Hyperprolactinemia and immunohistochemical expression of intracellular prolactin and prolactin receptor in primary central nervous system tumors and their relationship with cellular replication

The role of prolactin (PRL) in the CNS remains uncertain. We evaluated the presence of hyperprolactinemia, intracellular prolactin (ICP), and prolactin receptor (PRL-R) in primary CNS tumors, and their relationship with cellular replication with a prospective cross-sectional study of 82 consecutive patients with primary CNS tumors admitted for neurosurgical resection between October 2003 and September 2005. Patients submitted to a questionnaire, and venous blood samples were obtained for measurement of serum PRL and TSH. Immunohistochemical analyses were performed to evaluate the presence of ICP, PRL-R, and Ki-67. Serum PRL levels ranged from 2 to 70 ng/ml, and hyperprolactinemia was detected in 25 cases (30.5%). ICP was detected in 18 patients (21.9%), in whom PRL ranged from 2 to 32 ng/ml. A positive correlation was found between PRL levels and the presence of ICP (Student's t test, P = 0.022). The PRL-R was observed immunohistochemically in 32 cases (39%). The frequencies of hyperprolactinemia, ICP, and PRL-R were similar across the several histological types of CNS tumors. Ki-67 index was similar in all groups. Hyperprolactinemia and intracellular presence of PRL and PRL-R were common findings in this population, suggesting a role for PRL in CNS tumor genesis.     

Physical activity and inactivity in relation to sex hormone,prolactin, and insulin-like growth factor concentrations in premenopausal women

An association between physical activity and premenopausal breast cancer risk may be due, in part, to relationships with sex hormones or growth factors. Therefore, we assessed whether MET-h/week of total physical activity (moderate-to-vigorous intensity), walking, or vigorous physical activity, and h/week of standing or sitting were associated with plasma concentrations of several hormones. We examined levels of estrogens, androgens, progesterone, prolactin, sex hormone binding globulin (SHBG), insulin-like growth factor-1 (IGF-1), IGF binding protein-3, and growth hormone (GH) in 565 premenopausal women, ages 33–52 years, from the Nurses’ Health Study II (NHSII). About 87% of women had both timed follicular and luteal samples; other women had one untimed sample. In general we observed few associations between sex hormone or IGF levels and measures of physical activity or inactivity. However, free testosterone was modestly inversely associated with total physical activity (p-trend = 0.02). Luteal estradiol, free estradiol, and estrone also were inversely associated with total physical activity (p-trend = 0.10, 0.04, 0.01, respectively); however, the trend was substantially attenuated when excluding women with anovulatory cycles or irregular cycles. These cross-sectional results suggest that physical activity and inactivity have limited associations with premenopausal sex hormone and growth factor levels, except possibly luteal estrogens. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. Support for this project was from NIH grants CA67262, CA50385, P50 CA089393, and DAMD-17-02-1-0692. Dr. Eliassen was supported by Cancer Education and Career Development Grant R25 CA 098566-2 from the National Cancer Institute.     

Are sexual side effects of prolactin-raising antipsychotics reducible to serum prolactin?

OBJECTIVE: To assess the degree to which sexual side effects (SSE) are associated with prolactin-raising antipsychotics, and to what degree such SSE are reducible to serum prolactin levels. METHOD: A large sample (n=264) of patients treated for 6 weeks with prolactin-raising and prolactin-sparing antipsychotics was assessed for changes in sexual performance in terms of libido, arousal and orgasm using the Antipsychotics and Sexual Functioning Questionnaire. For men also erection and ejaculation were evaluated. At 6 weeks, prolactin levels were assessed and analyzed in relation to sexual performance. RESULTS: Men and women reported SSE (libido and orgasm) with about the same frequency. Prolactin-raising medication induced significantly more SSE than prolactin-sparing medication (adjusted OR=3.4, 95% CI: 1.8, 6.5) with 43% of emerging SSE attributable to prolactin-raising medication. When adjusted for serum prolactin, the association between prolactin-raising medication and SSE was reduced but remained significant (OR=2.1, 95% CI: 1.0, 4.5); 27% of emerging SSE remained attributable to prolactin-raising medication. For erectile and ejaculatory dysfunction in men, the attributable fraction due to prolactin-raising medication was 32% before, and 11% after adjustment for serum prolactin. CONCLUSIONS: Around 40% of emerging SSE in schizophrenia are attributable to the prolactin-raising properties of antipsychotic medication. Of this attributable fraction, around one-third to two-thirds is directly reducible to the effects of serum prolactin.     

