The role of prolactin/vasoinhibins in cardiovascular diseases

Prolactin(PRL)is a polypeptide hormone that is mainly synthesized and secreted by the lactotroph cells of the pituitary.There are two main isoforms of PRL:23-kDa PRL(named full-l ength PRL)and vasoinhibins(including 5.6–18 kDa fragments).Both act as circulating hormones and cytokines to stimulate or inhibit vascular formation at different stages and neovascularization,including endothelial cell proliferation and migration,protease production,and apoptosis.However,their effects on vascular function and cardiovascular diseases are different or even contrary.In addition to the structure,secretion regulation,and signal transduction of PRL/vasoinhibins,this review focuses on the pathological mechanism and clinical significance of PRL/vasoinhibins in cardiovascular diseases.

Body Composition, Gynecologic-Obstetric Variables, and Prolactin Levels in Patients with Breast Cancer

Objective: The aim of this study was to determine body composition, gynecological, and obstetric data, sex hormones, and prolactin serum levels in pre- (PREW) and postmenopausal women (PMW) with breast cancer (BC) and compare them with a control group (CG) of healthy women. Methodology: BC patients without treatment or use of hormone replacement therapy, or hormonal birth control, and without data of metastasis were included. CG was matched for age, BMI, and menstrual cycle status. FSH, LH, E2, progesterone, testosterone, and prolactin (PRL) were measured using radioimmunoassay kits. Comparisons between BC and CG were made with “t” tests, and with the Mann-Whitney U-test;χ2 test was used to compare the qualitative variables between the groups. Results: Seventy-two patients with BC, and 74 CG women were evaluated. Both groups presented overweight data, BMI (kg/mt2) = 27.21 ± 5.51 vs. 28.40 ± 4.66, p = ns, for BC patients and CG, respectively. In PREW, the age at menarche was later in BC patients compared to the CG (13.3 ± 1.36 years vs. 12.41 ± 1.27 years, p = 0.005). The PMW with BC presented a higher age at menarche and menopause compared to the women of the CG (13.51 ± 1.48 vs. 12.91 ± 1.41, p = 0.09, and 49.03 ± 2.86 vs. 45.5 ± 8.78, p = 0.03, respectively). PRL levels were significantly higher in PMW with BC, in comparison with the CG;median and minimum and maximum values (min-max) were: 14.7 ng/mL (3.6 - 52.7) vs. 5.9 ng/mL (1.9 - 33.3), p = 0.005). A higher percentage of PMW with BC (26.0% vs. 7.1%, χ2 = 5.57, p = 0.01) presented hyperprolactinemia (PRL serum levels > 20 ng/mL), compared to the GC. Conclusions: The higher levels of PRL in PMW with BC compared with CG, suggest a proliferative effect of this hormone in the affected breast tissue. This study demonstrates the need to use biological markers such as PRL to determine the risk of BC in PMW.

Exploring the pathogenesis of idiopathic granulomatous mastitis based on the prolactin theory

Prolactin(PRL),as a cytokine,plays a variety of multidirectional roles in immunity and inflammation.An autoimmune condition known as idiopathic granulomatous mastitis(IGM)involves many inflammatory cells and cytokines.PRL links neuroendocrine and immune systems and plays an active role in the inflammatory and immune processes.Based on the theory of PRL and combined with the latest research review at home and abroad,this paper aims to review the mechanism of action of PRL on IGM from the aspects of various inflammatory cells,cytokines and pathways,revealing the influence of PRL theory on IGM and the mechanism of action,so as to effectively control inflammation in the long-term.

Expression of Prolactin Gene in Rat Prolactinoma Induced by 17-β-Estradiol

Rats were implanted subcutaneously with silastic capsules containing 10 mg 17-β-estradiol. After 30, 60 and 120 days, their pituitary weights and plasma PRL levels were found to increase significantly. The administration of β-estradiol also produced a marked rise of PRL mRNA concentrations in the rat total RNA, but the sharper rise of serum PRL levels indicates that estradiol not only promotes transcription of prolactin gene, but also improves the efficiency of translation of the transcription product.

