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Case Reports 2011; 32(5): 616-618 PubMed PMID: 22167128 Citation  Keywords:  Adult, Amenorrhea:blood, Appetite Depressants:adverse effects, Cyclobutanes:adverse effects, Diagnosis, Differential, Female, Galactorrhea:blood, Humans, Hyperprolactinemia:blood, Prolactin:blood, Weight Gain:drug effects,.   

INTRODUCTION: Several drugs may cause hyperprolactinemia, especially antipsychotic drugs and prokynetic drugs. Serum prolactin concentrations increase within hours after acute administration of these drugs and return to normal within two to four days after cessation of chronic therapy. So far, sibutramine, a sympathomimetic drug used in the management of obesity, was not described to be associated with altered prolactin levels.

OBJECTIVE: The purpose of this study is to present a case of sibutramine-induced hiperprolactinemia.

CASE REPORT: A 38-year-old white female patient seeks medical attention complaining of weight gain (Body mass index: 35) associated with anxiety. She started sibutramine treatment and presented with amenogalactorrhea. Hyperprolactinemia was diagnosed (prolactin of 46 and 89.6 ng/mL) with normal thyroid, renal and hepatic function, and a negative pregnancy test. A sella MRI was performed and sibutramine was suspended. Prolactin levels returned to normal within 15 days of sibutramine cessation and remained normal within 90 days of follow-up, with resolution of the amenogalactorrhea syndrome.

CONCLUSION: sibutramine may be considered in differential diagnosis of drug-induced hyperprolactinemia....

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Comparative Study 2011; 32(4): 428-436 PubMed PMID: 21876517 Citation  Keywords:  Adult, Anthropometry, Antipsychotic Agents:adverse effects, Benzodiazepines:adverse effects, Blood Glucose:drug effects, Clozapine:adverse effects, Female, Glucose Intolerance:chemically induced, Humans, Hyperprolactinemia:chemically induced, Insulin Resi.   

OBJECTIVES: This study consisting of two subprojects was undertaken to evaluate the effects of hyperprolactinemia on cardiovascular disease (CVD) risk parameters such as anthropometric measures, insulin sensitivity and blood lipids in patients with schizophrenia or related psychoses on long term treatment with antipsychotics.

METHODS: In subproject Ι, 45 patients receiving the 2nd generation antipsychotics risperidone, clozapine or olanzapine were compared regarding prolactin (PRL), body mass index (BMI), insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and blood lipids. In subproject Π, 24 patients receiving 1st or 2nd generation antipsychotics were investigated with diurnal profile of PRL and oral glucose tolerance test (OGTT).

RESULTS: Elevated PRL levels were found in about 45% of the patients and occurred more often in patients receiving risperidone or haloperidol, compared to patients receiving clozapine or olanzapine. In contrast, in subproject Ι, insulin and HOMA-IR were higher and high density lipoprotein cholesterol was lower in patients receiving clozapine or olanzapine, compared with patients receiving risperidone. However, PRL levels did not correlate to BMI, insulin, HOMA-IR or lipids in any of these three treatment groups. In subproject Π, OGTT showed impaired glucose tolerance in 25% and new-onset diabetes in 4% of the 24 patients investigated. Additionally, the PRL (median 24 h) levels correlated positively to the 2 h glucose level at OGTT (rs=0.42, p=0.04).

CONCLUSIONS: Our findings point to that hyperprolactinemia due to 1st and 2nd generation antipsychotics may decrease insulin sensitivity, whereas other mechanisms probably underlie insulin resistance induced by PRL-sparing antipsychotics such as clozapine and olanzapine....

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Journal Article 2011; 32(2): 170-175 PubMed PMID: 21552201 Citation  Keywords:  Animals, Cell Proliferation:drug effects, Dopamine:metabolism, Dose-Response Relationship, Drug, Ethanol:pharmacology, Female, Glutamic Acid:metabolism, Hypothalamus:drug effects, Models, Animal, Neurotransmitter Agents:metabolism, Norepinephrine:metaboli.   

OBJECTIVES: Alcohol induces hyperprolactinemia in both alcoholic men and women, but the mechanism is not fully established. The aim is to investigate the mechanism involved in elevation of serum prolactin level after chronic alcohol administration.

METHODS: In this study, healthy female SD rats were given alcohol for 8 weeks and checked for serum prolactin level by radioimmunoassay. Interior pituitary cell proliferation was determined by immunohistochemistry score of Ki-67, and hypothalamic neurotransmitters were detected by Coulomb HPLC electrochemical array.

RESULTS: We demonstrated that serum prolactin level and wet pituitary weight of alcohol-fed rats were significantly increased. Interior pituitary cell proliferation was significantly enhanced; hypothalamic dopamine, 5-HT and GABA levels were reduced while glutamate level was increased by chronic alcohol administration; hypothalamic noradrenalin level remained unchanged.

