Methylphenidate (MPH) is the most preferred drug for treatment of the attention deficit hyperactivity disorder (ADHD). Here, we aimed to discuss the possible effects and mechanisms of MPH on precocious puberty (PP) via a case series with seven children who had normal body mass index. In this case series we evaluated seven children with ADHD, who had received MPH for at least 6 months (0.5 mg/kg/dose three times a day, maximum 60 mg) and admitted to Department of Pediatric Endocrinology with PP symptoms. The mean age was 8.16 years. Basal hormonal levels (luteinizing hormone [LH], follicle stimulating hormone, and estrogen/testosterone) were within normal range. Results of LH-releasing hormone stimulation tests demonstrated central pubertal responses. Glutamine, dopamine and noradrenaline are most important excitatory neurotransmitters that have a role at the beginning of puberty. The effect of MPH, cumulating dopamine and noradrenaline in the synaptic gap could be associated with the acceleration of puberty with the excitatory effect of dopamine’s gonadotropin-releasing hormone (GnRH) release, excitatory effect of noradrenaline’s GnRH release and the disappearance of GnRH receptor expression suppressor effect on prolactin disinhibitory effect.
Acceleration ; Adolescent ; Attention Deficit Disorder with Hyperactivity ; Body Mass Index ; Child ; Dopamine ; Endocrinology ; Follicle Stimulating Hormone ; Glutamine ; Gonadotropin-Releasing Hormone ; Humans ; Methylphenidate ; Neurotransmitter Agents ; Norepinephrine ; Prolactin ; Puberty ; Puberty, Precocious ; Receptors, LHRH ; Reference Values

Going back to basics prior to mentioning the use of antipsychotics in patients with pain, the International Association for the Study of Pain (IASP) definition of pain can be summarized as an unpleasant experience, composed of sensory experience caused by actual tissue damage and/or emotional experience caused by potential tissue damage. Less used than antidepressants, antipsychotics have also been used for treating this unpleasant experience as adjuvant analgesics without sufficient evidence from research. Because recently developed atypical antipsychotics reduce the adverse reactions of extrapyramidal symptoms, such as acute dystonia, pseudo-parkinsonism, akathisia, and tardive dyskinesia caused by typical antipsychotics, they are expected to be used more frequently in various painful conditions, while increasing the risk of metabolic syndromes (weight gain, diabetes, and dyslipidemia). Various antipsychotics have different neurotransmitter receptor affinities for dopamine (D), 5-hydroxytryptamine (5-HT), adrenergic (α), histamine (H), and muscarinic (M) receptors. Atypical antipsychotics antagonize transient, weak D₂ receptor bindings with strong binding to the 5-HT(2A) receptor, while typical antipsychotics block long-lasting, tight D₂ receptor binding. On the contrary, antidepressants in the field of pain management also block the reuptake of similar receptors, mainly on the 5-HT and, next, on the norepinephrine, but rarely on the D receptors. Antipsychotics have been used for treating positive symptoms, such as delusion, hallucination, disorganized thought and behavior, perception disturbance, and inappropriate emotion, rather than the negative, cognitive, and affective symptoms of psychosis. Therefore, an antipsychotic may be prescribed in pain patients with positive symptoms of psychosis during or after controlling all sensory components.
Affective Symptoms ; Analgesics ; Antidepressive Agents ; Antipsychotic Agents ; Delusions ; Dopamine ; Drug-Related Side Effects and Adverse Reactions ; Dystonia ; Hallucinations ; Histamine ; Humans ; Movement Disorders ; Norepinephrine ; Pain Management ; Prolactin ; Psychomotor Agitation ; Psychotic Disorders ; Receptor, Serotonin, 5-HT2A ; Receptors, Neurotransmitter ; Serotonin ; Weight Gain