The brain as a source and a target of prolactin in mammals

Prolactin is a polypeptide hormone associated with an extensive variety of biological functions.Among the roles of prolactin in vertebrates,some were preserved throughout evolution.This is the case of its function in the brain,where prolactin receptors,are expressed in different structures of the central nervous system.In the brain,prolactin actions are principally associated with reproduction and parental behavior,and involves the modulation of adult neurogenesis,neuroprotection,and neuroplasticity,especially during pregnancy,thereby preparing the brain to parenthood.Prolactin is mainly produced by specialized cells in the anterior pituitary gland.However,during vertebrate evolution many other extrapituitary tissues do also produce prolactin,like the immune system,endothelial cells,reproductive structures and in several regions of the brain.This review summarizes the relevance of prolactin for brain function,the sources of prolactin in the central nervous system,as well as its local production and secretion.A highlight on the impact of prolactin in human neurological diseases is also provided.

The Role of Prolactin in the Evolution of Prostate Cancer

Today there is significant information indicating an effect of prolactin on the prostate gland. It has been shown to be involved in mechanisms leading to the synthesis of some proteins such as PSA and cathepsin D, synthesis of citrate and accumulation of zinc. Also, at the behavioral level, prolactin is known to control some aspects of reproduction, including documentation on the physiology of the prostate and the possibility to trigger pathologies in this sex gland. Although the later still is not clear, there is a correlation between the level of prolactin and the presence of prostate pathologies. Thus, the aim of this review is to show how prolactin is involved in the progression of some pathologies of this male sexual gland.

Gender Differences in Serum Prolactin Levels in Drug Naïve First Episode Schizophrenia

Objective: To determine if there is a significant rise in serum prolactin (PRL) in acute psychosis related to disease process and weather there is a significant gender difference in the level of PRL and its correlation psychopathology. Procedure: Naturalistic study involved 60 consenting outpatients and inpatients in a tertiary psychiatric setting. Patient base was comprised of men (n?= 30) and women (n?= 30) with 83% in the age range of 21 - 40 years old. All subjects had confirmed first episode diagnosis set forth by the Diagnostic and Statistical Manual of Mental Disorders. Patients were drug free and drug na?ve. Standardization for control was done using 15 control PRL samples obtained from healthy individuals. Methodology involved assessment by radioimmunoassay, the Brief Psychiatric Rating Scale and the Positive and Negative Syndrome Scale at day 1, 3 weeks and again at 6 weeks. All patients were treated with atypical antipsychotic drugs. Results: Serum PRL was elevated on baseline in 75% of first episode psychosis schizophrenia, yet found to have a negative correlation to psychopathology at base week 3 and week 6 samples. Conclusions: Elevated serum PRL is not a potential indicator of acute schizophrenia. Levels are higher in females than in males, yet females respond better to treatment at a lower dose than males.

BMP-4 accelerates PRL secreting,cell proliferation and invasiveness in human prolactinoma

Objective： The aim of the study was to explore the bone morphogenetic protein 4 （BMP-4） how to regulate pro- lactin （PRL） secreting, cell proliferation and invasiveness in human prolactinorna. Methods： Ten patients who diagnosed as prolactinoma by clinical characteristics and pathology were divided into two groups, one was sensitive to Brornocriptine, the other was insensitive to Brornocriptine. Every case was conducted by primal cell culture then treated by different concentrations of BMP-4. The cell configuration was observed and PRL hormone was measured in different times. The expressions of BMP-4 rnRNA and BMP-4 in 37 cases of prolactinorna and 8 cases of normal pituitary tissues samples were detected by immunohistochemical and in situ hybridization technique, and the results were analyzed by statistic methods. Results： BMP-4 （5 ng/rnL） could accelerate the secreting of PRL in prolactinorna cell, and it could reach the greatest effect in the concentration of 20 ng/mL. BMP-4 could increase prolactinoma cell proliferation, but when the concentration was 50 ng/rnL, the BMP-4 effect of increasing secreting decreased. When 100 ng/mL, the cell began to die. The effects of the BMP-4 in sensitive group and insensitive group had no difference. The BMP-4 was highly expressed in the prolactinornas and was positively related with the invasiveness grades. Conclusion： BMP-4 have positive regulation in prolactinoma secreting, proliferation, invasiveness effects, BMP-4 probably has the important role in prolactinoma pathogenesis.

