Repositório Institucional - Unifesp :: Navegando por Palavras-chave "prolactin"

Navegando por Palavras-chave "prolactin"

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Dopamine Transporter Regulation during Four Nights of REM Sleep Deprivation Followed by Recovery - An in vivo Molecular Imaging Study in Humans
(Amer Acad Sleep Medicine, 2010-02-01) Martins, R. C. S. [UNIFESP]; Andersen, Monica Levy [UNIFESP]; Garbuio, Silvério Aparecido [UNIFESP]; Bittencourt, Lia Rita Azeredo [UNIFESP]; Guindalini, Camila [UNIFESP]; Shih, M. C. [UNIFESP]; Hoexter, M. Q. [UNIFESP]; Bressan, Rodrigo Affonseca. A. [UNIFESP]; Castiglioni, M. L. V. [UNIFESP]; Tufik, Sergio [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
Objectives: To assess the influence of total or selective REM sleep deprivation on the dopamine transporter (DAT) densities and sleep patterns of healthy volunteers.Design: Prospective study.Setting: Evaluation of polysomnography recordings and DAT density after 4 nights of selective REM sleep deprivation followed by 3 nights of sleep recovery compared to a control group and a group that was subjected to 2 nights of total sleep deprivation. Single positron emission computed tomography and [(99m)Tc]TRODAT-1 were used to assess the cerebral DAT density in the striatum at baseline, after REM sleep deprivation and total sleep deprivation as well as after sleep recovery. Blood was collected daily to examine prolactin and estradiol levels, which were correlated with dopaminergic activity.Patients or Participants: Thirty healthy male volunteers ranging from 19 to 29 years of age were randomly assigned to one of three experimental groups after giving written informed consent (10 non-sleep deprived, 10 total sleep deprived, and 10 REM sleep deprived).Measurements and Results: Four nights of REM sleep deprivation and 2 nights of total sleep deprivation induced distinct and heterogeneous patterns of sleep recovery. No significant modulation of DAT availability was observed within groups. In the recovery nights, changes in cortisol, prolactin and estradiol concentrations were significantly correlated with specific sleep stages in the total and REM sleep deprived groups. In addition, DAT density was positively correlated with estradiol concentration and inversely associated with SWS latency only after total sleep deprivation.Conclusion: Our study demonstrates that although sleep deprivation did not promote significant alterations in DAT density within the striatum, there were significant correlations among transporter availability, hormonal concentrations and sleep parameters.
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Effects of metoclopramide-induced hyperprolactinemia on the prolactin receptor of murine endometrium
(Elsevier B.V., 2010-03-15) Rossi, Alexandre Guilherme Zabeu [UNIFESP]; Gomes, Regina Célia Teixeira [UNIFESP]; Simões, Manuel de Jesus [UNIFESP]; Simões, Ricardo dos Santos [UNIFESP]; Oliveira, Patricia B. [UNIFESP]; Soares, Jose Maria [UNIFESP]; Baracat, Edmund Chada [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP)
Objective: To evaluate the effects of metoclopramide-induced hyperprolactinemia, on the prolactin receptor of murine endometrium.Design: Experimental study using the RNA extraction to detect tissue prolactin recepter isoforms by reverse-transcriptase polymerase chain reaction (RT-PCR).Setting: University-based laboratory.Animal(s): Seventy-two female swiss albino mice (Mus musculus), approximately 100 days old, were divided into six 12-animal groups: (Cl) nonoophorectomized mice given vehicle; (GII) nonoophorectomized mice treated with metoclopramide; (Gill) oophorectomized mice treated with metoclopramide; (GIV)oophorectomized mice treated with metoclopramide and 17 beta-estradiol; (GV) oophorectomized mice treated with metoclopramide and micronized progesterone; (GVI) oophorectomized mice treated with metoclopramide and a solution of 17 beta-estradiol and micronized progesterone.Intervention(s): Drugs were administered for 50 days. Following euthanasia, the middle portions of the uterine horns were removed, sectioned, and immediately frozen for RT-PCR procedures. Blood was collected for the dosage of prolactin and serum estrogen and progesterone using radioimmune assay.Main Outcome Measure(s): Identification of uterine prolactin receptor isoforms:Result(s): the PRL receptor and its isoform L were identified only in GI (control group) and GII (metoclopramide), the two groups with nonoophorectomized animals. the amount of PRL receptor mRNA and that of its isoform L from GII were the largest. No other isoforms of the prolactin receptor were identified in any of the groups.Conclusion(s): Our results suggest that replacement of estrogen and progestin may not increase the mRNA of endometrial PRL receptor in metoclopromide-induced hyperprolactinemia in rats after castration. (Fertil Steril (R) 2010;93:1643-9. (C)2010 by American Society for Reproductive Medicine.)
