Hyperprolactinemia associated with psychiatric disorders / Hiperprolactinemia asociada con trastornos psiquiátricos

Abstract Hyperprolactinemia may be associated with psychiatric disorders in the context of two scenarios: antipsychotic-induced hyperprolactinemia and psychiatric disorders arising from the medical treatment of hyperprolactinemia. Both situations are particularly common in psychiatric and endocrine clinical practice, albeit generally underestimated or unrecognized. The aim of this article is to provide tools for the diagnosis and treatment of hyperprolactinemia associated with psychiatric disorders to raise awareness, especially among psychiatrists and endocrinologists, so that these professionals can jointly focus on the appropriate management of this clinical entity.

Resumen La hiperprolactinemia puede asociarse con trastornos psiquiátricos en el contexto de dos escenarios: la hiperprolactinemia inducida por antipsicóticos y trastornos psiquiátricos surgidos por el tratamiento médico de la hiperprolactinemia. Ambas situaciones son particularmente comunes en la práctica clínica psiquiátrica y endocrinológica, aunque generalmente subestimadas o inadvertidas. El objetivo de este artículo es proporcionar herramientas de diagnóstico y tratamiento de la hiperprolactinemia asociada a trastornos psiquiátricos, para concientizar particularmente a psiquiatras y endocrinólogos a enfocar en conjunto el manejo apropiado de esta entidad.

Adenoma hipofisario ectópico del seno esfenoidal persistente tras cirugía manejado con tratamiento conservador / Ectopic pituitary adenoma in the sphenoid sinus persistent after surgery managed with conservative treatment

Los adenomas hipofisarios ectópicos (EPA) constituyen un reto diagnóstico, dada su escasa prevalencia y variada presentación en la que puede incluirse un síndrome de hipersecreción de hormonas hipofisarias. La clínica suele ser larvada e inespecífica, no presentan ninguna característica radiológica diferencial y el diagnóstico habitualmente es anatomopatológico. Sin embargo, a pesar de ser tumores benignos, pueden presentar un comportamiento agresivo, con invasión ósea y difícil resección completa, por lo que un diagnóstico de sospecha precoz podría resultar en un tratamiento más eficaz y con un menor número de complicaciones. Presentamos el caso de una paciente con un adenoma hipofisario ectópico silente en el seno esfenoidal con inmunohistoquímica positiva para Hormona de crecimiento (GH) y prolactina que presentaba restos tumorales tras la intervención quirúrgica y ha sido manejada con tratamiento médico conservado, con buenos resultados.

Ectopic pituitary adenomas constitute a diagnostic challenge, given their low prevalence and varied presentation in which a pituitary hormone hypersecretion syndrome may be included. Clinical symptoms are usually latent and nonspecific, they have no differential radiological characteristics and the diagnosis is usually anatomopathological. However, despite being benign tumors, they can exhibit aggressive behavior, with bone invasion and difficult complete resection, so a diagnosis of early suspicion could result in more effective treatment and fewer complications. We present the case of a patient with a silent ectopic pituitary adenoma in the sphenoid sinus with positive immunohistochemistry for Growth Hormone (GH) and prolactin who had tumor remnants after surgery and was managed with conservative medical treatment, with good results.

Interactions between prolactin and kisspeptin to control reproduction

ABSTRACT Prolactin is best known for its effects of stimulating mammary gland development and lactogenesis. However, prolactin is a pleiotropic hormone that is able to affect several physiological functions, including fertility. Prolactin receptors (PRLRs) are widely expressed in several tissues, including several brain regions and reproductive tract organs. Upon activation, PRLRs may exert prolactin’s functions through several signaling pathways, although the recruitment of the signal transducer and activator of transcription 5 causes most of the known effects of prolactin. Pathological hyperprolactinemia is mainly due to the presence of a prolactinoma or pharmacological effects induced by drugs that interact with the dopamine system. Notably, hyperprolactinemia is a frequent cause of reproductive dysfunction and may lead to infertility in males and females. Recently, several studies have indicated that prolactin may modulate the reproductive axis by acting on specific populations of hypothalamic neurons that express the Kiss1 gene. The Kiss1 gene encodes neuropeptides known as kisspeptins, which are powerful activators of gonadotropin-releasing hormone neurons. In the present review, we will summarize the current knowledge about prolactin’s actions on reproduction. Among other aspects, we will discuss whether the interaction between prolactin and the Kiss1-expressing neurons can affect reproduction and how kisspeptins may become a novel therapeutic approach to treat prolactin-induced infertility.