An Association of Elevated Serum Prolactin with Phthalate Exposure in Adult Men

Objective To investigate the associations of hormone circulation with phthalate exposure in adult men. Methods Semen and serum samples were collected from 118 men who were suspected of infertility. Phthalate diesters including dibutyl phthalate （DBP） and diethylhexyl phthalate （DEHP） in both semen and serum samples were measured, along with serum levels of follicle stimulating hormone （FSH）, luteinizing hormone （LH）, testosterone （T）, estradiol （E 2 ） and prolactin （PRL）. Results Serum PRL was positively associated with serum DBP and DEHP and semen DEHP in all models of Spearman correlation, linear regression and binary logistic regression. In linear regression models adjusted for potential confounders and excluding subjects with undetectable phthalates, a 10‐fold increase in semen DEHP was associated with a 23% increase in serum PRL, as well as a 26% increase in serum DBP and a 20% increase in serum DEHP. In logistic regression models all subjects demonstrated a dose‐response relationship between above reference value PRL and semen DEHP （odds ratio per tertile adjusted for potential confounders = 1.0, 1.70, 3.50; P for trend = 0.01）, and serum DBP （1.0, 1.10, 2.62; P for trend = 0.04）, and serum DEHP （1.0, 1.46, 4.69; P for trend 0.01）. A positive correlation between serum estradiol and semen DEHP （linear regression）, and an inverse correlation between semen DBP and serum testosterone and T：E 2 ratio （Spearman correlation） were also established. Conclusions Serum PRL is suggested to be positively associated with both DBP and DEHP exposure in adult men.

Expression of prolactin receptor and response to prolactin stimulation of human NK cell lines

We have previously shown a critical role of prolactin (PRL) during maturation and anti-tumor effects of murine natural killer (NK) cells in vitro and in vivo. We extended that study by exploring the ability of human NK cell lines (NK-92 and YT cell) to express PRL receptor (PRL-R) and to respond to PRL stimulation in vitro. Both human NK cell lines constitutively expressed PRL-R on membrane and mRNA transcripts,NK-92 cells contained higher level of PRL-R than YT cells,which correlated to the enhanced capacity of the cells to proliferate and to lyse target cells in response to PRL stimulation in the presence of trace amount of IL-2 or IL-15 in vitro. Two differences between IL-2 and IL-15 in functioning on human NK cells were for the first time observed. PRL synergized with IL-15 to improve proliferation of NK cells in a dose-dependent manner without double peak manifesting like IL-2. Although PRL enhanced the cytotoxicity of IL-2 or IL- 15 activated NK cells,it exerted the function through up-regulating gene expression of perforin without influence of FasL in IL-2-stimulated NK cells,while in IL-15-stimulated NK cells,PRL did the function through up-regulating gene expression of both perforin and FasL but not IFNγ. PRL increased expressions of IL-2Rα on membrane and of IL-2 mRNA in cells,indicating that PRL up-regulated NK cell function by improving positive feedback between IL-2 and IL-2R. The similar results were also observed in network between IL-15 and IL-15R. These data indicate a potential role of PRL in human NK cell modulation.

Adjunctive aripiprazole for antipsychotic-related hyperprolactinaemia in patients with first-episode schizophrenia:a metaanalysis

Background Hyperprolactinaemia is a common antipsychotic(AP)-induced adverse effect,particularly in female patients.Aims This meta-analysis examined the efficacy and safety of adjunctive aripiprazole in preventing AP-related hyperprolactinaemia in patients with first-episode schizophrenia.Methods PubMed,PsycINFO,EMBASE,Cochrane Library,WanFang and China Journal Net databases were searched to identify eligible randomised controlled trials(RCTs).Primary outcomes were the reductions of serum prolactin level and prolactin-related symptoms.Data were independently extracted by two reviewers and analysed using RevMan(V.5.3).Weighted/standardised mean differences(WMDs/SMDs)±95%Cis were reported.Results In the five RCTs(n=400),the adjunctive aripiprazole(n=197)and the control groups(n=203)with a mean of 11.2 weeks of treatment duration were compared.The aripiprazole group had a significantly lower endpoint serum prolactin level in all patients(five RCTs,n=385;WMD:-50.43 ng/mL(95%Cl:-75.05 to-25.81),p<0.00001;l2=99%),female patients(two RCTs,n=186;WMD:-22.58 ng/mL(95%Cl:-25.67 to-19.49),p<0.00001;l2=0%)and male patients(two RCTs,n=127;WMD:-68.80 ng/mL(95%Cl:-100.11 to-37.49),p<0.0001).In the sensitivity analysis for the endpoint serum prolactin level in all patients,the findings remained significant(p<0.00001;l2=96%).The aripiprazole group was s叩erior to the control group in improving negative symptoms as assessed by the Positive and Negative Syndrome Scale(three RCTs,n=213;SMD:-0.51(95%Cl:-0.79 to-0.24),p=0.0002;l2=0%).Adverse effects and discontinuation rates were similar between the two groups.Conclusions Adjunctive aripiprazole appears to be associated with reduced AP-induced hyperprolactinaemia and improved prolactin-related symptoms in first-episode schizophrenia.Further studies with large sample sizes are needed to confirm these findings.