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Endocrinological and catecholaminergic alterations during sleep deprivation and recovery in male rats
(Blackwell Publishing Ltd, 2005-03-01) Andersen, Monica Levy [UNIFESP]; Martins, Paulo José Forcina [UNIFESP]; D'Almeida, Vânia [UNIFESP]; Bignotto, Magda [UNIFESP]; Tufik, Sergio [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
Since previous data of our group showed increased concentrations in HPA axis hormones in sleep deprived rats, we hypothesized that this augmentation could produce effects in other hormonal systems, particularly in the sexual system. Considering that little is known about how the hormonal system changes during the recovery period after sleep deprivation (SD), our objective was to examine from what point SD alters sexual and stress-related hormones along with plasma catecholamine concentrations during 4 days. We also sought to verify the time course of their recovery after an equivalent period of recovery sleep. Rats were deprived of sleep by the platform technique for 1-4 days and were allowed to recover for the same period. Plasma catecholamines [dopamine (DA) and noradrenaline (NOR)], testosterone, estrone, progesterone, prolactin, corticosterone and adrenocorticotropic hormone (ACTH) concentrations were measured. Comparisons between groups showed that the SD procedure used in the present study produced marked alterations in almost all studied hormones from 24 h of SD, except for estrone and prolactin (which required 96 h of SD to become altered). Testosterone and estrone decreased, whereas progesterone, prolactin, corticosterone, ACTH, DA and NOR increased. During recovery period, progesterone, prolactin and corticosterone concentrations returned to control levels, whereas testosterone, estrone, NOR and DA did not. in addition, after 48 h of recovery ACTH and NOR decreased below control concentrations, remaining low until 96 h of sleep recovery. Thus, SD showed long lasting, differential effects upon these neurochemicals suggesting that each has its own pattern of responses to SD as well as variable periods of recovery.
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Endovascular treatment of intracavernous carotid aneurysm with hyperprolactinaemia
(Edizioni Centauro, 1998-09-01) Caldas, Jose Guilherme Mendes Pereira [UNIFESP]; Cavalheiro, Sergio [UNIFESP]; Nalli, Darcio Roberto [UNIFESP]; Frudit, Michel Eli [UNIFESP]; Puglia, P.; Universidade de São Paulo (USP); Universidade Federal de São Paulo (UNIFESP); Hosp NS Lourdes
A 42-year-old woman presented with headache, galactorrhoea, marked hyperprolactinemia and normal neurologic examination.CT MR and MR-angiography showed an intracavernous carotid artery aneurysm with minimal displacement of the pituitary stalk. Treatment by embolisation using GDC coils allowed exclusion of the aneurysm.Galactorrhoea resolved and serum prolactin levels fell to normal after eight months. Followup MR showed absence of the aneurysm, although the discrete mass effect persisted, suggesting that hyperprolactinaemia was due to pulsatility.