Methylmercury inhibits prolactin release in a cell line of pituitary origin

Heavy metals, such as methylmercury, are key environmental pollutants that easily reach human beings by bioaccumulation through the food chain. Several reports have demonstrated that endocrine organs, and especially the pituitary gland, are potential targets for mercury accumulation; however, the effects on the regulation of hormonal release are unclear. It has been suggested that serum prolactin could represent a biomarker of heavy metal exposure. The aim of this study was to evaluate the effect of methylmercury on prolactin release and the role of the nitrergic system using prolactin secretory cells (the mammosomatotroph cell line, GH3B6). Exposure to methylmercury (0-100 μM) was cytotoxic in a time- and concentration-dependent manner, with an LC50 higher than described for cells of neuronal origin, suggesting GH3B6 cells have a relative resistance. Methylmercury (at exposures as low as 1 μM for 2 h) also decreased prolactin release. Interestingly, inhibition of nitric oxide synthase by N-nitro-L-arginine completely prevented the decrease in prolactin release without acute neurotoxic effects of methylmercury. These data indicate that the decrease in prolactin production occurs via activation of the nitrergic system and is an early effect of methylmercury in cells of pituitary origin.

Effects of melatonin and prolactin in reproduction: review of literature / Efeitos da melatonina e da prolactina na reprodução: revisão de literatura.

Summary The pineal gland is responsible for producing a hormone called melatonin (MEL), and is accepted as the gland that regulates reproduction in mammals. Prolactin (PRL) also exhibits reproductive activity in animals in response to photoperiod. It is known that the concentrations of PRL are high in the summer and reduced during winter, the opposite of what is seen with melatonin in these seasons. In placental mammals, both prolactin and melatonin affect implantation, which is considered a critical point of pregnancy, since a successful pregnancy requires the development of a synchronous interaction between the endometrium and blastocyst for placental development. It is also known that PRL levels during pregnancy are essential for the maintenance of pregnancy, because this hormone induces the corpus luteum to produce progesterone, in addition to stimulating blastocyst implantation to maintain pregnancy and form the placenta. However, melatonin levels in plasma have also been shown to increase during pregnancy, peaking at the end of this period, which suggests that this hormone plays an important role in the maintenance of pregnancy. Thus, it is clear that treatment with prolactin or melatonin interferes with the processes responsible for the development and maintenance of pregnancy.

Resumo A glândula pineal é responsável pela produção do hormônio melatonina (MEL), sendo aceita como a glândula reguladora da reprodução em mamíferos. A prolactina (PRL) também exibe atividade reprodutiva em animais, em resposta ao fotoperíodo. Sabe-se que as concentrações de PRL são elevadas durante o verão e baixam durante o inverno, ocorrendo o oposto com os níveis do hormônio melatonina nessas estações. Nos mamíferos placentários, tanto a melatonina quanto a prolactina influenciam a implantação, que é considerada o ponto crítico da gravidez, pois o sucesso da gestação requer o desenvolvimento de uma interação sincronizada entre o endométrio e o blastocisto para o desenvolvimento da placenta. Sabe- -se ainda que os níveis de PRL durante a gestação são essenciais para a manutenção da gravidez, pois esse hormônio induz o corpo lúteo a produzir progesterona, além de estimular a implantação do blastocisto, mantendo a prenhez e o desenvolvimento placentário. Em contrapartida, tem-se demonstrado também que os níveis de melatonina no plasma aumentam durante a gestação, atingindo valores elevados no fim desse período, sugerindo que esse hormônio desempenhe um importante papel na manutenção da gestação. Dessa forma, fica claro que o tratamento com prolactina ou melatonina interfere nos processos responsáveis pelo desenvolvimento e pela manutenção da gestação.