Prolactin and risk of preeclampsia: A single institution, cross-sectional study

Objective: To illustrate the association between prolactin serum level and severity of preeclampsia. Methods: In this cross-sectional study, 31 pregnant women with preeclampsia were enrolled as GroupⅠand 20 healthy pregnant women as GroupⅡ. Routine investigations and prolactin serum levels were assessed together with blood pressure changes. The unpaired t-test was used to determine the differences and correlation coefficient for the evaluation of correlation. Results: Prolactin serum levels were higher in preeclampsia patients compared with those of the healthy pregnant women (P<0.001). The severity of preeclampsia was linked with prolactin serum levels since 20 patients with preeclampsia showed mild preeclampsia that illustrated relatively lower prolactin serum levels compared with 11 patients with severe preeclampsia (P<0.001). The severity of mean arterial blood pressure was significantly correlated with prolactin serum levels (r=0.78, P<0.001). Conclusions: Prolactin serum levels are elevated in patients with preeclampsia and correlated with the severity of preeclampsia. High but not normal prolactin might be implicated in the pathogenesis of preeclampsia.

The Effects of Insulin and Prolactin on an Epithelial Cell Line from Mammary Gland of Dairy Goat

Mammary epithelial cells with lactational function can be a valuable cellular model for research of the development and regulation of the mammary gland.This paper describes some aspects of function of an epithelial cell line from the mammary gland of the dairy goat.SDS-PAGE,triglyceride and lactose content of cultured cells were used to assess synthetic function of cells and the effects of exposure to insulin and prolactin.Results show that goat mammary epithelial cells can synthesize fat,proteins and lactose when they were cultured in DMEM-F12 medium with added EGF,IGF-1,ITS and FBS.There were no obvious changes after 48h treatment with additional insulin.Prolactin added to the basal medium significantly increased synthesis of proteins and lactose.A mammary gland epithelial cell line from goats which has lactational function has been established.This outcome provides a valuable and convenient model system.

Reversing the negative effects of co-inhaled manganese and iron on dopamine levels and prolactin production in the rat hypothalamus-pituitary axis

BACKGROUND： Manganese （Mn） and iron （Fe） are the primary elements of welding rods. Mn has been shown to increase prolactin （PRL） production by decreasing dopamine （DA） levels in the hypothalamus. However, Fe increases DA levels and decreases PRL levels. The toxic mechanism of Mn and Fe co-inhalation-induced regulation of the hypothalamic-hypophyseal-pituitary axis remains unclear. OBJECTIVE： To evaluate the effects of co-inhaled Mn and Fe on hypothalamic DA levels and pituitary PRL production, to investigate whether these changes are reversible, and to determine the role of co-inhaled Mn and Fe. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment based on inhalation toxicity via whole-body exposure was performed. Hypothalamic DA levels, serum PRL, and PRL and PiN mRNA levels were analyzed at the Institute of Environmental and Occupational Medicine, Inje University, Busan, Korea, from August 2007 to May 2009. MATERIALS： MnSO4 and FeSO4 were purchased from Sigma-Aldrich, St. Louis, MO, USA. High-performance liquid chromatography （HPLC） using an electrochemical detector （ECD） was purchased from Waters Corporation, Milford, MA, USA. mRNA Capture Kit and reverse transcription-polymerase chain reaction （RT-PCR） kit were obtained from Roche Molecular Biochemicals, Mannheim, Germany and Perkin-Elmer, Wellesley, MA, USA, respectively. Rat PRL enzyme-linked immunosorbent assay kit was purchased from Biocode Hycel, Liege, Belgium. METHODS： Eighty 15-week-old, male, Fischer 344 rats were assigned to two groups： one group treated with Mn and Fe and a control group. Each group was sub-divided into four groups on the basis of treatment period （0- and 13-week treated groups with both chemicals） and recovery periods （4- and 13-week recovery groups following 13-week exposure to both chemicals）. The treatment condition was 6 hours per day, 5 days per week, for the entire body. Mn and Fe co-inhalation concentrations were 1.5 mg/m3 and 3.0 mg/m3, respectively. MAIN OUTCOME MEASURES： Hypothalamic DA levels were measured using HPLC-ECD analysis mRNA levels of PRL and Pit-1 were analyzed by Northern blot hybridization and RT-PCR, respectively. Serum PRL levels were measured by enzyme-linked immunosorbent assay. RESULTS： HPLC-ECD analysis revealed that following 13-week co-inhalation of Mn and Fe, hypothalamic DA levels significantly deceased, whereas pituitary PRL mRNA, Pit-1 mRNA, and serum PRL levels significantly increased. At 4 weeks of recovery, DA level in the hypothalamic tissue was significantly increased, and PRL and Pit-1 mRNA levels in the pituitary were significantly decreased. After 13 weeks of recovery, DA and PRL levels recovered to normal. The changing pattern of serum PRL levels was in accordance with pituitary PRL mRNA levels. CONCLUSION： Subchronic co-inhalation of Mn and Fe significantly decreased hypothalamic DA levels, but induced pituitary PRL production, both of which were mediated by Pit-1. These results suggested that Mn dominates over Fe in terms of hypothalamic DA levels and pituitary PRL production, and these effects are reversible in a subchronic inhalation condition. Therefore, changes in hypothalamic DA levels and serum PRL production could be used as biomarkers for welders, who are exposed to Mn and Fe.