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Hormonal profile, the PROGINS polymorphism, and erectile dysfunction complaints: data from a population-based survey
(Elsevier B.V., 2011-02-01) Andersen, Monica L. [UNIFESP]; Alvarenga, Tathiana A. [UNIFESP]; Mazzotti, Diego R. [UNIFESP]; Guindalini, Camila [UNIFESP]; Pellegrino, Renata [UNIFESP]; Barrueco, Karina F. [UNIFESP]; Santos-Silva, Rogerio [UNIFESP]; Bittencourt, Lia R. [UNIFESP]; Tufik, Sergio [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
Objective: To evaluate a potential association among the hormonal profile, PROGINS polymorphism, and erectile dysfunction (ED) complaints in a large population-based sample in São Paulo, Brazil.Design: Population-based questionnaire study.Setting: Interviews, sleep recording, and blood sample were conducted in a sleep institute.Patient(s): the total study participants included 467 men.Intervention(s): General information was obtained through interviews, and a blood sample was collected for hormone levels, DNA extraction, and PROGINS genotyping.Main Outcome Measure(s): the effect of progesterone and the PROGINS polymorphism on the risk of developing ED were measured by questionnaire and blood sample.Result(s): Progesterone, prolactin, testosterone, and estradiol levels did not differ between the genotype groups (T1/T1 and T1/T2+T2/T2). No significant genotypic or allelic differences were found between individuals with ED complaints and controls. Multivariate logistic regression analyses including age, body mass index, hypertension, diabetes, apnea-hypopnea index, and genetic ancestry estimation, as well as the PROGINS polymorphism, confirmed the lack of association between the T2 allele carriers and the risk of ED(odds ratio = 0.80; 95% confidence interval = 0.40-1.62).Conclusion(s): This is the first study to demonstrate the genotypic and allelic frequencies of the PROGINS polymorphism in a large population-based sample of men. the results do not support a direct role for the PROGINS polymorphism in the risk of developing ED; however, further examination of other variants within PR gene will be necessary to completely rule out an effect. (Fertil Steril (R) 2011;95:621-4. (C) 2011 by American Society for Reproductive Medicine.)
Acesso aberto (Open Access)
Hormone profile in acute psychotic disorders: A cross-sectional comparison of serum hormone concentrations in treated and untreated male patients with schizophrenia
(Elsevier B.V., 2006-09-01) Costa, Anna Maria Niccolai [UNIFESP]; Lima, Mauricio Silva de [UNIFESP]; Tosta, Juliana; Rodrigues Filho, Salomao; Oliveira, Irismar Reis de; Sena, Eduardo Pone de; Mari, Jair de Jesus [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Bristol Myers Squibb Co; Fed Univ Pelotas; Eli Lilly Brazil; Pax Clin Psiquiatrica; Universidade Federal da Bahia (UFBA)
Background: Antipsychotic drugs for the treatment of schizophrenia provide effective treatment of psychotic symptoms but might lead to neuroendocrine abnormalities.Objective: the aim of this study was to assess hypothalamic-pituitary-gonadal (HPG) axis function by comparing serum hormone profiles of newly admitted patients with psychotic disorders who were receiving antipsychotic drugs with those who were antipsychotic-drug-free during the preceding 6 months.Methods: Adult male patients admitted during a 1-year period (December 1999 to December 2000) to I of 2 Brazilian public psychiatric inpatient units that provide care for severely ill patients were eligible for this cross-sectional study if they had a diagnosis of schizophrenia based on the criteria given in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and a score > 24 on the Brief Psychiatric Rating Scale. On the morning after admission, serum concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), sex hormone-binding globulin (SHBG), prolactin, free testosterone (FT), and total testosterone (TT) were determined. A commercial laboratory provided the normal serum hormone concentrations of healthy Brazilian men in the same age range as that of the study patients.Results: Sixty-three adult male patients, aged 18 to 55, were included in the study. Forty-eight (76.2%) patients (mean [SD] age, 30.6 [8.9] years) were receiving antipsychotic drugs (treated). Fifteen (23.8%) patients (mean [SD] age, 36.5 [9.8] years) were antipsychotic-drug-free for 6 months before admission (untreated). the only significant between-group difference was for disease duration (treated, 7.6 [8.1] years vs untreated, 12.3 [9.7] years; P = 0.044). Treated patients were more likely to have higher dispersed serum hormone concentrations than the untreated patients. Serum concentration of FSH was numerically