OBJECTIVES: This study was aimed to investigate the association between amisulpride-induced hyperprolactinemia and the Taq1A polymorphism in the D2 dopamine receptor gene (DRD2) in schizophrenic patients. METHODS: The plasma concentrations of prolactin were measured before and after treatment with amisulpride in one hundred and twenty-five schizophrenic patients. The effect of the Taq1A variants of the DRD2 on the risk of amisulpride-induced hyperprolac-tinemia was the main the outcome measure. The genotyping for Taq1A (rs1800497) polymorphism was performed using TaqMan single nucleotide polymorphism (SNP) genotyping assay. RESULTS: There was a significant difference between the prolactin level at baseline and the 6th week after treatment with amisulpride in all the subjects. However, there were no significant correlations between ΔProlactin (the difference between prolactin level at baseline and the 6th week after treatment) and the Taq1A genotypes. CONCLUSIONS: This is the first study to investigate the-correlations between the Taq1A polymorphism and the amisulpride-induced hyperprolactinemia in Korean schizophrenic patients. The current results suggested the further large-scale researches on various SNPs in the DRD2 gene will establish clear goals and provide answers to the unanswered questions described in this study.
Dopamine* ; Genotype ; Humans ; Hyperprolactinemia* ; Outcome Assessment (Health Care) ; Plasma ; Polymorphism, Single Nucleotide ; Prolactin ; Receptors, Dopamine ; Receptors, Dopamine D2* ; Schizophrenia*

Menopause is a critical stage of women's life associated with various complaints and distresses. Vasomotor symptoms (VMS), such as hot flushes, night sweats, sleep disturbances, and fatigue, are the most common menopause symptoms affecting about 50% to 80% of middle-aged women. Obviously, these symptoms, resulting from estrogen deficiency during menopause, can exert negative effects on women's health and quality of life and thus require to be managed through approaches such as hormone replacement therapy (HRT). Many herbal treatments for menopause symptoms contain and its components such as 8-prenylnaringenin, 6-PN, isoxanthohumol and xanthohumol. Recent in-vivo studies have highlighted the ability of 8-prenylnaringenin to reduce serum-luteinizing hormone (LH) and follicle-stimulating hormone (FSH), to increase serum prolactin levels and uterine weight, and to induce vaginal hyperplastic epithelium. Previous research has shown that hops extract can strongly bind to both estrogen receptors, stimulate alkaline phosphatase activity in Ishikawa cells, and upregulate presenelin-2 and progesterone receptor mRNA in Ishikawa cells. Numerous clinical trials have documented significant reductions in the frequency of hot flushes following the administration of hop-containing preparations. Nevertheless, further clinical trials with larger sample size and longer follow-up are warranted to confirm such benefits.
Alkaline Phosphatase ; Epithelium ; Estrogens ; Fatigue ; Female ; Follicle Stimulating Hormone ; Follow-Up Studies ; Hormone Replacement Therapy ; Hot Flashes ; Humans ; Humulus* ; Menopause ; Prolactin ; Quality of Life ; Receptors, Estrogen ; Receptors, Progesterone ; RNA, Messenger ; Sample Size ; Sweat ; Women's Health

OBJECTIVETo investigate the effect of acupuncture on progesterone (P4) and prolactin (PRL) in rats of embryo implantation dysfunction (EID).

METHODSOn the first day of pregnancy, 72 female Wistar rats were randomly allocated into the normal group, the EID model group, the acupuncture group and the P4 group (18 in each group). The normal group was injected sesame oil, while the other three groups were given mifepristone to establish the EID model. The acupuncture group and the P4 group were given treatment of acupuncture and P4 injection, respectively. The serum of P4 and PRL were detected by radioimmunoassay, and the mRNA and protein expressions of P4 receptor (PR) and PRL receptor (PRLR) were detected using real-time polymerase chain reaction and immunohistochemical method, respectively.

RESULTSCompared with the normal group, the serum levels of P4 and PRL as well as the mRNA and protein expression levels of PR and PRLR in the EID model group were significantly lowered (P<0.01 or P<0.05). The above indices in the acupuncture group and the P4 group were significantly elevated compared with the EID model group (P<0.01 or P<0.05).

CONCLUSIONAcupuncture can promote embryo implantation effectively, which might be related to the effects of acupuncture on upregulating the P4 and PRL levels in serum and the PR and PRLR expression levels in rats.