Clinicopathologic Analysis of Pituitary Adenoma: A Single Institute Experience

Pituitary adenoma (PA) is a common benign neuroendocrine tumor; however, the incidence and proportion of hormone-producing PAs in Korean patients remain unknown. Authors analyzed 506 surgically resected and pathologically proven pituitary lesions of the Seoul National University Hospital from 2006 to 2011. The lesions were categorized as: PAs (n = 422, 83.4%), Rathke's cleft cysts (RCCs) (n = 54, 10.6%), inflammatory lesions (n = 8, 1.6%), meningiomas (n = 4), craniopharyngiomas (n = 4), granular cell tumors (n = 1), metastatic renal cell carcinomas (n = 2), germinomas (n = 1), ependymomas (n = 1), and unsatisfactory specimens (n = 9, 1.8%). PAs were slightly more prevalent in women (M: F = 1:1.17) with a mean age of 48.8 yr (9-80 yr). Immunohistochemical analysis revealed that prolactin-producing PAs (16.6%) and growth hormone-producing adenomas (9.2%) were the most common functional PAs. Plurihormonal PAs and nonfunctioning (null cell) adenomas were found in 14.9% and 42.4% of patients with PAs, respectively. The recurrence rate of PAs was 11.1%, but nearly 0% for the remaining benign lesions such as RCCs. 25.4% of patients with PAs were treated by gamma-knife after surgery due to residual tumors or regrowth of residual tumor. In conclusion, the pituitary lesions and the proportions of hormone-producing PAs in Korean patients are similar to those of previous reports except nonfunctioning (null cell) PAs, which are unusually frequent.

Comparison of Serum Prolactin Level between I.V. Ranitidne and I.V Cimetidine Administration in Albino Rabbits and Possible Role of Histamine 1 and 2 Receptors in Prolactin Secretion.

The serum prolactin levels of eighteen normal rabbits are measured by using method of RIA. The values before drug treatment are taken as the control values of each group. Prolactin levels after 15, 30 and 45 minutes of i.v. Ranitidine treated group, when compared to its own control values, are not significantly raised whereas those levels after i.v. cimetidine are raised significantly in the paired t-test. Prolactin levels of i.v.cimetidine group , when compared with iv ranitidine group by unpaired t-test, are significantly raised [t = 2.737, 4.215 and 2.834 at 10,15, 45 minutes intervals respectively, at 10 degree of freedom, (p < 0.05)]. In the comparison between i.v. cimetidine and i.v. cimetidine pretreated with i.v. diphenhydramine groups (by unpaired t- test), presence of diphenhydramine HCl can cause statistically significant reduction at 30,45 minutes (at 10 degree of freedom. t- 2.666 and 2.440 respectively, (p < 0.05). The result shows that i.v.cimetidine can significantly liberate prolactin from the Ant. Pituitary, unlike i.v. ranitidine. Central H1 and H2 receptors contribute in prolactin secretion.

Structurally conserved C-RFa revealed prolactin releasing activity in vitro and gene expression changes in pituitary of seasonally acclimatized carp

Here we show the cloning and characterization of a novel homolog of prepro C-RFa cDNA from Cyprinus carpió. The deduced preprohormone precursor of 115 amino acids leads to a mature bioactive peptide of 20 amino acids with identical sequence to other teleost C-RFa. Modeling of the mature C-RFa peptide highlighted significant similarity to homologous human PrRP20, specifically the conserved amphipathic system defined by the C-terminal alpha-helix. Clearly, the synthetic C-RFa peptide stimulated prolactin release from primary cultured fish pituitary cells. For the first time, significant variation was shown in C-RFa mRNA and protein levels in the hypothalamus and pituitary between summer- and winter-acclimatized carp. Furthermore, C-RFa protein distribution in carp central nervous tissue was visualized by immunodetection in fibers and cells in hypothalamus, olfactory tract, cerebellum and pituitary stalk. In conclusion, we demonstrated the structure conservation of C-RFa in teleosts and mammals and immunopositive cells and fibers for C-RFa in brain areas. Finally, the increase of C-RFa expression suggests the participation of this hypothalamic factor in the mechanism of modulation in PRL expression in carp.

Mecanismos das alterações do desempenho físico na programação pelo bloqueio da prolactina ao final da lactação / Mechanisms of changes in physical performance in the programming by the blockage of prolactin at the end of lactation