Relationship Between Effect of Electro-Acupuncture on Prolactin Secretion and Several Central Neurotransmitters

We have reported that the central mechanism of acupuncture-induced PRL secretion in non-lactating rats are related to antagonizing hypothalamic dopamine activity; noradrenaline system played little significant role in the acupuncture effect; Υ-aminobutyric-acid system perhaps participated in this effect.This paper further provided evidence that central serotonin and EOP play a stimulatory role in the acupuncture induced secretion of prolactin; acupuncture may antagonize inhibitory effect of H2 histamine receptor activation on prolactin secretion; the possible role of H1-receptor needs further investigation.

Ultrastructural and Immunoelectron Microscopical Study of Human Pituitary Somatotroph Adenomas and Prolactinomas

Nowdays the application of immunohistochemical techniques and ultrastructuralanalysis and correlation with clinical and biochemical findings have led to a moredetailed functional classification,in which growth hormone (GH)-producing andprolactin (PRL)-producing adenomas have been shown to comprise more than halfof pituitary adenomaso.Few immunoelectron microscopic studies on GH and PRLadenomas have been made,however,in limited cases so far,though a numberof authors have described the characteristics of pituitary adenomas by conventionalelectron microscopy.In addition to routine electron microscopy,immuno-.electron microscopical technique using protein A-gold probes was applied in

Measurement of Prolactin and Estradiol to Estimate Menses Return of Breastfeeding Mothers

Objective To determine whether the measurement of serum prolactin (PRL) and estradiol (E2) is effective and reliable to estimate the returning time of menses during breastfeedingMethods Serum PRL and E2 were measured in 703 breastfeeding mothers during the period of <2 , > 2, 3, 4, 5 and 6- 9 months postpartum. Radio-immunoassay (RIA) was used to measure the levels of PRL and E2. The cervical mucus, sexual behaviors and vagina bleeding were also monitored since 56 d after postpantum. Results (1) The average level of serum PRL and E2was 8. 16, 3. 66, 0. 69 in the fully breastfeeding, mixed-feeding and bottle-feeding groups respectively. It showed that 92. 55% mother returned menses -within 6 months of postpartum in the bottle-feeding group. (2) According to the results, the levels of serum Prolactin and Estradiol were related to the feeding ways, but not completely related to the duration of postpartum. (3) By using the ratio of PRL to E2to estimate the time of menses return among the breastfeeding mothers, we found that when the ratio became 0. 60, the subjects' menses would returen. .The sensitivity and the specificity of this method were 89. 85% and 90. 68% respectively.Conclusion The measurement of serum PRL and E2is a simple, effective and reliable method to estimate the return time of menses during breastfeeding period. If possible, it should be promoted for clinical use to prepare for their fertility return.

Plasma levels of luteinizing hormone and prolactin in relation to double brooding in Great Tit(Parus major)

The reproductive behaviors of birds are mainly controlled by the hypothalamus-pituitary-gonad axis.Many studies have shown that reproductive hormones are tightly linked to the breeding sub-stages.However,only a few studies have examined the temporal trend of hormone levels among different reproductive stages in multiple brooded species.We investigated the changes in plasma luteinizing hormone(LH)and prolactin(PRL)concentrations during different reproductive stages of the facultative double-brooded Great Tit(Parus major).We found that the concentrations of LH and PRL in females were significantly higher than those in males.Females had significantly higher LH and lower PRL concentrations in the pre-breeding period than in the first/second brooding periods,and there were no significant changes between the first and second brooding periods.The concentrations of LH and PRL in males had no significant difference between the pre-breeding period and the first brooding periods,while LH and PRL concentrations in the second brooding period were significantly higher than those in the first brooding period.We conclude that there are sex-based differences between LH and PRL at different stages of reproduction.The changes in LH and PRL in both males and females should be related to their physiological functions.Especially for males,individuals with higher levels of LH and PRL are more likely to maintain second clutches.