Relationship between prolactin secretion, and plasma risperidone and 9-hydroxyrisperidone concentrations in adolescents with schizophreniform disorder

BACKGROUND: Treatment with the atypical antipsychotic risperidone can result in elevated prolactin levels. To date, the relationships between plasma concentrations of prolactin, risperidone and its active 9-hydroxy-metabolite have been little investigated in adolescents with psychosis. METHODS: Prolactin levels were determined at baseline in 16 hospitalized drug-na?ve adolescents meeting DSM-IV criteria for schizophreniform disorder. Prolactin, risperidone, 9-hydroxyrisperidone levels were subsequently determined after 3 weeks of oral risperidone treatment. RESULTS: Compared with pretreatment values, prolactin levels at endpoint were significantly increased (p<0.00001) and correlated with risperidone doses (r=0.58, N=16, p<0.02), and plasma levels of risperidone (r=0.60, N=16, p<0.02) and 9-hydroxyrisperidone (r=0.54, N=16, p=0.03). CONCLUSIONS: These data suggest that risperidone's effect on prolactin release is dose-dependent in adolescents and is linked to both plasma risperidone and 9-hydroxyrisperidone concentrations.     

Hypersensitivity of 5-HT2 receptors in OCD patients. An increased prolactin response after a challenge with meta-chlorophenylpiperazine and pre-treatment with ritanserin and placebo

INTRODUCTION: Several studies in obsessive compulsive disorder (OCD) have provided circumstantial evidence that the 5-HT-system is involved in the pathophysiology of OCD. To further examine the role of 5-HT receptors we studied the behavioural and neuroendocrine effects of different doses of meta-chlorophenylpiperazine (mCPP) in OCD patients and healthy controls, after pre-treatment with ritanserin, a 5-HT2 receptor antagonist, and placebo. DESIGN: Twenty patients and 20 healthy controls received 0.1, 0.3 or 0.5 mg/kg mCPP or placebo orally. Each subject was tested two times, receiving both times the same dosage of mCPP or placebo with ritanserin or placebo pre-treatment. All was done under double-blind conditions. OC-symptoms and hormone levels were measured. RESULTS: The increase in prolactin level after mCPP administration was more robust in patients than in controls. The prolactin response following 0.5 mg/kg of mCPP was partially blocked by ritanserin in patients, but totally blocked in healthy controls. The cortisol responses in both groups did not differ statistically significant from each other and were entirely blocked by ritanserin. None of the subjects experienced an exacerbation of obsessive compulsive symptoms. CONCLUSION: The neuroendocrine results show an enhanced susceptibility of OCD patients for the mCPP-induced prolactin response, which effect seems to be due to an increased sensitivity of 5-HT2 receptors.     

A prospective analysis of testicular androgenic function in recipients of a renal allograft

Eighteen adult males with end stage renal disease (ESRD) were studied to determine the serum levels of gonadotropins (LH and FSH), prolactin (PRL) and testosterone. All of the patients were studied longitudinally while undergoing maintenance hemodialysis (HD) and six months after renal transplantation. Prior to transplantation, significantly high levels of gonadotropins and PRL were observed. During HD the serum testosterone levels tended to be subnormal in most of the uremic patients and low normal in some of the subjects. Renal transplantation led to a significant improvement (P < 0.05) in serum testosterone. Elevated gonadotropin and PRL levels observed in patients on HD returned to the normal range in most of the patients after successful renal transplantation.     

Abnormal ACTH and prolactin responses to fenfluramine in rats exposed to single and multiple doses of MDMA

The present study examined the persistent functional consequences associated with exposure to single and multiple doses of (±) 3,4-methylenedioxymethamphetamine (MDMA) as reflected by the neuroendocrine responses to d,l-fenfluramine (FEN). Adult male rats were administered a single dose of MDMA (20 mg/kg, SC) and challenged 2 weeks later with saline or FEN (2, 4, 6 and 8 mg/kg, SC). The corticotropin (ACTH) response to FEN (6 and 8 mg/kg) was blunted and the prolactin response to FEN (4 and 6 mg/kg) was enhanced in MDMA pre-treated rats. The ACTH and prolactin responses to FEN (6 mg/kg, SC) were then evaluated 4, 8 and 12 months after exposure to single and multiple doses MDMA (20 mg/kg, SC and 20 mg/kg, SC, bid, × 4 days, respectively). The ACTH response to FEN was significantly reduced at 4 and 8 months in both MDMA treatment groups, and at 12 months in the multiple dose group only. In contrast, the prolactin response to FEN was enhanced in both groups of MDMA treated rats at 4 months, but only in the multiple dose group at 8 months. By 12 months, the prolactin response to FEN had normalized. Following multiple doses of MDMA, 5-HT concentrations were reduced significantly in the frontal cortex at 4 and 12 months. The results indicate that exposure to single or multiple doses of MDMA can produce functional alterations which can persist for months, whereas the biochemical sequelae were less robust and shorter lived. Received: 12 November 1996/Final version: 14 January 1997     