Anteriormente, observamos que o uso de bromocriptina (BRO), um agonista dopaminérgico inibidor de prolactina, ao final da lactação, leva ao bloqueio da produção de leite, causando uma desnutrição moderada da prole e programando uma maior massa corporal total (MCT) e de gordura visceral (MGV) e hipofunção tireóidea na idade adulta, características que são deletérias para o adequado desempenho físico. Sendo assim, avaliamos nestes animais alguns dos mecanismos relacionados à capacidade física como o conteúdo de glicogênio (muscular e hepático), as concentrações séricas de insulina, hormônios tireóideos (HTs), a atividade da enzima glicerol-fosfato desidrogenase mitocondrial (GPDm), que é regulada por HTs, no fígado, no TAM e no músculo esquelético. Indicadores de estresse oxidativo também foram avaliados utilizando o teste de espécies reativas ao ácido tiobarbitúrico (TBARs) e capacidade antioxidante total (CAT), na prole adulta aos 90 e 180 dias de idade cujas mães receberam BRO (1 mg/dia) nos 3 dias finais da lactação. O desempenho físico foi avaliado aos 90 e 180 dias de idade pela quantificação do tempo máximo de nado (TMN) em metade dos animais de cada grupo (n=10). Os ratos foram colocados em piscina com temperatura controlada (32+-2ºC) com carga adicional presa à cauda (equivalente a 5% da MCT). Aos 90 dias a MGV foi maior no grupo BRO (+56%), enquanto que os valores de glicemia (-10%) e atividade da GPDm no músculo (-53%) e n TAM (-40%) foram menores. O conteúdo de glicogênio no músculo sóleo não apresentou diferenças em resposta ao tratamento experimental ou exercício em ambas as idades, enquanto que no EDL nós observamos uma mobilização de glicogênio nos aminais exercitados de forma similar. Os animais do grupo BRO apresentaram um maior TMN (+35%), com menor produção de lactato pós-exercício (-20%). O maior conteúdo de glicogênio hepático observado no grupo BRO aos 90 dias na condição basal (+53%), e sua maior degradação com o exercício (-57%)...

Previously, we observed that the utilization of bromocriptine (BRO) a dopaminergic agonist that inhibits prolactin, at the end of lactation causes milk production blockade, provoking a moderate malnutrition in the pups and programming a higher body mass and visceral fat mass (VFM) and thyroid hypofunction in adult age, which are deleterious conditions for adequate physical performance. Therefore, we evaluated some mechanisms related to physical performance like blood lactate, glycemia and glycogen content (muscle and liver), serum insulin and thyroid hormones (THs) concentrations, mitochondrial glycerol-phosphate dehydrogenase activity (mGPD), and enzyme regulated by thyroid hormones (THs) in liver, brown adipose tissue (BAT) and skeletal muscle. Oxidative stress indicators were also evaluated using thiobarbituric acid reactive substances (TBARs) and total antioxidant capacity (TAC) in adult pups (90 and 180 days old), whose mothers received BRO (1mg/day) at the last 3 days of lactation. Physical performance was evaluated on 90 and 180 days old animals (n=10). The rats were placed in a swimming pool with controlled temperature (89+-2ºF) with additional load attached to the tail equivalent to 5% of body mass (BM). VFM was higher in 90 days old BRO group (+56%), while glycemia (-10%) and mGPD activity in muscle (-53%) and BAT (-40%) were lower. Glycogen content in soleous muscle did not present differences in response to experimental treatment or exercise in both ages, while in EDL we observed glycogen mobilization with exercise in a similar way. BRO animals presented higher MST values (+35%), with lower post-exercise lactate production (-20%). The higher hepatic glycogen content observed in BRO group at 90 days old in the basal period (+53%), and its higher degradation (-57%) together with the higher activity of mGPD in muscle in exercised animals (+172%) could contribute to the better physical performance in that age. Additionally, the higher values...

Hiperprolactinemia en niños y adolescentes, conceptos e interrogantes actuales / Hyperprolactinemia in children and adolescents, current questions and concepts

