Relationship of serum prolactin with severity of drug use and treatment outcome in cocaine dependence.

RATIONALE: Alteration in serum prolactin (PRL) levels may reflect changes in central dopamine activity, which modulates the behavioral effects of cocaine. Therefore, serum PRL may have a potential role as a biological marker of drug severity and treatment outcome in cocaine dependence. OBJECTIVE: We investigated whether serum PRL levels differed between cocaine-dependent (CD) subjects and controls, and whether PRL levels were associated with severity of drug use and treatment outcome in CD subjects. METHODS: Basal PRL concentrations were assayed in 141 African-American (AA) CD patients attending an outpatient treatment program and 60 AA controls. Severity of drug use was assessed using the Addiction Severity Index (ASI). Measures of abstinence and retention during 12 weeks of treatment and at 6-month follow-up were employed as outcome variables. RESULTS: The basal PRL (ng/ml) in CD patients (9.28+/-4.13) was significantly higher than controls (7.33+/-2.94) (t=3.77, P\u3c0.01). At baseline, PRL was positively correlated with ASI-drug (r=0.38, P\u3c0.01), ASI-alcohol (r=0.19, P\u3c0.05), and ASI-psychological (r=0.25, P\u3c0.01) composite scores, and with the quantity of cocaine use (r=0.18, P\u3c0.05). However, PRL levels were not significantly associated with number of negative urine screens, days in treatment, number of sessions attended, dropout rate or changes in ASI scores during treatment and at follow-up. Also, basal PRL did not significantly contribute toward the variance in predicting any of the outcome measures. CONCLUSION: Although cocaine use seems to influence PRL levels, it does not appear that PRL is a predictor of treatment outcome in cocaine dependence

Relationship between prolactin plasma levels and white matter volume in women with multiple sclerosis

BACKGROUND: The role of prolactin (PRL) on tissue injury and repair mechanisms in multiple sclerosis (MS) remains unclear. The aim of this work was to investigate the relationship between PRL plasma levels and brain damage as measured by magnetic resonance imaging (MRI). METHODS: We employed a chemiluminescence immunoassay for measuring plasma levels of PRL. We used a 1.5 T scanner to acquire images and Jim 4.0 and SIENAX software to analyse them. RESULTS: We included 106 women with relapsing remitting (RR) MS and stable disease in the last two months. There was no difference in PRL plasma levels between patients with and without gadolinium enhancement on MRI. PRL plasma levels correlated with white matter volume (WMV) (rho = 0.284, p = 0.014) but not with grey matter volume (GMV). Moreover, PRL levels predicted changes in WMV (Beta: 984, p = 0.034). CONCLUSIONS: Our data of a positive association between PRL serum levels and WMV support the role of PRL in promoting myelin repair as documented in animal models of demyelination. The lack of an increase of PRL in the presence of gadolinium enhancement, contrasts with the view considering this hormone as an immune-stimulating and detrimental factor in the inflammatory process associated with MS

The value of PRL in predicting prolactinοma in hyperprolactinemic PCOS

Background To identify a serum prolactin (PRL) cut‐off value indicative of a PRL‐producing adenoma in women with Polycystic Ovarian Syndrome (PCOS) and hyperprolactinemia and characterize such patients. Materials and methods In the present retrospective case‐control study the medical records of 528 PCOS women were reviewed. Pituitary magnetic resonance imaging (MRI) was performed in PCOS patients with PRL levels ≥94.0 ng/mL and/or symptoms suspicious of a pituitary adenoma (PA). Prolactinoma diagnosis was made in the presence of an MRI‐identifiable PA with biochemical and radiological response to dopamine agonists. Receiver operating characteristic (ROC) curve analysis was performed to determine a serum PRL threshold that could identify hyperprolactinemic PCOS subjects with prolactinomas. Clinical, metabolic and endocrine parameters were also analysed. Results Among 528 patients with PCOS, 60 (11.4%) had elevated PRL levels. Of 44 (73.3%) patients who had pituitary imaging, 19 had PAs, 18 normal MRI and 7 other abnormalities. Patients harboring prolactinomas had significantly higher PRL levels compared to patients without adenomas (median PRL 95.4 vs. 49.2 ng/mL, p<0.0001). A PRL threshold of 85.2 ng/mL could distinguish patients with prolactinomas with 77% sensitivity and 100% specificity [Area Under the curve (AUC) (95%) 0.91(0.8‐1.018), p=0.0001]. PCOS women with prolactinomas were younger and had lower LH levels compared to women without prolactinomas. Conclusions In women with PCOS, PRL levels exceeding 85.2 ng/mL are highly suggestive of a prolactinoma warranting pituitary imaging. Pituitary MRI could also be considered in young PCOS patients with milder PRL elevation and low LH levels

