Características clínicas y manejo de la macroprolactinemia como causa de hiperprolactinemia / Clinical characteristics and management of macroprolactinemia as cause of hyperprolactinemia

La macroprolactinemia se define como la presencia de cantidades elevadas de esta isoforma de la prolactina en suero, en conjunto con concentraciones normales de prolactina monomérica. Se trata de una entidad bastante común, considerada entre las tres primeras causas de hiperprolactinemia. Su origen parece responder a mecanismos autoinmunes y el seguimiento de los pacientes afectos durante periodos de 10 años ha demostrado que es una condición crónica. La prueba de elección para el diagnóstico es la cromatografía líquida en columna de gel, pero este es un método costoso que generalmente es suplido por la prueba de precipitación con polietinglicol. Por mucho tiempo ha prevalecido el concepto de que estos pacientes son esencialmente asintomáticos, pero reportes recientes señalan la presencia de síntomas de hiperprolactinemia como parte significativa del cuadro, aunque la literatura actual muestra criterios divergentes. En estos pacientes la realización de resonancia magnética nuclear hipofisaria parece ser un procedimiento innecesario, basado en la escasa frecuencia de resultados positivos. El tratamiento farmacológico con agonistas dopaminérgicos muestran respuestas contradictorias en cuanto a la desaparición de los síntomas y la normalización de los niveles de prolactina. Por tanto, la inexistencia de un consenso en la literatura científica en lo referente a las manifestaciones clínicas y el manejo, obliga a una conveniente valoración individual de cada caso(AU)

Macroprolactinemia is defined as the presence of high quantities of this prolactin isoform in serum, together with normal concentrations of monomeric prolactin. It is a common entity, considered among the three first causes of hyperprolactinaemia. The origin seems to respond to autoimmune mechanisms and the affected patients follow-up during ten years periods has shown that it is a chronic condition. The standard gold test to the diagnostic is gel-filtration chromatography, but it is an expensive method that is generally supplied by the polyethylene glycol precipitation test. During a long time, the concept that these patients are essentially asymptomatic has prevailed, but recent reports stamps the presence of hyperprolactinemia symptoms as a significant part of the entity, although current literature shows divergent criteria. In these patients, performing pituitary magnetic resonance seems to be an unnecessary procedure, based on the rare frequency of positive results. Pharmacological treatment with dopamine agonists shows contradictory responses with regard to symptoms disappearance and prolactin levels normalization. Therefore, the lack of consensus in the scientific literature with regard to the clinical manifestations and the management, requires a convenient individual assessment of each case(AU)

Osteogenic differentiation of adipose tissue-derived mesenchymal stem cells cultured with different concentrations of prolactin / Diferenciação osteogênica de células tronco mesenquimais do tecido adiposo cultivadas com diferentes concentrações de prolactina

The objective was to evaluate the in vitro effect of prolactin in osteogenic potential of adipose tissue-derived mesenchymal stem cells (ADSCs) in female rats. ADSCs were cultured in osteogenic medium with and without the addition of prolactin and distributed into three groups: 1) ADSCs (control), 2) ADSCs with addition of 100ng/mL of prolactin and 3) ADSCs with addition of 300ng/mL of prolactin. At 21 days of differentiation, the tests of MTT conversion into formazan crystals, percentage of mineralized nodules and cells per field and quantification of genic transcript for alkaline phosphatase, osteopontin, osteocalcin, bone sialoprotein, BMP-2 and collagen I by real-time RT-PCR were made. The addition of prolactin reduced the conversion of MTT in group 3 and increased the percentage of cells per field in the groups 2 and 3, however without significantly increasing the percentage of mineralized nodules and the expression of alkaline phosphatase, osteopontin, osteocalcin, bone sialoprotein, BMP-2 and collagen I. In conclusion, the addition of prolactin in concentrations of 100ng/mL and 300ng/mL does not change the osteogenic differentiation to the ADSCs of female rats despite increase in the cellularity of the culture.(AU)