La hiperprolactinemia constituye la alteración endocrina más común del eje hipotálamo-hipofisario, aunque su prevalencia en la población infantojuvenil no está aún claramente definida. Además de la Prolactina (PRL) nativa (23Kda), se han descripto numerosas variantes moleculares (PRL glicosilada, fosforilada, sulfatada, deaminada, BIG PRL, BIG BIG PRL, etc.), algunas de ellas con menor o ausente actividad biológica. El recién nacido presenta inmadurez fisiológica del eje prolactínico, alcanzando niveles de hasta 800 ng/mL en las primeras horas de vida. Posteriormente, cualquier proceso que interrumpa la secreción de dopamina, interfiera con su liberación hacia los vasos portales hipofisarios o bloquee los receptores dopaminérgicos de las células lactotróficas, puede causar hiperprolactinemia. La patología tumoral constituye el diagnóstico de mayor relevancia. Los prolactinomas poco frecuentes tienen, por su presentación clínica en niños y adolescentes, algunas características destacables. De acuerdo a nuestra experiencia, el retraso puberal puede observarse en aproximadamente el 50 % de las pacientes de sexo femenino y en más del 25 % de los varones. La mayor prevalencia de macroadenomas en varones coincide con los hallazgos en adultos y no dependería de un mayor retraso en el diagnóstico. En pacientes con hiperprolactinemia asintomática debe evaluarse la presencia de proporciones alteradas de isoformas de PRL. La cromatografía en columna con sephadex G100, la precipitación con suspensión de proteína A o con PEG y la ultracentrifugación constituyen los métodos más frecuentemente empleados para la detección de las distintas isoformas de PRL. En nuestra experiencia la B PRL constituyó el 6,6 - 32,6 % de la PRL total y la BB PRL constituyó el 40 y el 72 % de la misma en este grupo de pacientes. Por su efectividad y tolerancia, los agonistas dopaminérgicos constituyen la terapia inicial de elección en pacientes en edad pediátrica. La bromocriptina y la cabergolina han sido empleadas y con resultados similares a los de los pacientes adultos. La adquisición de nuevos conceptos y la mejor comprensión de la fisiología y la fisiopatología de los estados hiperprolactinémicos en niños y adolescentes, han modificado las alternativas diagnósticas y terapéuticas

Hyperprolactinemia is the most common endocrine alteration of the pituitary-hypothalamic axis, although its prevalence in the pediatric and adolescent population is not clearly defined yet. Apart from native (23Kda) Prolactin (PRL), many molecular variants (glycosylated, phosphorilated, sulphated, deaminated PRL, BIG PRL, BIG BIG PRL, etc) have been described, some of them with less or no biological activity. Newborns have physiological immaturity of the prolactin axis, attaining levels of as much as 800 ng/mL during the first hours after birth. Subsequently, any process that discontinues dopamine secretion, interferes with its secretion to the pituitary portal vessels or blocks dopaminergic receptors of lactotrophic cells, may cause hyperprolactinemia. Tumor disease is the major diagnosis. Prolactinomas, though rare, have some noticeable features, given their clinical presentation in children and adolescents. Based on our experience, pubertal delay occurs in approximately 50 % of females and in over 25 % of males. The larger prevalence of macroadenomas in males is consistent with findings in adults and would not be related to a later diagnosis. In patients with asymptomatic hyperprolactinemia, the presence of altered proportions of PRL isoforms should be evaluated. G100 Sephadex column chromatography, precipitation with a protein A suspension or PEG and ultracentrifugation, are the most common methods for detection of PRL isoforms. In our experience, B PRL accounted for 6.6 - 32.6 % of total PRL and BB PRL accounted for 40 to 72 % of total PRL in this group of patients. Because of their effectiveness and tolerance, dopaminergic agonists are the initial therapy of choice in pediatric age patients. Bromocriptine and cabergoline have been used with similar results to those obtained in adults. The new concepts gained and the better insight into the physiology and pathophysiology of hyperprolactinemic conditions in children and adolescents have brought about a change in diagnostic and therapeutic alternatives

Ansiedade, pânico e o eixo hipotálamo-pituitária-adrenal / Anxiety, panic and the hypothalamic-pituitary-adrenal axis

OBJETIVO: Este artigo discute a ativação diferencial do eixo hipotálamo-pituitária-adrenal no transtorno de ansiedade generalizada e no transtorno de pânico. MÉTODO: Resultados de recentes revisões da literatura são resumidos e discutidos. RESULTADOS: Os resultados de estudos experimentais que dosaram o hormônio adrenocorticotrópico, o cortisol e a prolactina mostram que ataques de pânico naturais, bem como os provocados por agentes panicogênicos seletivos - como lactato de sódio e dióxido de carbono -, não ativam o eixo hipotálamo-pituitária-adrenal. Agonistas do receptor de colecistocinina do tipo B, como o peptídeo colecistocinina-4 e a pentagastrina, elevam os hormônios de estresse, independentemente da ocorrência de um ataque de pânico, parecendo ativar diretamente o eixo hipotálamo-pituitária-adrenal. O antagonista benzodiazepínico flumazenil não eleva o nível dos hormônios de estresse; porém, este agente farmacológico não induz ataques de pânico de modo consistente. Agentes farmacológicos que aumentam a ansiedade em pacientes de pânico (cafeína, ioimbina, agonistas serotonérgicos), assim como em pessoas saudáveis, elevam o nível dos hormônios de estresse. CONCLUSÕES: Além das diferenças na sintomatologia e na resposta farmacológica, o transtorno de ansiedade generalizada e o transtorno de pânico afetam os hormônios de estresse de modo distinto. Enquanto a ansiedade antecipatória e o transtorno de ansiedade generalizada ativam tanto o eixo hipotálamo-pituitária-adrenal como o simpático-adrenal, o ataque de pânico causa acentuada ativação simpática; porém, afeta pouco o eixo hipotálamo-pituitária-adrenal.