Acupuncture Therapy ; Animals ; Embryo Implantation ; Endometrium ; metabolism ; Female ; Gene Expression Regulation ; Immunohistochemistry ; Male ; Pituitary Gland ; metabolism ; Pregnancy ; Progesterone ; blood ; Prolactin ; blood ; RNA, Messenger ; genetics ; metabolism ; Rats, Wistar ; Receptors, Progesterone ; genetics ; metabolism ; Receptors, Prolactin ; genetics ; metabolism

Prolactin is a polypeptide hormone which mainly acts on the reproductive system and plays an important role in penile erection and ejaculation. Prolactin receptors have a variety of short forms apart from the classic long form, which are widely expressed in male reproductive glands. High levels of prolactin can induce erectile dysfunction and results in secondary male infertility, which are mainly associated with the inhibition of dopaminergic activity, reduction of the testosterone level, and contraction of the cavernous smooth muscle. Moreover, low levels of prolactin can result in ejaculatory dysfunction. This article updates the views on the expressions of prolactin receptors in the male reproductive system, the effects of prolactin on penile erection and ejaculation, and its action mechanisms.
Ejaculation ; physiology ; Erectile Dysfunction ; Humans ; Infertility, Male ; Male ; Muscle, Smooth ; physiopathology ; Penile Erection ; physiology ; Prolactin ; physiology ; Receptors, Prolactin ; physiology ; Reproduction

BACKGROUNDProlactin (PRL) is a pituitary polypeptide hormone characterized by multiple biological actions including stimulation of growth in the prostate and formation of secretory alveoli and stimulation of milk protein gene expression in the mammary gland. PRL exerts its effect by dimerizing its receptor (PRLR) on the plasma membrane and regulating gene expression through the JAK-Stat signal pathway. We have previously described a natural variant of the PRLR in which the S2 subdomain of the extracellular domain is missing (Delta S2). Delta S2 PRLRs are dimerized in the absence of PRL and have constitutive activity in the promotion of breast cancer cell growth. Enhancer of zeste homolog 2 (EZH2), as one of the histone-modifying enzymes, is a key factor regulating gene expression by epigenetic modification. We hypothesized that these constitutive activated Delta S2 PRLRs played a pathogenic role in breast cancer in part through alterations in the expression of EZH2 and the trimethylation of histone 3 on lysine 27 (H3K27Me3).

METHODSIn order to verify the clinical significance and to establish the link between Delta S2 PRLR expression and epigenetic change, EZH2, H3K27Me3, and Delta S2 PRLR were detected in both normal and cancerous human breast tissues. Also, overexpression of Delta S2 PRLR in breast epithelial cells was achieved by infection with adenovirus carrying the cDNA. Western blotting and chromatin immunoprecipitation (ChIP assay) and acid histone extraction were applied to detect the expression of EZH2 and the trimethylation of histone 3, respectively.

RESULTSIn breast tissue, higher EZH2 expression and higher H3K27Me3 were found associated with higher Delta S2 expression in breast cancer samples. In breast epithelial cells, overexpression of Delta S2 PRLR increased EZH2 methyltransferase mRNA and protein, induced EZH2 methyltransferase recruitment to chromatin, increased the trimethylation of H3K27Me3, and decreased the expression of p53 gene.

CONCLUSIONSDelta S2 PRLR plays an important pathogenic role in breast cancer through epigenetic modification. Elevated expression of Delta S2 PRLR, achieved by alternate splicing of the pre-mRNA of the full-length form, is a new mechanism contributing to human breast cancer.

Breast Neoplasms ; metabolism ; Enhancer of Zeste Homolog 2 Protein ; Female ; Gene Expression Regulation, Neoplastic ; Histones ; metabolism ; Humans ; MCF-7 Cells ; Polycomb Repressive Complex 2 ; metabolism ; Receptors, Prolactin ; metabolism ; Tumor Suppressor Protein p53 ; metabolism