O objetivo do presente trabalho foi avaliar o efeito in vitro da prolactina sobre o potencial osteogênico de células-tronco mesenquimais do tecido adiposo (CTM-TA) em ratas. CTM-TA foram cultivadas em meio osteogênico com e sem adição de prolactina e distribuídas em três grupos: 1) CTM-TA (controle), 2) CM-TA com adição de 100ng/mL de prolactina e 3) CTM-TA com adição de 300ng/mL de prolactina. Aos 21 dias de diferenciação, foram realizados os testes de conversão do MTT em cristais de formazan, porcentagem de nódulos mineralizados e células por campo e quantificação dos transcritos gênicos para fosfatase alcalina, osteopontina, osteocalcina, sialoproteína óssea, BMP-2 e colágeno I. A adição de prolactina reduziu a conversão do MTT no grupo 3 e aumentou a porcentagem de células por campo nos grupos 2 e 3, sem alterar significativamente a porcentagem de nódulos mineralizados e a expressão de fosfatase alcalina, osteopontina, osteocalcina, sialoproteína óssea, BMP-2 e colágeno I. Conclui-se que a adição de prolactina nas concentrações de 100ng/mL e 300ng/mL não altera a diferenciação osteogênica das CTM-TA de ratas, apesar do aumento de celularidade da cultura.(AU)

Morphometric and hormonal study of the effect of utrica diocia extract on mammary glands in rats / Estudio morfométrico y hormonal del efecto de extracto de utrica diocia en glándulas mamarias en ratas

Urtica diocia is a multipurpose herb in traditional medicine. Its hydroalcoholic extract (20, 50 and 100 mg/kg) administered interaperitoneally to Wistar female rats for 21 consequent days resulted in significant increase in the number of alveoli of mammary glands in doses of 20 and 50 mg/kg. Changes in serum prolactin and alveolar diameter were not significant in comparison with control group. Also, there was an increase in serum prolactin and alveolar diameter in doses of 20 and 50 mg/kg. Utrica diocia extract has positive effects on mammary glands.

Urtica diocia es una hierba de usos múltiples en la medicina tradicional. Su extracto hidroalcohólico (20, 50 y 100 mg/kg) administrado por vía intraperitoneal en ratas hembras Wistar de 21 días resultaron en un aumento significativo en el número de alvéolos de las glándulas mamarias en dosis de 20 y 50 mg/kg. Los cambios en la prolactina sérica y el diámetro alveolar no fueron significativos en comparación con el grupo control. Además, hubo un aumento en la prolactina sérica y en el diámetro alveolar en dosis de 20 y 50 mg/kg. El extracto de Urtica diocia tiene efectos positivos sobre las glándulas mamarias.

Histo-cytological responses of the prolactin cells of the catfish Heteropneustes fossilis to cadmium exposure / Respuesta histológica y citológica frente a la exposición a cadmio de las células prolactínicas del pez gato Heteropneustes fossilis

Cadmium is an important metal for modern industrial processes and, being biologically non-essential, poses health hazards to the organisms. In this study we aimed to evaluate the effect of cadmium exposure on the histo-cytology of prolactin cells in the freshwater catfish, Heteropneustes (H.) fossilis. Fish were subjected to 288 mg/L (0.8 of 96 h LC50) and 72 mg/L (0.2 of 96 h LC50) of cadmium chloride for short-term and long-term, respectively. After sacrificing the fish, the blood was collected on 24, 48, 72 and 96 h in short-term and after 7, 14, 21, and 28 days in long-term experiment and analyzed for plasma calcium levels. Also, pituitary glands were fixed on these intervals. The plasma calcium levels of short-term cadmium exposed fish remain unchanged after 24 h. The levels exhibit a progressive decrease from 48 h onwards. The fish exposed to cadmium for 7 days exhibit a decrease in the plasma calcium level. Thereafter, the levels progressively decrease till the end of the experiment (28 days). The prolactin cells of the control fish exhibit structural resemblance to the description given for the prolactin cells of normal H. fossilis. No change in the histological structure and nuclear volume of prolactin cells of cadmium non-exposed fish has been noticed throughout the experiment. In cadmium treated fish, the prolactin cells remain unchanged till 14 days. On day 21, the nuclear volume of these cells exhibits an increase and the cells degranulate. These changes increased profoundly on day 28. In addition, vacuolization and cytolysis were also encountered on day 28 following cadmium treatment. It is concluded that cadmium affects the prolactin cells of the fish H. fossilis thus disturbing the ionic balance.