热惊厥幼龄大鼠脑内Prolactin蛋白及Zinc transporter 1 mRNA表达

目的 探讨热应激(Heat stress,HS)和热惊厥(Febrile convulsions,FC)对脑内催乳素蛋白(Prolactin,PRL)和锌离子转运体1(Zinc transporter 1,ZnT1)表达的影响,探讨FC的神经免疫学机制.方法 实验在浙江大学附属邵逸夫医院中心实验室进行.采用热水浴诱导FC模型.21 d龄雄性sD大鼠随机分为正常对照组(8只)和热应激组(28只),28只热应激处理大鼠中15只达到5级(设为热性惊厥组,FC),10只未出现惊厥(设为单纯热应激组,HS),3只达到2级惊厥,弃用.应用免疫组织化学技术对HS和FC大鼠PRL免疫反应性在不同脑区的表达进行分析,原位杂交检测ZnT1表达.各组阳性细胞数采用方差分析进行统计.结果 ①对照组大脑皮层偶见零星表达,着色淡且无定位分布特征.HS组PRL-IR阳性细胞在大脑皮层PIR、Ent和Rs区免疫染色较深,PRH、PAR和Fr区染色较浅;另外PRL-IR阳性细胞还分布于丘脑中线一带;而FC组则于大脑皮层、海马、杏仁核、丘脑及下丘脑见大量PRL-IR阳性细胞,呈弥漫性分布,无明显核团分布特征.②HS和FC两组大脑皮层各区PRL-IR阳性细胞数均明显高于对照组(P<0.01).FC组大鼠大脑皮层PIR、Ent、RS区PRL-1R阳性细胞数与HS组大鼠差异无统计学意义(F值分别为688.9、744.3、0.56,P>0.05),PRH和PAR区FC组明显高于HS组(F值分别为2.68、1.48,P<0.01).③FC组海马区域可见明显ZnT1 mRNA表达,而HS组和对照组无明显表达.结论 ①PfuL在HS组和FC组大脑皮层各区明显表达,而FC组在海马和杏仁核等前脑结构内亦有明显表达,表明PRL不仅与热应激的中枢调控有关,也参与海马等前脑结构对惊厥活动的中枢调控机制.②FC组海马ZnT1 mRNA明显表达提示FC组海马区域存在异常增高的锌离子转运.     

Prolactin inhibits the activity of tyrosine hydroxylase in cultured bovine adrenal chromaffin cells in a dose-dependent manner

Prolactin can modulate the adrenal medulla function, but it has not yet been established whether its action is directly exerted on the adrenal medulla cells. In this work, we have studied the effect of several concentrations of prolactin on the synthesis, storage and release of norepinephrine and epinephrine using cultured bovine adrenal chromaffin cells. In these cells, prolactin inhibited the activity of tyrosine hydroxylase, the rate-limiting enzyme in the catecholamine synthesis, in a dose-dependent manner, from a concentration above 50 ng/ml of prolactin in the incubation medium. Surprisingly, this dose-dependent decrease was not accompanied by changes in the catecholamine release, since the secretion of both norepinephrine and epinephrine as well as the total catecholamine secretion were not significantly altered by the different prolactin concentrations. Moreover, the cellular content of both catecholamines was not altered by prolactin. In summary, these observations allow us to conclude that prolactin exerts a direct inhibitory effect on the tyrosine hydroxylase activity in cultured adrenal chromaffin cells without altering catecholamine release.     

原发性癫痫患者神经内分泌免疫网络调节功能变化及其临床意义

检测原发性癫痫患者和对照组血和脑脊液(CSF)中6种神经肽,血中5项免疫指标和催乳素(PRL)的含量,对三者之间的关系进行相关分析。结果显示,与对照组相比,癫痫组(1)血中亮氨酸脑啡肽(LEK)、强啡肽(Dyn)、精氨酸加压素(AVP)、神经降压素(NT)、生长抑素(SS)和PRL以及CSF中的LEK、AVP、NT和SS含量均显著增高;(2)血中NK细胞、ADCC、T淋巴细胞总花环形成率(TRF)、T淋巴细胞活性花环形成率(ARF)和总补体(CH50)含量均显著降低;(3)在神经肽、免疫指标和PRL三者中,有多项指标之间存在显著相关性。结果提示,神经内分泌免疫网络调节功能变化在原发性癫痫的发病机理中可能有一定地位。