higher in the treated patients than in the untreated patients, although the difference was not statistically significant. Compared with the control group (1436 men and women for prolactin; 226 men for LH; 207 for FSH; 128 for TT; 128 for FT; and 128 for SHBG), patients in the treated group had significantly different mean [SD] serum concentrations of all hormones (treated vs control: prolactin, 24.3 [23.7] mu g/L vs 6.8 [0.12] mu g/L, P < 0.001; LH, 4.9 [3.4] U/L vs 3.3 [0.13] U/L, P = 0.001; FSH, 4.4 [3.9] U/L vs 3.0 [0.06] U/L, P = 0.025; TT, 17.5 [7.8] nmol/L vs 20.1 [1.64] nmol/L, P = 0.004; FT, 0.056 [0.08] nmol/L vs 0.06 [0.003] nmol/L, P < 0.001; and SHBG, 33.3 [18.9] nmol/L vs 48.4 [1.45] nmol/L, P = 0.002). Compared with the control group, patients in the untreated group had significantly different mean (SD) serum concentrations of all hormones except FSH and TT (untreated vs control: prolactin, 19.9 [12.8] mu g/L vs 6.8 [0.12] mu g/L, P = 0.001; LH, 6.0 [1.9] U/L vs 3.3 [0.13] U/L, P = 0.002; FT, 0.08 [0.04] nmol/L vs 0.06 [0.003] nmol/L, P = 0.001; and SHBG, 26.6 [11.6] nmol/L vs 48.4 [1.45] nmol/L, P < 0.001). No differences were found between the TT distribution curve of the control group and that of the untreated patients.Conclusion: This study supports further investigation of a potential difference in the HPG axis among treated and untreated patients with schizophrenia and those who do not have that condition.
Acesso aberto (Open Access)
Hypopituitarism and amenorrhea- galactorrhea syndrome caused by thrombosis of both internal carotid artery and giant intrasellar aneurysm: case report
(Academia Brasileira de Neurologia - ABNEURO, 2004-03-01) Gondim, Jackson; Schops, Michele [UNIFESP]; Ferreira, Erica; Fortaleza General Hospital Department of Neuroendocrinology; Universidade Federal de São Paulo (UNIFESP); Federal University of Ceará Department of Anesthesiology; Fortaleza General Hospital Department of Neck and Head Surgery
Giant intra and parasellar aneurysm with a spontaneous thrombosis of internal carotid artery is rare. We report the case of a 34 years old woman presenting a unique giant sellar and parasellar aneurysm associated with hypopituitarism and amenorrhea-galactorrhea syndrome. Computed tomographic scans and magnetic resonance images were suggestive of a sellar tumor with a cystic component. Digital cerebral angiography showed spontaneous thrombosis of a intrasellar and parasellar carotid artery aneurysm and left internal carotid artery in the neck. A transseptal endoscopic biopsy was done and confirmed a thrombosed aneurysm. No other surgical treatment was required in this patient but permanent endocrinological treatment was necessary.
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Hypoprolactinemic rats under conditions of constant darkness or constant light. Effects on the sleep-wake cycle, cerebral temperature and sulfatoxymelatonin levels
(Elsevier B.V., 1999-07-24) Lobo, L. L.; Claustrat, B.; Debilly, G.; Paut-Pagano, L.; Jouvet, M.; Valatx, J. L.; Univ Lyon 1; Ctr Med Nucl; Universidade Federal de São Paulo (UNIFESP)
In genetic hypoprolactinemic rats under light-dark (LD) conditions, the circadian rhythms of slow-wave (SWS) and paradoxical (PS) sleep display an alteration of their phase relationship. the aim of our study was to investigate the effects of constant darkness (DD) or constant light (LL) on the daily distribution and amounts of sleep-wake stages, cerebral temperature and concentrations of the urinary melatonin metabolite, 6-sulfatoxymelatonin, in prolactin-deficient rats. After 3 weeks of DD, the SWS period was 24 h 8 +/- 6 min and the acrophase occurred at 15:44 +/- 1.35, while for PS, the period was more stable than during LD (24 h 10 +/- 8 min vs. 24 h 55 +/- 43 min) and the acrophase occurred at 16:44 +/- 1:54. Under LL conditions, circadian sleep rhythms persisted during the first 3 days, then completely disappeared during the third week, to be replaced by ultradian rhythms (period of 4-6 h). Time-series analysis showed that the two sleep states became synchronous as early as the second day under constant conditions; the total amount of PS was increased under both conditions (LL and DD) at the expense of duration of waking. Under LD and constant conditions, the pattern of changes in cerebral temperature was similar to that for wakefulness (W). Sulfatoxymelatonin was rhythmically secreted under both LD and DD conditions, whereas, under LL conditions, its rhythm was abolished. the results show that, in IPL rats in the absence of a zeitgeber, the PS and SWS rhythms recover a synchronous phase relationship and PS amounts are increased. (C) 1999 Elsevier Science B.V. All rights reserved.