Prolactin

During an oral glucose tolerance test (OGTT) glucose and insulin levels were measured in 26 patients with prolactin-producing pituitary tumours without growth hormone excess. Basal glucose and insulin levels did not differ from the values of an age-matched control group. After glucose load the hyperprolactinaemic patients showed a decrease in glucose tolerance and a hyperinsulinaemia. Bromocriptine (CB 154), which suppressed PRL, improved glucose tolerance and decreased insulin towards normal in a second OGTT. — Human PRL or CB 154 had no significant influence on insulin release due to glucose in the perfused rat pancreas. — These findings suggest a diabetogenic effect of PRL. CB 154 might be a useful drug in improving glucose utilization in hormone-active pituitary tumours

Mirtazapine decreases stimulatory effects of reboxetine on cortisol, adrenocorticotropin and prolactin secretion in healthy male subjects

Reboxetine is a selective noradrenaline reuptake inhibitor, whereas mirtazapine acts as an antagonist at noradrenergic alpha(2), serotonin (5-HT2), 5-HT3 and histamine H-1 receptors. In a former study we could demonstrate an inhibitory impact of mirtazapine on cortisol secretion. In the present investigation, the influence of combined administration of 15 mg mirtazapine and 4 mg reboxetine on the cortisol ( COR), adrenocorticotropin ( ACTH), growth hormone (GH), and prolactin (PRL) secretion was examined in 12 healthy male subjects, compared to reboxetine alone ( 4 mg). In a randomized order, the subjects received reboxetine ( 4 mg) alone or the combination of reboxetine ( 4 mg) and mirtazapine ( 15 mg) at 8: 00 a. m. on two different days. After insertion of an intravenous catheter, blood samples were drawn 1 h prior to the administration of single reboxetine or the combination ( reboxetine and mirtazapine), at time of administration, and during the time of 5 h thereafter in periods of 30 min. Serum concentrations of COR, GH, and PRL as well as plasma levels of ACTH were determined in each blood sample by means of double antibody RIA, fluoroimmunoassay and chemiluminescence immunometric assay methods. The area under the curve (AUC) was used as parameter for the COR, ACTH, GH, and PRL response. For statistical evaluation, the Wilcoxon signed-ranks test was performed. There was a pronounced stimulation of COR, ACTH, GH, and PRL concentrations after single administration of reboxetine. When reboxetine was given in combination with mirtazapine, a significant reduction of the COR, ACTH, and PRL stimulation was observed whereas GH secretion patterns remained unchanged, compared to single administration of reboxetine. Apparently, the stimulatory effects of reboxetine on pituitary hormone secretion via noradrenergic mechanisms are counteracted in part by the alpha(2)-blocking properties of mirtazapine and its inhibitory influence on cortisol secretion. Copyright (C) 2004 S. Karger AG, Basel

The in vitro and in vivo effects of human growth hormone administration on tumor growth of rats bearing a transplantable rat pituitary tumor (7315b)

Abstract The direct effects of human GH and IGF-I on PRL secretion and cell proliferation were studied on PRL secreting rat pituitary tumor 7315b cells in vitro, as well as the effects in vivo of human GH administration on body weight, IGF-I levels and tumor size in rats bearing this transplantable tumor. In the in vitro studies IGF-I levels above 5 nM stimulated PRL release in a dose-dependent manner while GH, in concentrations of 0.23–45 nM, did not affect PRL release. Cell proliferation was stimulated by IGF-I in a dose-dependent manner from 0.5 nM onwards, while GH did not have an effect. The in vivo studies showed that 1 mg GH/rat/day prevented tumor-induced cachexia and normalized the suppressed IGF-I levels without stimulating tumor growth. It is concluded that tumor-induced cachexia can be prevented by exogenous GH administration without an increase in tumor mass, even if a tumor model is used whose cultured tumor cells respond to exposure to IGF-I with a mitotic response

Effects of antipsychotics on bone mineral density and prolactin levels in patients with schizophrenia: a 12-month prospective study