El cadmio es un metal importante para los procesos industriales modernos, siendo no esencial biológicamente, representa riesgos para la salud de organismos. En este estudio tratamos de evaluar el efecto de la exposición al cadmio por el aspecto histológico y citológico de células secretoras de prolactinas del pez gato de agua dulce Heteropneustes (H.) fossilis. Los peces fueron sometidos a una exposición de 288 mg/L (0,8 de 96 h CL50) and 72 mg/L (0,2 de 96 h CL50) de cloruro de cadmio por a corto y largo término respectivamente. Después del sacrificio de los peces, la sangre fue colectada, tomando muestras de 24, 48, 72 y 96 hs en el corto término y de 7, 14, 21 y 28 días en las sometidas a largo término, la cuales se analizaron para medir niveles de calcio. Además, las glándulas pituitarias fueron fijadas en esos intervalos El nivel plasmático de calcio en los experimentos de exposición a corto tiempo se mantuvo sin cambio tras 24 h. Los niveles exhibieron una caída progresiva a partir de las 48 hs. Los peces expuestos a cadmio por 7 días presentaron una disminución en el nivel plasmático de calcio. Después de esto, los niveles decayeron progresivamente hasta el fin del experimento (28 días). Las células prolactínicas de los peces controles mostraron semejanza estructural a la descripción dada para estas células normales en H. fossilis. No se observaron cambios en la estructura histológica y el volumen nuclear de las células prolactínicas de los peces no expuestos a cadmio a través de todo el experimento. En los peces tratados con cadmio las células prolactínicas se mantuvieron sin cambios hasta los 14 días. En el día 21, el volumen nuclear de esas células se incrementó y estas células presentaron desgranulación. Estos cambios aumentaron profundamente en las muestras del día 28. Adicionalmente en el día 28 posterior al tratamiento con cadmio se encontró vacuolización y citólisis. Se concluyó en que el Cadmo afecta las cñelupas prolactínicas de H fossilis, produciendo disturbios en el balance iónico.

Prolactin Hormone and Cardiovascular System.

The Prolactin (PRL) hormone, a very ancient hormone, first discovered by Oscar Riddle and his colleagues in the late 1920s, is a 199 amino acid multifunctional polypeptide hormone, that has been found in all vertebrates to influence more than 300 physiologic functions of the body. This review discusses the prolactin structure, mechanism of synthesis, control of secretions, receptors, its intracellular signal transduction and its possible implications on the cardiovascular system.

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.

Immunodetection of Luteinizing Hormone (LH), Follicle-Stimulating Hormone (FSH), Thyroid Stimulating Hormone (TSH) and Prolactin (PRL) in Brachionus calyciflorus (Rotifera: Monogononta)

The endocrine system controls and coordinates behavioral, biochemical, and physiological processes through signal mechanisms using neuropeptides or products of neurosecretory cells. Among invertebrates, this system is poorly studied in rotifers, in which estrogens and androgens significantly affect sexual reproduction. This is the first report of the presence of the Luteinizing Hormone (LH), Follicle-Stimulating Hormone (FSH), Thyroid Stimulating Hormone (TSH) and Prolactin (PRL) in rotifers. Analyses included the avidin-biotin-peroxidase complex method with primary antibodies LH (Anti-Rat LH serum for RIA), PRL (Anti-Rat PRL serum for RIA), FSH (Anti-Rat FSH serum for RIA) and TSH (Anti-Rat TSH serum for RIA). These hormones were found in females, males and parthenogenetic and sexual eggs of the freshwater Brachionus calyciflorus. The immunoreactivity of FSH, LH, TSH and PRL in females was observed in: ovaries, cerebrum, mastax, stomach, lorica, and the stomach gland. However, in males LH was observed only at the trochal disk and cerebrum. The hormones FSH, TSH and PRL, were observed in testicles, contractil vesicles, and cementary gland of males. Regarding amictic or parthenogenetic eggs, the hormones LH, FSH, TSH, and PRL were located mainly in the micromeres, and the staining in the macromeres was weak. On the other hand, in the mictic or sexual eggs the inner shell is stained for the hormones PRL and LH, opposite to the staining of FSH and TSH, located mainly in the embryo. In general, immuno-reactivity was observed in areas important for the reproductive, excretory, digestive and developmental processes. Rev. Biol. Trop. 57 (4): 1049-1058. Epub 2009 December 01.