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Hypothalamic involvement in chronic migraine
(British Med Journal Publ Group, 2001-12-01) Peres, Mario Fernando Prieto [UNIFESP]; del Rio, M. S.; Seabra, MLV; Tufik, Sergio [UNIFESP]; Abucham, Julio [UNIFESP]; Cipolla-Neto, J.; Silberstein, S. D.; Zukerman, Eliova [UNIFESP]; São Paulo Headache Ctr; Thomas Jefferson Univ Hosp; Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP)
Objectives-Chronic migraine (CM), previously called transformed migraine, is a frequent headache disorder that affects 2%-3% of the general population. Analgesic overuse, insomnia, depression, and anxiety are disorders that are often comorbid with CM. Hypothalamic dysfunction has been implicated in its pathogenesis, but it has never been studied in patients with CM. the aim was to analyze hypothalamic involvement in CM by measurement of melatonin, prolactin, growth hormone, and cortisol nocturnal secretion.Methods-A total of 338 blood samples (13/patient) from 17 patients with CM and nine age and sex matched healthy volunteers were taken. Melatonin, prolactin, growth hormone, and cortisol concentrations were determined every hour for 12 hours. the presence of comorbid disorders was also evaluated.Results-An abnormal pattern of hypothalamic hormonal secretion was found in CM. This included: (1) a decreased nocturnal prolactin peak, (2) increased cortisol concentrations, (3) a delayed nocturnal melatonin peak in patients with CM, and (4) lower melatonin concentrations in patients with CM with insomnia. Growth hormone secretion did not differ from controls.Conclusion-These results support hypothalamic involvement in CM, shown by a chronobiologic dysregulation, and a possible hyperdopaminergic state in patients with CM. Insomnia might be an important variable in the study findings.
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Moclobemide effects on prolactin plasma levels in healthy individuals: the hormonal increase induced by a single dose is maintained during a 4-week period of drug intake
(Lippincott Williams & Wilkins, 1997-11-01) Juruena, M. F.; Pires, MLN; Calil, H. M.; Universidade Federal de São Paulo (UNIFESP)
Neuroendocrine challenge studies are frequently used to study the pathophysiology of psychiatric illnesses and the effects of psychotropic drug treatment on brain monoamine function. Moclobemide, a reversible inhibitor of monoamine oxidase, with predominant effects on the A-type of the enzyme, was administered to 15 healthy men. Seven out of the 15 also received single blind placebo a week before the moclobemide. the individuals received moclobemide as a single dose (150 mg), followed by doses of 150 mg three times a day, during a 4-week period. Plasma prolactin was measured in the morning over a 150-min period, following the single dose, and then at the end of weeks 1, 2 and 4 of moclobemide intake. the present data show an acute and transitory increase of plasma prolactin levels after the single dose, and also during the long-term moclobemide administration. It might indicate that steady-state moclobemide levels, during the long-term drug administration, were low and thus large fluctuations of drug levels occurred between doses. Thus, it is suggested that larger doses or administering smaller doses more frequently, or both, may induce hyperprolactinaemia with clinical consequences.
