Atypical pituitary hormone-target tissue axis / 医学前沿

A long-held belief is that pituitary hormones bind to their cognate receptors in classical target glands to actuate their manifold functions. However, a number of studies have shown that multiple types of pituitary hormone receptors are widely expressed in non-classical target organs. Each pituitary gland-derived hormone exhibits a wide range of nonconventional biological effects in these non-classical target organs. Herein, the extra biological functions of pituitary hormones, thyroid-stimulating hormone, follicle-stimulating hormone, luteinizing hormone, adrenocorticotrophic hormone, and prolactin when they act on non-classical organs were summarized, defined by the novel concept of an "atypical pituitary hormone-target tissue axis." This novel proposal explains the pathomechanisms of abnormal glucose and lipid metabolism, obesity, hypertension, fatty liver, and atherosclerosis while offering a more comprehensive and systematic insights into the coordinated regulation of environmental factors, genetic factors, and neuroendocrine hormones on human biological functions. The continued exploration of the physiology of the "atypical pituitary hormone-target tissue axis" could enable the identification of novel therapeutic targets for metabolic diseases.

Studies on the reproductive and developmental biology of Cichlasoma dimerus (Percifomes, Cichlidae): [review]

Many characteristics of the South American teleost fish Cichlasoma dimerus (body size, easy breeding, undemanding maintenance) make it amenable to laboratory studies. In the last years, many of the fundamental aspects of its reproductive and developmental biology have been addressed in our laboratory. Rather recently, the immunohistochemical localization of pituitary hormones involved in reproduction and in background color adaptation has been described in both adult and developing individuals, and the role of FSH in ovarian differentiation has been established. These findings have been correlated with mapping of some of their brain-derived controlling hormones. The latter include brain-derived gonadotropins which were shown to be active in vitro in the control of pituitary hormone secretions. The emerging picture shows C. dimerus as an interesting species in which many of their basic features have already been investigated and which conform a solid platform for comparative studies correlating neurohormones, pituitary hormones and behavior, from the molecular to the organismic level.

The Characteristics of Incidental Pituitary Microadenomas in 120 Korean Forensic Autopsy Cases

To investigate the characteristics of incidental pituitary microadenomas, we examined 120 pituitary glands from Korean forensic autopsy cases, from which eight tumors were identified (incidence 6.7%). The average age of the affected subjects was 50 yr (range: 33-96 yr) with a female predominance. The maximum diameters of the tumors ranged from 0.4 to 5.4 mm (mean: 2.8 mm). Immunohistochemical analysis of pituitary hormones revealed three growth hormone-secreting adenomas, one prolactin-producing adenoma, one gonadotropin-producing adenoma, one plurihormonal adenoma, and two null cell adenomas. MIB-1 staining for Ki-67 antigen showed no positive expression. The microvessel density (MVD) of the pituitary microadenomas ranged from 2.3 to 11.6% (mean: 5.3%) and was significantly lower than that of nonneoplastic pituitary glands (11.9-20.1%, mean: 14.8%). Our study provides reference data on incidental pituitary microadenomas in the Korean population.

Pituitary cell type-specific electrical activity, calcium signaling and secretion

All secretory anterior pituitary cells exhibit spontaneous and extracellular calcium-dependent electrical activity, but differ with respect to the patterns of firing and associated calcium signaling and hormone secretion. Thus, somatotrophs and lactotrophs fire plateau-bursting action potentials spontaneously and without coupling to calcium release from intracellular stores, which generate calcium signals of sufficient amplitude to keep steady hormone release. In these cells, both spontaneous electrical activity and basal hormone secretion can be further amplified by activation of Gq/11 and Gs-coupled receptors and inhibited by Gi/o/z-coupled receptors. In contrast, gonadotrophs fire single, high-amplitude spikes with limited ability to promote calcium influx and exocytosis, whereas activated Gq/11-coupled receptors in these cells transform single-action potential spiking into the plateau-bursting type of electrical activity and trigger periodic high-amplitude calcium signals and exocytosis of prestored secretory vesicles. Here, we review biochemical and biophysical aspects of spontaneous and receptor-controlled electrical activity, calcium signaling, and hormone secretion in pituitary cells.

