid-free medium, a 50% reversal of the inhibition of the ACTH response is observed after 10 h, whereas normal responsiveness is obtained after 36 h. Glucocorticoid agonists lead to a complete inhibition of epinephrine-induced ACTH secretion with the following order of potencies (ED50 values): triamcinolone acetonide (0.2 nM) much greater than dexamethasone (1.5 nM) much greater than cortisol (11 nM) greater than corticosterone (22 nM). Preincubation with dexamethasone for 4 h leads to an 85% decrease in the maximal ACTH response to epinephrine, whereas the ED50 value of catecholamine action is only slightly increased. Although the activity of the pituitary-adrenocortical axis is highly sex dependent in the rat, 17 beta-estradiol, 5 alpha-dihydrotestosterone, and the pure progestin R5020 have no detectable effect on either basal or epinephrine-induced ACTH release, thus suggesting that sex steroids exert their action in the intact animal at sites other than in corticotrophs. The finding of a specific inhibitory effect of glucocorticoids on epinephrine-induced ACTH secretion lends further support to the suggestion of a physiological role for the pituitary alpha 1-adrenergic receptor in the control of ACTH secretion (at least in the rat). The complete lack of effect of sex steroids indicates the high degree of specificity of the feedback mechanisms controlling ACTH secretion.

Adrenocorticotropic Hormone↗
PubMed1982

Direct effects of sex steroids on prolactin release at the anterior pituitary level: interactions with dopamine, thyrotropin-releasing hormone, and isobutylmethylxanthine.

When present alone for 4 or 8 days, 5 alpha-dihydrotestosterone (DHT) or the pure progestin R5020 (17,21-dimethyl-19-nor-4,9-pregnadiene-3,20-dione) inhibits spontaneous PRL release by 33--50% in rat anterior pituitary cells in primary culture. This inhibitory effect of DHT and R5020 can only be partially reversed by 17 beta-estradiol (E alpha). DHT and R5020 inhibit spontaneous PRL release in E2-primed cells at ED50 values of 0.5 and 3 nM, respectively. While E2 diminishes by 30--60% the maximal inhibitory effect of dopamine on PRL release and increases by 10-fold the ED50 value of dopamine action, DHT and R5020 can prevent by 30--60% the action of E2 and thus increase the potency of dopamine to inhibit PRL release. The inhibitory action of DHT and R5020 as well as the stimulatory action of E2 on spontaneous PRL release are similarly expressed on TRH- and 3-isobutyl-1-methylxanthine-induced PRL release, thus suggesting that at least part of the highly effective modulatory effects of sex steroids are exerted at a step after cAMP formation.

1-Methyl-3-isobutylxanthine↗