Objective: Effects of conventional and atypical antipsychotics on bone mineral density (BMD) and serum prolactin levels (PRL) were examined in patients with schizophrenia.Methods: One hundred and sixty-three first-episode inpatients with schizophrenia were recruited, to whom one of three conventional antipsychotics (perphenazine, sulpiride, and chlorpromazine) or one of three atypical antipsychotics (clozapine, quetiapine, and aripiprazole)was prescribed for 12 months as appropriate. BMD and PRL were tested before and after treatment. Same measures were conducted in 90 matched healthy controls.Results Baseline BMD of postero-anterior L1–L4 range from 1.04 ± 0.17 to 1.42 ± 1.23, and there was no significant difference between the patients group and healthy control group. However, post-treatment BMD values in patients (ranging from 1.02 ± 0.15 to 1.23 ± 0.10) were significantly lower than that in healthy controls (ranging from 1.15 ± 0.12 to 1.42 ± 1.36). The BMD values after conventional antipsychotics were significantly lower than that after atypical antipsychotics. The PRL level after conventional antipsychotics (53.05 ± 30.25 ng/ml) was significantly higher than that after atypical antipsychotics (32.81 ± 17.42 ng/ml). Conditioned relevance analysis revealed significant negative correlations between the PRL level and the BMD values after conventional antipsychotics.Conclusion The increase of PRL might be an important risk factor leading to a high prevalence of osteoporosis in patients with schizophrenia on long-term conventional antipsychotic medication.<br/

Prolactin responses to stress induced by a competitive swimming effort

Purpose:The aim of the present study was to investigate the changes in prolactin (PRL) plasma concentrations induced by competitive swimming practice. Methods:Twenty-three males, 13 trained swimmers (experimental group) and 10 sedentary and healthy students (age-matched control group) took part in this investigation. The swimmers were assessed at three points: basal conditions, pre-and post-swimming competition (100 m freestyle), whereas subjects from the control group only undertook the basal trial. The variables analysed were: several body composition measures, anxiety level (STAI questionnaire), PRL and lactic acid concentrations. Results:No statistical differences were observed in PRL basal levels between groups. An evident PRL response to pre-competition psychological stress was observed in the experimental group, since the PRL plasma concentration rosefrom 4.02±0.53 ng/ml (basal conditions) to 5.52±0.53 ng/ml (p≤0.05). The PRL response to the competitive effort produced an important increase in its plasma concentration (10.07±1.59 ng/ml), showed statistical differences from pre-competition (p≤0.01) and from basal conditions (p≤0.001). A significant rise in plasma lactate levels just at the end of the effort was found, although it did not correlate with PRL levels in the same situation. Conclusion:While we observed a remarkable response of PRL to psychological and physiological stress induced by a short term competitive effort in swimming, no changes in PRL basal levels were exhibitedwith swim training. More research is needed to clarify these findings

Thyroxine-binding globulin: investigation of microheterogeneity

Preparations of T4-binding globulin (TBG) from human serum was performed using only two affinity chromatography steps. Purity of the protein was demonstrated by a single band in overloaded disc and sodium dodecyl sulfate electrophoresis, equimolar binding to T4, and linearity in sedimentation velocity run. The molecular weight was calculated to be 60,000 +/- 3,000 daltons (n = 3), the sedimentation coefficient was 3.95S, and the Stokes' radius was 37 A. The amino acid composition was found to be in good agreement with the calculations of other authors. By isoelectric focussing (IEF), pure TBG showed four main bands at pH 4.25, 4.35, 4.45, and 4.55 together with several fainter bands. The N- acetylneuraminic acid (NANA) content of the four TBG bands isolated by preparative IEF was found to decrease from 10.2 mol NANA/mol TBG in the band at pH 4.25 to 4.8 mol NANA/mol TBG in the band at pH 4.55. No significant difference in the affinity constants of the TBG bands to T4 was found. The affinity constants for TBG ranged from 3.1 x 10(9) to 7.2 x 10(9) M-1. Sequential kinetic desialylation of pure TBG resulted in a progressive tendency toward one major band at pH 6.0. In native sera, microheterogeneity of TBG was detected after IEF on polyacrylamide gel plates by immunofixation. The typical TBG patterns shown by pure TBG were also found in normal subjects. Characteristic deviations from this pattern were found in the sera of females during estrogen therapy or pregnancy, where there was a gradual increase in density of the band at pH 4.25 and the appearance of an additional band at pH 4.15. In sera from patients with liver disease and elevated TBG levels, there was a fading of the acidic bands, whereas the more alkaline band at pH 4.55 was intensified. It is therefore proposed that microheterogeneity of TBG is caused by differences in NANA content and that variations of TBG patterns in native sera may reflect altered TBG synthesis or degradation. A genetically related microheterogeneity of TBG could not be demonstrated after examination of 800 sera, including 2 families with quantitative TBG deficiency