Proteomic Analysis of Nuclear Phosphorylated Proteins in Dairy Cow Mammary Epithelial Cells Treated with Prolactin

Prolactin （PRL） is a versatile signaling molecule and regulates a variety of physiological processes, including mammary gland growth and differentiation and the synthesis of milk proteins. While PRL is known to be necessary for high levels of milk protein expression, the mechanism by which the synthesis of milk proteins is stimulated at the transcript level is less known. A major modification in the transcript level is protein phosphorylation. To gain additional insights into the molecular mechanisms at the transcript level underlying PRL action on the dairy cow mammary epithelial cells （DCMECs）, nuclear phosphoproteins whose expression distinguishes proliferating regulated by PRL in DCMECs were identified. A phosphoprotein-enriched fraction from nuclear proteins was obtained by affinity chromatography, and a two-dimensional gel electrophoresis （2-DE） and matrix assisted laser desorption/ionization time of matrix-assisted laser desorption/ionization/time of flight mass spectrometry （MALDI-TOF MS） were used to identify the changes of nuclear phosphoproteins in DCMECs treated with prolactin. Seven proteins displaying~〉2-fold difference in abundance upon PRL treatment in DCMECs were identified by MALDI-TOF MS. The protein-GARS （GlyRS）, which belonged to the class-II aminoacyl-tRNA synthetase family, played a global role in the milk protein synthesis. SERPINH1 （Heat shock protein 47）, which was the first heat shock protein found to be a member of the serpin superfamily, regulated physiologic functions, such as complement activation, programmed cell death, and inflammatory processes. PRDX3, which belonged to a family of antioxidant enzymes, played an important role in scavenging intracellular reactive oxygen species （ROS）. ACTR1A, belonged to the actin family, which was associated with transport of p53 to the nucleus. Annexin A2, a Ca2＋-dependent phospholipid-binding protein, maintained the viability and cell cycle regulation of DCMECs. PSMB2 and PSMD10, which belonged to ubiquitin-proteasome system, were involved in several cellular processes, including cell cycle control, cellular stress response, intracellular signaling. This screening revealed that prolactin influenced the level of nuclear phosphoproteins in DCMECs. This result opens new avenues for the study of the molecular mechanism linked to the synthesis of milk proteins.

Tinospora cordifolia attenuates antipsychotic drug induced hyperprolactinemia in Wistar rats

Objective: To evaluate the anti-hyperprolactinemic effect of methanolic extract of Tinospora cordifolia against antipsychotic/neuroleptic drug induced hyperprolactinemia. Methods: A total of 48 Wistar albino rats were chosen in the study. To induce hyperprolactinemia, haloperidol at 5 mg/kg/day was intraperitoneally administered for 16 continuous days and sulpiride at 20 mg/kg/day was administered intraperitoneally for 28 continuous days. Methanolic extract of Tinospora cordifolia at 200 mg/kg/day and 400 mg/kg/day were administered orally 30 min before administration of haloperidol and sulpiride for 16 and 28 days, respectively. Then, we had evaluated prolactin, dopamine and antioxidant status in the treatment group as compared to haloperidol and sulpiride. Results: There was a significant (P<0.05) increase in serum prolactin level and decrease in dopamine level in the haloperidol and sulpiride treated animals. However, methanolic extract of Tinospora cordifolia significantly (P<0.05) decreased serum prolactin level and increased brain dopamine level. Further, superoxide dismutase and catalase level were also decreased significantly in the haloperidol and sulpiride treated groups as compared to those of the control group and the antioxidant status was restored significantly on treatment with methanolic extract of Tinospora cordifolia. Furthermore, methanolic extract of Tinospora cordifolia also reduced total leukocyte count, and increased red blood cell count and hemoglobin concentration. In addition, the spleen did not show signs of infection or inflammation in the experiments. Conclusions: Methanolic extract of Tinospora cordifolia has a significant anti-hyperprolactinemic effect which may be attributed to neuroprotective and antioxidant effects of its signature constituents like stepharanine.