CONCLUSION: Our study suggested that chronic alcohol administration resulted in elevated serum prolactin level in normal SD rats probably through enhancing pituitary gland cell proliferation combined with altered hypothalamic neurotransmitters that regulate prolactin level....

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Journal Article 2010; 31(6): 782-791 PubMed PMID: 21196914 Citation  Keywords:  2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine:pharmacology, Animals, Benzazepines:pharmacology, Blotting, Western, CREB-Binding Protein:metabolism, Cell Proliferation:drug effects, Dopamine Agonists:pharmacology, Dopamine Antagonists:pharmaco.   

OBJECTIVE: Dopamine exists in the immune system and has obvious immunomodulating action. However, receptor mechanism underlying the dopamine immunomodulation remains to be clarified. In the present study, we provide the evidence for existence of dopamine receptor subtypes in T lymphocytes and show the roles of the receptors and the receptor-coupled signaling in mediating the dopamine immunomodulation.

METHODS: The purified T lymphocytes from the mesenteric lymph nodes of mice were detected for expressions of all five subtypes of dopamine receptor mRNAs by reverse transcription-polymerase chain reaction. Lymphocyte proliferation and production of interferon-γ (IFN-γ) and interleukin-4 (IL-4) in response to concanavalin A (Con A) were measured by colorimetric methyl-thiazole-tetrazolium assay and cytometric bead array, respectively, after the cells were exposed to dopamine D1-like or D2-like receptor agonists and antagonists. Meanwhile, content of cAMP and phosphorylation of cAMP-response element-binding (CREB) in the lymphocytes were examined by 125I-cAMP radioimmunoassay and Western blot assay, respectively.

RESULTS: T lymphocytes expressed all the five subtypes of dopamine receptor mRNAs, i.e., D1, D2, D3, D4 and D5 receptors. SKF38393, an agonist of dopamine D1-like receptors (D1 and D5 receptors) only reduced the IFN-γ production, but did not significantly affect the proliferative response, IL-4 production, cAMP content or CREB activation of the lymphocytes. The SKF38393-induced decrease in IFN-γ level was blocked by the D1-like receptor antagonist SCH23390. Quinpirole, an agonist of dopamine D2-like receptors (D2, D3 and D4 receptors) attenuated the lymphocyte proliferation to Con A, and decreased the IFN-γ but increased the IL-4 production. Meanwhile, the quinpirole diminished the cAMP content and the phosphorylated CREB level in the lymphocytes. All the quinpirole-induced changes were reversed by dopamine D2-like receptor antagonist haloperidol.

CONCLUSIONS: Five dopamine receptor subtypes of the two families, D1-like and D2-like receptors, exist on T lymphocytes of mice. Of the two families, D2-like receptors are more important in mediating modulation of T cell function than D1-like receptors. D2-like receptors are involved in suppression of T helper 1 (Th1) cell function and enhancement of Th2 cell function through negative link to cAMP-CREB pathway....

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Journal Article 2010; 31(2): 270-274 PubMed PMID: 20424586 Citation  Keywords:  Adult, Blood Glucose:metabolism, Diabetes Complications:blood, Fasting:blood, Female, Hemoglobin A, Glycosylated:metabolism, Humans, Hyperprolactinemia:blood, Magnetic Resonance Imaging, Male, Middle Aged, Pituitary Gland:pathology, Prevalence, Prolactin:.   

OBJECTIVE: Prolactin levels have been shown to be reduced in poorly controlled diabetes mellitus; however, diabetic patients with high prolactin levels may be seen in clinical practice. The aim of this study was to evaluate diabetic patients with hyperprolactinemia, and to determine the role of macroprolactinaemia in these patients.

MATERIALS AND METHODS: The study included 174 patients (153 women and 21 men) with hyperprolactinemia, retrospectively reviewed over a 2 years period. Data on presenting symptoms, the presence of diabetes mellitus, prolactin levels, macroprolactin levels, pituitary magnetic resonance imaging were collected in all patients. In addition; HbA1c, fasting blood glucose levels and postprandial glucose levels were collected in diabetic patients.

RESULTS: Of the 174 patients, 27 were diagnosed with diabetes mellitus (15.5%). Eighteen of the diabetic patients with hyperprolactinaemia had macroprolactinaemia (66.6%). The prevalence of macroprolactinaemia in diabetic patients is higher than the non-diabetic population (66.6% vs. 39.5%, p=0.009). In diabetic patients with macroprolactinaemia, HbA1c levels were higher than the diabetic patients without macroprolactinaemia.

CONCLUSION: The prevalence of macroprolactinaemia in diabetic patients was higher than the non-diabetic population. It seems necessary to determine macroprolactin levels in diabetic patients with hyperprolactinaemia; and in this case, further diagnostic evaluation is not warranted....