OBJECTIVE: This article focuses on the differential activation of the hypothalamic-pituitary-adrenal axis in generalized anxiety disorder and panic disorder. METHOD: The results of recently reported reviews of the literature are summarized and discussed. RESULTS: The results of experimental studies that assayed adrenocorticotropic hormone, cortisol and prolactin show that real-life panic attacks, as well as those induced by selective panicogenic agents such as lactate and carbon dioxide, do not activate the hypothalamic-pituitary-adrenal axis. Agonists of the cholecystokinin receptor B such as the cholecystokinin-4 peptide and pentagastrin increase stress hormones regardless of the occurrence of a panic attack and, thus, seem to activate the hypothalamic-pituitary-adrenal axis directly. The benzodiazepine antagonist flumazenil does not increase stress hormones, but this agent does not reliably induce panic attacks. Pharmacological agents that increase anxiety in both normal people and panic patients (caffeine, yohimbine, serotonergic agonists) raise stress hormone levels. CONCLUSIONS: In addition to the differences in symptomatology and pharmacological response, generalized anxiety disorder and panic disorder affect stress hormones in distinct ways. While anticipatory anxiety and generalized anxiety disorder activate both the hypothalamic-pituitary-adrenal and the sympathoadrenal axes, panic attack causes major sympathetic activation, but has little effect on the hypothalamic-pituitary-adrenal axis.

Observations on the ultrastructure of a rat mammary gland treated with harmal and borage

It had been indentified by histological, histochemical and morphometrical studies that peganum harmala is a mammogenic herb and borage officinalis is a lactogenic one. To complete our investigation about these two herbs, we performed electron microscopical study. Rats were grouped according to their physiological status into three groups. Each group was subdivided into three subgroups: one control and two experimental. The two experimental groups were treated daily; the 1[st] one with an aqueous extract of peganum harmala seeds and the 2[nd] with an aqueous extract of borage officinalis flowers. After two weeks of treatment, mammary glands were employed for electron microscopical study. In virgin rats, the epithelial and myoepithelial cells were partially differentiated when harmal was given and completely differentiated when borage was given. In pregnant rats, harmal and borage optimize mammary parenchymal growth and induce lactation when these herbs were given. In lactating rats, these herbs exhibited a picture similar to control lactating group but the budding of lipid droplets and the swelling of secretary vesicles were markedly increased. Both harmal and borage stimulate the release of prolactin and induce galactogenesis during pregnancy and promote it during lactation

Pituitary Carcinoma with Mandibular Metastasis: A Case Report

Pituitary carcinomas are rare primary adenohypophyseal tumors with cerebrospinal or extracranial metastasis. The present case, the first report of the disease in Korea, involved a 36-yr-old woman who presented with a 3-week history of headache. Brain magnetic resonance imaging revealed a 2.5-cm sellar and suprasellar mass showing heterogeneous enhancement with suspicious invasion of both cavernous sinuses. The patient underwent gross-total resection. The tumor cells were composed of polygonal cells singly or in variable-sized nests. The nuclei were large and round with prominent nucleoli. The cytoplasms was acidophilic and granular. Marked pleomorphism and frequent mitoses (3 per 10 HPFs) were found. By immunohistochemistry, tumor cells were strongly positive for prolactin, but negative for ACTH and GH. Additional immunostainings for cytokeratin, vimentin, and glial fibrillary acidic protein (GFAP) were negative. After the surgery, the patient received radiotherapy because of the atypical histologic features. The prolactin level fell from 123.17 ng/mL to 5.17 ng/mL after surgery. Nine months after the initial diagnosis, the patient died from mandibular metastasis associated with the pituitary carcinoma.