Blonanserin is a newly developed agent which is approved for the treatment of schizophrenia in Japan and Korea. This agent has high affinity to dopamine D2 receptor and serotonin 5-HT2A receptor. Blonanserin was as effective as risperidone in the treatment of schizophrenia, and showed greater efficacy in negative symptoms than haloperidol. Blonanserin was well tolerated in both the short- and long-term studies, and the frequency and intensity of EPS is generally similar with risperidone. For other side effects, blonanserine seems to have better safety profiles compared with other atypicals, and showed less prolactin elevation than risperidone. These findings suggest that blonanserin is useful in the treatment of schizophrenia.
Haloperidol ; Japan ; Korea ; Piperazines ; Piperidines ; Prolactin ; Receptor, Serotonin, 5-HT2A ; Receptors, Dopamine D2 ; Risperidone ; Schizophrenia ; Serotonin

OBJECTIVETo investigate the correlation of prolactin receptor (PRL-R) expression to estrogen receptor (ER) and progesterone receptor (PR) expressions in primary breast cancer.

METHODSFor 130 female patients with breast cancer (median age 46 years), PRL-R expression in the primary tumor was detected by immunohistochemistry, and the correlation between PRL-R and ER/PR expressions was analyzed statistically.

RESULTSPRL-R positivity in the primary tumor was found in 89 of the patients (68.5%), and the positivity rate for PRL-R was positively correlated to ER expression (P<0.05). Further stratification of the patients according to the CerbB-2 status revealed such a correlation only in CerbB-2-positive patients (P<0.05). In the patient cohort, no significant correlation was found in the positivity rate between PRL-R and PR expressions (P>0.05), but in CerbB-2-positive patients, the positivity rate of PRL-R showed a positive correlation to PR expression (P<0.05).

CONCLUSIONThe positive correlations in positivity rate between the PRL-R and ER/PR expressions are found only in CerbB-2 positive patients with breast cancer, and the expressional status of CerbB-2 affects the correlation between PRL-R and ER/PR expression in breast cancer.

Adult ; Aged ; Breast Neoplasms ; metabolism ; Female ; Humans ; Middle Aged ; Receptor, ErbB-2 ; genetics ; metabolism ; Receptors, Estrogen ; metabolism ; Receptors, Progesterone ; metabolism ; Receptors, Prolactin ; metabolism

PURPOSE: The purpose of this study was to identify differences in signal transduction gene expression between normal and diabetic keratocytes stimulated with interleukin-1alpha (IL-1alpha) and tumor necrosis factor-alpha (TNF-alpha). METHODS: Normal and diabetic keratocytes were primarily cultured and treated with 20 ng/ml IL-1alpha and TNF-alpha for 6 h. cDNA was hybridized to an oligonucleotide microarray. Genes identified by the microarray were further evaluated by real-time PCR. RESULTS: Diabetic keratocytes over-expressed components of the MAPK and Notch pathways, and under-expressed components of the insulin, calcium, and TGF-beta pathways. Cytokine treated diabetic keratocytes differentially expressed components of the TGF-beta and MAPK pathways. After IL-1alpha and TNF-alpha treatment, nine genes were under-expressed, falling in the insulin, TGF-beta, and Toll-like receptor pathways. Real-time PCR showed a significant decrease in the IL-6 and TGF-beta2 genes and a significant increase in the Ppm1a gene. CONCLUSIONS: There were some differences in gene expression between normal and diabetic keratocytes related to signal transduction pathways, such as the insulin, MAPK, calcium, and TGF-beta pathways. In addition, IL-1alpha and TNF-alpha stimulating the insulin, TGF-beta, and Toll-like receptor signaling pathways may have different effects in diabetic keratocytes.
Animals ; Apoptosis ; Cells, Cultured ; Cornea/drug effects/*metabolism/pathology ; DNA/*genetics ; Diabetes Mellitus, Experimental/*genetics/pathology ; Gene Expression Profiling ; Insulin/genetics ; Interleukin-1alpha/pharmacology ; Mitogen-Activated Protein Kinase Kinases/genetics ; Nuclear Proteins/genetics ; Oligonucleotide Array Sequence Analysis/*methods ; Phosphoric Monoester Hydrolases/genetics ; Polymerase Chain Reaction ; Prolactin/genetics ; Rats ; Rats, Long-Evans ; Receptors, Notch/genetics ; Signal Transduction/drug effects/*genetics ; Transforming Growth Factor beta/genetics ; Tumor Necrosis Factor-alpha/pharmacology ; Ubiquitin-Protein Ligases/genetics