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A naturalistic, 9-month follow-up, comparing olanzapine and conventional antipsychotics on sexual function and hormonal profile for mates with schizophrenia
(Sage Publications Ltd, 2007-03-01) Nicolai Costa, Anna Maria; Lima, Mauricio Silva de; Faria, Marite; Rodrigues Filho, Salomao; Olivrira, Irismar Reis de; Mari, Jair de Jesus; Universidade Federal de São Paulo (UNIFESP); Univ Fed Pelotas; Univ Catolica Pelotas; Pax Clin Psiquiat; Universidade Federal da Bahia (UFBA)
Second generation antipsychotics have less influence on prolactin levels than conventional antipsychotics (CA), which are commonly associated with sexual dysfunction and hyperprolactinaemia. However, only a few studies have been conducted assessing these newer antipsychotics and sexual function/dysfunction. the aim of this study is to evaluate the sexual function and hormonal profile of mate schizophrenic patients taking olanzapine or CA. Sixty-three inpatients with acute episodes of schizophrenia were randomly assigned to take either olanzapme, or go on conventional antipsychatic treatment. the Dickson-GLazer sexual functioning questionnaire was used to assess sexual functioning where serum protactin, luteinizing hormone, follicle-stimulating hormone, total testosterone, free testosterome, and sex hormone-binding globulin concentrations were measured. All measurements were taken on discharge from the inpatient unit (baseline), and again at 3 and 9 months after discharge. Prolactin levels in the olanzapine group decreased more rapidly and were significantly lower than in the CA group after 3 months (12.1 +/- 6.3 mu g/l, p=0.01; 18.1 +/- 11.2 mu g/l, p=0.564, respectively). After nine months, there was a tendency toward normal levels in both groups, and the frequency of sexual complaints did not differ between the groups. This study showed no difference between olanzapine and conventional antipsychotics regarding sexual complaints in the treatment of schizophrenia, but did show a difference in the hormone teveL normalization rate.
Acesso aberto (Open Access)
Neuroendocrine and Peptidergic Regulation of Stress-Induced REM Sleep Rebound
(Frontiers Media Sa, 2016) Machado, Ricardo Borges [UNIFESP]; Suchecki, Deborah [UNIFESP]
Sleep homeostasis depends on the length and quality (occurrence of stressful events, for instance) of the preceding waking time. Forced wakefulness (sleep deprivation or sleep restriction) is one of the main tools used for the understanding of mechanisms that play a role in homeostatic processes involved in sleep regulation and their interrelations. Interestingly, forced wakefulness for periods longer than 24 h activates stress response systems, whereas stressful events impact on sleep pattern. Hypothalamic peptides (corticotropin-releasing hormone, prolactin, and the CLIP/ACTH (18-39)) play an important role in the expression of stress-induced sleep effects, essentially by modulating rapid eye movement sleep, which has been claimed to affect the organism resilience to the deleterious effects of stress. Some of the mechanisms involved in the generation and regulation of sleep and the main peptides/hypothalamic hormones involved in these responses will be discussed in this review.
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Neuroendocrine effects of quetiapine in healthy volunteers
(Cambridge Univ Press, 2005-03-01) Guerra, Alexandro de Borja Gonçalves [UNIFESP]; Castel, Saulo [UNIFESP]; Benedito-Silva, Ana Amélia [UNIFESP]; Calil, Helena Maria [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
The present study measured prolactin, cortisol, ACTH and growth hormone in healthy male volunteers following an acute oral administration of quetiapine, an atypical antipsychotic with high affinity for H, and moderate affinity for sigma, sigma(1), 5-HT2, alpha(2) and D-2 receptors. Fifteen male volunteers entered this randomized double-blind, cross-over, placebo-controlled study. Blood samples were drawn every 30 min from 09:00 hours to 13:00 hours. the first samples were drawn immediately before the administration of 150 mg quetiapine or placebo. Mean results for each hormone and ANOVA for repeated measures were performed. the area under the curve (AUC) hormonal values were calculated and compared by paired t test. the ANOVA showed an increase of prolactin after quetiapine administration from time 60 min up to the end of the observation period. Cortisol decreased after quetiapine administration from time 150 min to time 240 min. ACTH secretion showed no difference compared to placebo. There was a late increase in growth hormone secretion, significant in comparison with placebo only at time 210 min. the AUC values were statistically different for prolactin and cortisol compared to placebo. A single dose of quetiapine (150 mg) increased prolactin secretion probably due to a transiently high D, receptor occupancy at the anterior pituitary. Cortisol secretion decreased as was expected from quetiapine's pharmacodynamic profile. the lack of response of ACTH might be, at least in part, explained by the low hormonal assay sensitivity. the late growth hormone increase might have been due to quetiapine's antagonism of H, receptors.