Influence of GnRH Agonist and Neural Antagonists on Stress-blockade of LH and Prolactin Surges Induced by 17 beta-estradiol in Ovariectomized Rats

In our previous study, we demonstrated that immobilization stress blocked estrogen-induced luteinizing hormone(LH) surge possibly by inhibiting the synthesis and release of gonadotropin-releasing hormone (GnRH) at the hypothalamic level and by blocking estrogen-induced prolactin (PRL) surge by increasing the synthesis of dopamine receptor at the pituitary level in ovariectomized rats. The present study was performed to determine whether immobilization stress affects pituitary LH responsiveness to GnRH, and whether endogenous opioid peptide (EOP) and dopamine systems are involved in blocking LH and PRL surges during immobilization stress. Immobilization stress was found to inhibit basal LH release and to completely abolish LH surge. However, the intravenous application of GnRH agonist completely restored immobilization-blocked LH surge and basal LH release. Treatment with naloxone did not exert any effect on immobilization-blocked LH surge but increased basal LH release during immobilization stress. Pimozide did not affect immobilization-blocked LH surge or basal LH release. Naloxone also decreased immobilization-induced basal PRL release, but had no effect on immobilization-blocked PRL surge. Immobilization-increased basal PRL levels were augmented by pimozide treatment and immobilization-blocked PRL surge was dramatically restored by pimozide. We conclude that immobilization stress does not impair pituitary LH response to GnRH, and that the immobilization stress-induced blockage of LH surge is probably not mediated by either the opioidergic or the dopaminergic system. However, immobilization-blockade of PRL surge may be partly mediated by the dopaminergic system.

Fine structure of prolactin cell of female albino rat as affected by some antifertility drugs--a comparative electron microscopic study.

One antioestrogenic compound as well as some antifertility drugs have been administered to female albino rats over a period of six months to study their long term effects on fine structures in PRL cell. Almost in all the cases, the dynamics of hormone synthesis and secretion have been affected. Fine structure is suggestive of activation of synthetic machinery of the cell. The cell picture under the estradiol valerate regimen presents a transitional stage progressing towards involution due to accelerated cell cycle. Sparse granulation, frequent granule extrusion and misplaced exocytosis under the influence of tamoxifen citrate or levonorgestrel + ethinyloestradiol are similar to those observed in adenomatous PRL cell. Fine structural correlates of stepped up synthesis are also observed following chronic progesterogenic influences of progesterone and norethisterone heptanoate, but the magnitude of the change is on a lower scale. All the fine structural changes have been discussed in the context of ultrastructural pathology.

Xenoestrogênios: o exemplo do bisfenol-A / Xenoestrogens: the example of bisphenol-A

Evidências acumuladas indicam que a saúde dos seres humanos, animais e espécies selvagens pode sofrer conseqüências adversas da exposição a produtos químicos presentes no meio ambiente e que interagem com o sistema endócrino, tais como bifenilas policloradas, dioxinas, estrogênios de ocorrência natural e sintéticos. Por outro lado, permanecem incertezas científicas com respeito aos dados relatados e, também, quanto à hipótese de haver níveis suficientemente elevados de exposição a estes agentes, a ponto de exercer efeito estrogênico generalizado sobre a população. Este trabalho revisa os principais tópicos relacionados a um dos xenoestrogênios que vem sendo mais recentemente estudado: o Bisfenol A (BFA), um monômero de plástico policarbonato, com pouca homologia estrutural com o estradiol (E 2 ) mas semelhante ao dietilestilbestrol (DES), hexestriol e componente bisfenólico do tamoxifeno. O presente trabalho comenta e analisa criticamente os efeitos do BFA sobre o trato reprodutivo e função lactotrófica em animais de experimentação, à luz das informações disponíveis e experiência do grupo nesta área, e recomenda algumas necessidades de pesquisa.

Role of dopamine in the modulation of adrenal gland responses in the osmotically stressed pigeons, Columba livia.

Salt loading on pigeons (C. livia) had stimulatory effects on brain amines (dopamine and 5-hydroxytryptamine), corticosterone, norepinephrine and epinephrine contents of adrenal gland. Conjoint administration of dopamine with hypertonic saline restored the brain amines and corticosterone of adrenal gland, but had no effect on catecholamine (CAM) contents of adrenal medulla. The excessive release of CAM in the plasma indicates sympathetic stimulation after both the treatments.