Caracterização clínica e imunoistoquímica dos adenomas clinicamente não-funcionantes de hipófise / Non-functioning pituitary adenomas: clinical features and immunohistochemistry

Adenomas clinicamente não-funcionantes de hipófise, não produzem clínica de hipersecreção hormonal. Por esse motivo, seus sinais e sintomas dependem de seu efeito de massa no sistema nervoso central. A sua etiopatogenia é complexa com vários fatores provavelmente influenciando seu desenvolvimento como os hormônios hipotalâmicos (GHRH), fatores de crescimento (FGF), fatores de proliferação (PCNA, e KI-67), proteína P53 e proto-oncogene c-erb-B2. OBJETIVOS: 1) Determinar as características clínicas da população de 117 pacientes tratados com adenoma clinicamente não-funcionante de hipófise (idade, sexo, tamanho do tumor, número de procedimento cirúrgico, desenvolvimento de deficiência hormonal e hiperprolactinemia). 2) Identificar, após a caracterização clínica desses pacientes, aqueles com adenoma clinicamente não-funcionante que apresentam imunoistoquímica positiva para os hormônios hipofisários PRL LH, FSH, GH, TSH e ACTH. 3) Precisar nessa população a positividade imunoistoquímica para o fator de proliferação celular Ki-67, para a proteína P53 e para a proteína C-erb-B2 correlacionando a sua positividade com o tamanho e invasão tumoral. Dessa forma avaliando o valor prognóstico desses fatores de proliferação. 4) Confrontar os resultados da imunoistoquímica realizada através do bloco padrão com os resultados da imunoistoquímica obtidos através do tissue micro-array. MÉTODO: Estudo das características clínicas de 117 pacientes com adenoma clinicamente não-funcionate de hipófise (idade, sexo, tamanho do tumor, número de procedimento cirúrgico, desenvolvimento de deficiência hormonal e hiperprolactinemia). Estudo imunoistoquímico (H&E) de 39 pacientes para hormônios hipofisários, para a proteína P53, proteína C-erb-B2, Ki-67 e sua correlação com crescimento tumoral. A seguir, também foi realizado o tissue micro-array dos 39 casos, estudados anteriormente, com imunoistoquímica para os hormônios hipofisários, para a proteína P 53, proteína C-erb-B2, Ki-67 e sua correlação com o crescimento tumoral. RESULTADOS: Não houve diferença estatisticamente significante entre os sexos masculino e feminino com relação à idade, tamanho tumoral e número de procedimentos cirúrgicos (p=0,279, p=0,813, p=0,139 respectivamente)...

Regulation of pituitary hormones and cell proliferation by components of the extracellular matrix

The extracellular matrix is a three-dimensional network of proteins, glycosaminoglycans and other macromolecules. It has a structural support function as well as a role in cell adhesion, migration, proliferation, differentiation, and survival. The extracellular matrix conveys signals through membrane receptors called integrins and plays an important role in pituitary physiology and tumorigenesis. There is a differential expression of extracellular matrix components and integrins during the pituitary development in the embryo and during tumorigenesis in the adult. Different extracellular matrix components regulate adrenocorticotropin at the level of the proopiomelanocortin gene transcription. The extracellular matrix also controls the proliferation of adrenocorticotropin-secreting tumor cells. On the other hand, laminin regulates the production of prolactin. Laminin has a dynamic pattern of expression during prolactinoma development with lower levels in the early pituitary hyperplasia and a strong reduction in fully grown prolactinomas. Therefore, the expression of extracellular matrix components plays a role in pituitary tumorigenesis. On the other hand, the remodeling of the extracellular matrix affects pituitary cell proliferation. Matrix metalloproteinase activity is very high in all types of human pituitary adenomas. Matrix metalloproteinase secreted by pituitary cells can release growth factors from the extracellular matrix that, in turn, control pituitary cell proliferation and hormone secretion. In summary, the differential expression of extracellular matrix components, integrins and matrix metalloproteinase contributes to the control of pituitary hormone production and cell proliferation during tumorigenesis.