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Prolactinemia is uncoupled from central D-2/D-3 dopamine receptor occupancy in amisulpride treated patients
(Springer, 2004-09-01) Bressan, R. A.; Erlandsson, K.; Spencer, E. P.; Ell, P. J.; Pilowsky, L. S.; Universidade Federal de São Paulo (UNIFESP); Univ London Kings Coll; UCL Med Sch; Guys & St Thomas Hosp Trust
Atypical antipsychotic drugs are classically associated with lower propensity to extrapyramidal symptoms (EPS) and hyperprolactinemia than typical antipsychotic drugs. It has not been clarified why some atypical antipsychotic drugs, such as amisulpride, induce prolactin plasma concentration (PRL) elevation, but little EPS. Previous studies have found an association between striatal D-2/D-3 receptor occupancy and PRL in typical antipsychotic treated patients suggesting that PRL is a marker of central D-2/D-3 receptors blockade. Objective: We have evaluated the relationship between PRL and central (striatum, temporal cortex and thalamus) D-2/D-3 receptor occupancy in amisulpride treated schizophrenic patients. Methods: Single photon emission tomography (SPET) and [I-123]-epidepride were used to determine D-2/D-3 receptor occupancy in eight amisulpride treated patients. PRL was measured concurrently with the scans. Results: the mean PRL was 1166 (range 499-1892 mIU/1) for a mean amisulpride dose of 406 mg/day (range 150-600 mg/day). Amisulpride plasma concentration and central D-2/D-3 receptor occupancy were positively correlated (r=0.83-0.89, df=4, P<0.05). No significant correlations were observed between PRL and amisulpride (daily dose or plasma concentration, P>0.05), or between PRL and central D-2/D-3 receptor occupancy (P>0.05). Conclusions: Our findings show that amisulpride-induced hyperprolactinemia is uncoupled from central D-2/D-3 receptor occupancy. Amisulpride has poor blood-brain barrier penetration and reaches much higher concentration at the pituitary, which is outside the blood-brain barrier. Higher D-2/D-3 receptor occupancy at the pituitary gland than at central regions is a possible explanation for amisulpride PRL elevation with low EPS. Further studies evaluating pituitary D-2/D-3 receptor occupancy in vivo are necessary to confirm this hypothesis.
Acesso aberto (Open Access)
Protective Effect of Prolactin against Methylmercury-Induced Mutagenicity and Cytotoxicity on Human Lymphocytes
(Mdpi Ag, 2014-09-01) Silva-Pereira, Liz Carmem; Machado da Rocha, Carlos Alberto; Campos da Silva e Cunha, Luiz Raimundo; Costa, Edmar Tavares da; Araujo Guimaraes, Ana Paula; Pontes, Thais Brilhante; Wanderley Picanco Diniz, Domingos Luiz; Leal, Mariana Ferreira [UNIFESP]; Moreira-Nunes, Caroline Aquino; Burbano, Rommel Rodriguez; IFPA Itaituba; Fed Univ Para; IFPA; Univ Para; Fed Univ Western Para; Universidade Federal de São Paulo (UNIFESP)
Mercury exhibits cytotoxic and mutagenic properties as a result of its effect on tubulin. This toxicity mechanism is related to the production of free radicals that can cause DNA damage. Methylmercury (MeHg) is one of the most toxic of the mercury compounds. It accumulates in the aquatic food chain, eventually reaching the human diet. Several studies have demonstrated that prolactin (PRL) may be differently affected by inorganic and organic mercury based on interference with various neurotransmitters involved in the regulation of PRL secretion. This study evaluated the cytoprotective effect of PRL on human lymphocytes exposed to MeHg in vitro, including observation of the kinetics of HL-60 cells (an acute myeloid leukemia lineage) treated with MeHg and PRL at different concentrations, with both treatments with the individual compounds and combined treatments. All treatments with MeHg produced a significant increase in the frequency of chromatid gaps, however, no significant difference was observed in the chromosomal breaks with any treatment. A dose-dependent increase in the mitotic index was observed for treatments with PRL, which also acts as a co-mitogenic factor, regulating proliferation by modulating the expression of genes that are essential for cell cycle progression and cytoskeleton organization. These properties contribute to the protective action of PRL against the cytotoxic and mutagenic effects of MeHg.

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