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Journal Article 2010; 31(2): 193-197 PubMed PMID: 20424580 Citation  Keywords:  Cell Proliferation, Cells, Cultured, Coculture Techniques, Decidua:cytology, Embryo Implantation:physiology, Female, Humans, Matrix Metalloproteinase 2:secretion, Matrix Metalloproteinase 9:secretion, Placenta:cytology, Pregnancy, Trophoblasts:cytology,.   

OBJECTIVE: Proliferation, migration and invasion of trophoblastic cells into the maternal endometrium are essential steps in human embryo implantation and placentation. Trophoblast invasion is normally limited in time, only during first and early second trimester of pregnancy, and in space, limited to the endometrium and the proximal third of myometrium. This process requires among other factors: the metalloproteinases (MMP) 2 and 9. Shallow trophoblast invasion is associated with pathologies including preeclampsia and fetal growth restriction whereas unlimited invasion is associated with hydatidiform moles and choriocarcinomas.

METHODS: In order to understand the role of decidua in this endometrial invasion by trophoblastic cells, we have developed a model of coculture of decidual and cytotrophoblastic cells in which we can evaluate the effect of each partner on the proliferative and invasive properties of the other.

RESULTS: Surprisingly, decidual cells secrete highest levels of MMPs, and their invasive potential seems to be increased in presence of cytotrophoblast (CTB). In contrast, invasive properties of CTB are not modified by decidual cells.

CONCLUSION: CTB secrete factors that favour invasion whereas decidua seems not to play a major role in regulating CTB invasion in vitro. Moreover, it is interesting to note that decidual cells could have potent invasive capacity which could explain, at least in part, endometriosis....

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Journal Article 2010; 31(1): 67-72 PubMed PMID: 20150874 Citation  Keywords:  Animals, Animals, Genetically Modified, Cell Proliferation:drug effects, Chick Embryo:metabolism, Down-Regulation:drug effects, Embryonic Development:drug effects, Ganglia, Spinal:drug effects, Gene Expression Regulation, Developmental:drug effects, Gene .   

OBJECTIVE: Protein Isl-1 RNA interference and over expression in early chicken embryo dorsal root ganglia (DRG) were used to investigate the function of Isl-1 in DRG cell proliferation.

METHODS: Isl-1 targeted shRNA expression vector and Isl-1 over-expression vector were transfected into chicken embryo DRG by in ovo electroporation. Then, the DRG proliferation rate was detected by BrdU immunohistochemistry.

RESULTS: The rate of DRG cell proliferation increased after Isl-1 knock-down and decreased after Isl-1 over-expression.

CONCLUSIONS: In this study, we found that Isl-1 negatively modulates DRG cell proliferation....

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Journal Article 2009; 30(1): 107-110 PubMed PMID: 19300395 Citation  Keywords:  Acromegaly:etiology, Adenoma:complications, Adrenocorticotropic Hormone:secretion, Adult, Aged, Cell Proliferation:drug effects, Cell Survival:drug effects, Drug Evaluation, Preclinical, Female, Human Growth Hormone:secretion, Humans, Hypoglycemic Agents:.   

OBJECTIVES: Rosiglitazone (RGZ) belongs to thiazolidinediones - new class of antidiabetic drugs which are PPARgamma agonists. It was shown that tumoral tissue, including the pituitary adenomas, posses PPARgamma receptors. The activation of PPARgamma receptors inhibits tumour growth in rodents and induces the oncostatic effect on human cancer cell lines. The aim of the present study was to examine the anti-tumour effect of RGZ on human pituitary adenomas in vitro.

MATERIALS AND METHODS: Cells of eight pituitary adenomas removed neurosurgically were used to our experiment. Before the operation, the hormonal secretion of the tumour was estimated. After the surgery, the histological diagnosis and immunohistochemical detection of pituitary hormones and PPARgamma receptors were performed. The cells of pituitary tumours were exposed in the primary culture to RGZ at the concentrations of 10(-9)-10(-4) M for 24 hours. To measure the cell growth the modified colorimetric Mossman method detecting the cells viability was applied.

RESULTS: On the basis of the pre-operative diagnosis the 6 clinically non-functioning adenomas (CNFPA), one case of acromegaly and one case of Cushing's disease were recognized. In 5 out of 6 CNFPA the immunopositive reaction for different pituitary hormones such as: LH, HGH, PRL, FSH and alpha-subunit was detected. Expression of PPARgamma was found in all examined tumours. Rosiglitazone decreased the cell viability of all CNFPA and corticotropinoma for 20% or more. In somatotropinoma inhibition of the cell growth was about 13%. There is no correlation between PPARgamma expression and efficacy of rosiglitazone. THE MAIN FINDING: The obtained results indicate that RZG exerts a suppressive effect on the cell viability in non-functioning pituitary adenomas. The lack of correlation between PPARgamma expression and anti-tumoral effect of RZG suggests that the above-mentioned action of this compound is independent on PPARgamma expression.

CONCLUSION: Our data suggest that rosiglitazone may be useful in the treatment of non-functioning pituitary adenomas, but its efficacy in Cushing's disease and acromegaly requires further study....

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