First Male Case of Lymphocytic Hypophysitis in Korea

Lymphocytic hypophysitis is a rare inflammatory disorder which is caused by autoimmune destruction of the pituitary gland. Almost all reported cases have been in women and the disease is often associated with pregnancy. We describe here the first male case of lymphocytic hypophysitis in Korea. The patient presented with headache, impotence, decreased libido, and deteriorated vision. Endocrinologic studies showed panhypopituitarism, and pituitary MRI imaging revealed a homogeneously enhanced pituitary mass with a thickened stalk. Treatment with prednisolone and thyroid hormone for five months was ineffective. Transsphenoidal resection of the pituitary mass was performed successfully with normalization of the visual field defect. Histologic examination revealed diffuse lymphocytic infiltration with dense collagenous fibrosis, consistent with lymphocytic hypophysitis. Lymphocytic hypophysitis should be considered in differential diagnosis even in men with hypopituitarism and an enlarged pituitary gland.

Drug induced endocrine problems.

Drug induced effects on the various endocrine and metabolic processes constitute a very common differential diagnostic possibility in investigating endocrine disorders. Knowledge of drug-effect is of paramount importance to avoid unnecessary and expensive investigations and treatment. Since most of the effects are type A effects and hence predictable, reduction of dose or modification of therapy is sufficient to reverse the adverse effects.

Cuantificación de hormonas tiroideas y tirotropina en niños críticamente enfermos con septisemia / Quantification of the thyroid hormones and thyrotropine in critically-ill septicemic children

Estudiamos la función hipotálamo, hipofisiaria, tiroidea en 23 niños críticamente enfermos con septicemia y 15 controles sin patología que afectara dicho eje. La comparación de los resultados de las cuantificaciones de 3,3'5-triiodotironina (T3), 3,3'-5'-triiodotironina evidenció franca disminución de T3 y T4 y elevación de T3r y TSH en los septicémicos, con diferencia estadísticamente significativa (P<0.001). Estas alteraciones bioquímicas que traducen un mecanismo del organismo para mantener la homeostasis y evitar el cataolismo, mediante la conservación de energía, mostraron su normalización espontánea en 18 sobrevivientes de los niños septicémicos al recuperarse

Interaction between inhibin and melatonin on secretion of rat pituitary gonadotrophins.

In presence of melatonin, the suppression of FSH levels by inhibin is reduced (31%) as compared to inhibin given alone (51%) to adult male rats. Likewise, inhibin decreases the prolactin enhancement following melatonin administration. These experiments demonstrate interaction of inhibin and melatonin on the secretion of pituitary gonadotrophins.

Evidence for melanin concentrating hormone (MCH) receptors mediating melanosome aggregation in Labeo melanophores.

Melanin concentrating hormone (MCH: 5 x 10(-12)-5 x 10(-8) M) induced a concentration related, rapid and reversible pigment aggregation in innervated melanophores of Labeo rohita. In inducing melanosome aggregation MCH was found to be 10(4) times more potent than norepinephrine. Experiments employing phentolamine and propranolol suggest that MCH acts through its own specific receptors on the melanophores unrelated to adrenoceptors. MCH was able to aggregate the melanosomes even in the absence of extracellular Ca2+.

Estudio hormonal en 100 pacientes con adenoma hipofisario tratados por medios quirúrgicos / Hormonal study in 100 patients with hypophyseal adenoma treated by surgical means

Se realizaron los estudios hormonales y los resultados terapéuticos de 100 pacientes con adenoma hopofisario tratados quirúrgicamente, de los cuales 41 correspondieron a acromegalia, 15 a prolactinoma, 12 a enfermedad de Cushing y 32 a adenoma inactivo. Cuarenta y dos pacientes tuvieron adenoma intrasillar y 58 presentaron extensión extrasillar. Se obtuvieron mejores resultados entre los adenomas intrasillares, principalemnte en acromegalia con 96 por ciento de curación, mientras en el prolactinoma y en el adenoma inactivo se logro en 50 por ciento y en la enfermedad de Cushing en 43 por ciento. Por otra parte, en los adenomas con extensión extrasillar los resultados en general fueron menos satisfactorios. ocurrió diabetes insípida transitoria en 43 por ciento de los pacientes, y fue ésta complicación más frecuente. También se encontraron hipotiroidismo secundario en 29 pacientes, insuficiencia suprarrenal en 26 e hipogonadismo em 22, en la mayor parte de los cuales ya estaba presente antes de la operación. Diez pacientes murieron, principalmente por infección y daño neurológico