Propiedades inmunologicas de la prolactina / Immunological properties of prolactin

La prolactina (PRL) mantiene una marcada interacción bi-direccional con el sistema inmunológico: Estimula la proliferación linfocitaria, estimulando de este modo la respuesta inmune, mientras que sus propias acciones biológicas se hallan bajo el control de citoquinas capaces de modificar la concentración plasmática de PRL. Estos efectos recíprocos implican la presencia de receptores específicos para PRL, presentes en la membrana celular de numerosas clases de linfocitos y células accesorias. La unión de PRL a estos receptores estimula la síntesis y secreción de citoquinas linfocitarias y es un factor de crecimiento esencial para al menos una línea celular linfoide y células accesorias. También se ha demostrado la presencia del mensajero correspondiente a PRL en el citoplasma de linfocitos estimulados por mitógenos, y se ha documentado la efectiva secreción de PRL por células linfoides. La PRL actúa sobre las células NK induciendo su diferenciación hacia células killer activadas por PRL (células PAK) de un modo dosis dependiente (activación a concentraciones fisiológicas e inhibición de la citotoxicidad a concentraciones 10 veces superiores). Además de actuar como un factor de diferenciación de células PAK, la PRL parece modular el efecto promotor de células LAK de la IL-2, y es un potente inductor de la síntesis de interferón gamma e IL-2, lo que sugiere su participación en la génesis de respuestas Th1. Este repertorio de propiedades inmunológicas hace que la PRL sea actualmente considerada como una citoquina, y su participación en la respuesta inmune normal y en numerosos procesos patológicos plantea un importante espectro de potenciales aplicaciones terapéuticas.

Efecto de la hormona liberadora de tirotrofina en la secreción de prolactina de decidua humana / Effect of thyrotropin releasing hormone in the prolactin secretion of human decidua

Para prevenir el síndrome de distress respiratorio (RDS), se ha usado el tratamiento conjunto de betametasona y hormona liberadora de tirotrofina (TRH). La TRH actuaría indirectamente sobre la producción del surfactante pulmonar, estimulando la secreción de hormonas tiroídeas; otra vía para incrementar el surfactante pulmonar es induciendo la secreción de PRL Prolactina (un potente estimulador de la secreción del surfactante pulmonar) desde la hipófisis o de otros tejidos que secreten PRL (como se ha descrito previamente para la decidua). El objetivo de este trabajo fue estudiar el efecto de diferentes dosis de TRH en la secreción de PRL por el tejido corión-decidua y caracterizar las formas bioactivas de PRL secretada por dicho tejido. Veinte placentas de embarazos normales (38-41 semenas), obtenidas por parto normal o cesáreas, fueron recolectadas en el Departamento de Obstetricia y Ginecología del Hospital Clínico de la Universidad de chile. Explantes de tejido corión-decidua secretaron PRL en condiciones basales, con una secreción máxima de la hormona a las 24 horas de incubación. Se encontró un aumento significativo (p<0,05) en la secreción de PRL con 1,5 x 10 elevado 8 M de TRH, el cual fue debido principalmente a un aumento significativo (p<0,05) de la forma little del PRL bioactivo. Estos resultados sugieren que una de las maneras en que TRH acelere la madurez pulmonar fetal podría ser aumentando la secreción de PRL por el tejido decidual; esta hormona podría pasar rápidamente al líquido amniótico para activar la producción del surfactante pulmonar del feto

Effects of oncostatin M on hormone release of rat pituitary cells in primary culture

It has become increasingly clear that cytokines play an important role in modulating neuroendocrine regulation, especially in the secretion of corticotropin (ACTH) in the pituitary. Oncostatin M (OSM), a cytokine of IL-6 family has been reported to increase ACTH secretion and pro-opiomelanocortin (POMC) transcription in murine corticotroph pituitary tumor cells (AtT20 cells). The present study was undertaken to determine the effects of OSM on hormonal release in primary culture of rat pituitary cells. Growth hormone or prolactin release was not affected by OSM. OSM (1 nM) stimulated ACTH release (35.1% increase versus control, p>0.001) in dispersed pituitary cells of rat to a lesser extent than in AtT20 cells. Corticotropin releasing hormone (CRH) (10 nM) also induced a 2.3-fold increase of ACTH secretion (p>0.001), but co-treatment of OSM and CRH did not exhibit any synergistic effect on ACTH secretion. We conclude OSM has a stimulatory effect on ACTH secretion in normal rat pituitary cell cultures, and OSM acts mainly on corticotroph, supporting the potential role of OSM to modulate immune-endocrine regulation in the pituitary.