Se logró detectar la presencia de las hormonas: Hormona Luteinizante (LH), Hormona Folículo Estimulante (FSH), Hormona Estimulante de la Tiroides (TSH) y Prolactina (PRL) en Brachionus calyciflorus siendo el primer reporte de la presencia de dichas hormonas en rotíferos. Estas hormonas fueron identificadas por un método inmunológico-histológico-químico usando el complejo avidina-biotina- peroxidasa con los siguientes anticuerpos primarios: LH (Anti-Rata LH suero para RIA), PRL (Anti-Rata PRL suero para RIA), FSH (Anti-Rata FSH suero para RIA) y TSH (Anti-Rata TSH en suero para RIA). Estas hormonas se encontraron en las hembras, machos, huevos partenogenéticos y huevos sexuales del rotífero dulceacuícola B. calyciflorus. La reactividad inmunológica de FSH, LH, PRL y TSH en las hembras se observó en ovarios, cerebro, mástax, estómago, lorica, y la glándula del estómago. Sin embargo, en machos, la LH se observó sólo en el disco trocal y cerebro mientras que las hormonas FSH, PRL y TSH, se observaron en testículos, vesícula contráctil, y la glándula cementaria. En cuanto a los huevos partenogenéticos o amícticos, las hormonas LH, FSH, TSH, y PRL, se encontraron principalmente en los micrómeros, y en los macrómeros la tinción es débil. Por otra parte, el huevo sexual o míctico muestra reactividad inmunológica en la cubierta interior del huevo para las hormonas LH y PRL, lo contrario para FSH y TSH, las cuales se observaron principalmente en el embrión. La reactividad inmunológica fue observada, en general, en áreas importantes para los procesos reproductivos, excretorios, digestivos y del desarrollo.

[Diagnostic value of prolactin and B-HCG levels of vaginal fluid in diagnosis of premature rupture of membranes]

The aim of this study was diagnosis of premature rupture of membranes in suspected patients by measurement of prolactin and B-hCG levels in vaginal washing in order to reduce perinatal mortality and morbidity. The study included 211 pregnant women who were referred to the emergency of Imam Hossein Hospital at 28-38 weeks of pregnancy for leakage or prenatal care from April, 2007 to April 2008. The expulsion of fluid from the cervix was evaluated and fern and nitrazin tests were done. B-hCG and prolactin levels of vaginal washing fluid were measured. The presence of 2 of 3 parameters of fern test, nitrazin and cervical fluid was defined as absolutely premature rupture of membranes. Man-Withney U-test was used for analysis. The Roc curve was calculated. There were 132 patients in PROM group and 79 patient in the control group. The average age in the PROM and control groups was 26.9 +/- 6.08 and 26.2 +/- 4.84 years, respectively [P=0.074]. Both groups were matched for parity and gravidity. Prolactin levels in PROM group were 2930 +/- 3737 mIU/l versus 23.18 +/- 120mIU/l in the control group [P=0.000]. B-hCG was 439.78 +/- 1867mIU/l in PROM and 17.72 +/- 30mIU/l in control group [p=0.000]. Sensitivity and specificity of prolactin according to cut-off of 16.0mIU/l was 79.41% and 96%, respectively. Sensitivity and specificity for B-hCG with cut-off point of 12.5 was 69.85% and 69.33%, respectively. The measurement of prolactin and B-hCG levels in patients with suspected premature rupture of membranes can help in decision-making and treatment

Evaluación por inmunohistoquímica de la expresión de hormonas hipofisiarias y del marcador de proliferación celular Ki-67 en tejido de adenomas causantes de acromegalia / Immunohistochemistry for pituitary hormones and Ki-67 in growth hormone producing pituitary adenomas

Background: Growth hormone (GH) producing adenomas, frequently express several hormones. This condition could confer them a higher proliferative capacity. Ki-67 is a nuclear protein antigen that is a marker for proliferative activity. Aim: To measure the immunohistochemical hormone expression in pituitary adenomas, excised from patients with acromegaly. To determine if the pluríhormonal condition of these adenomas is associated with a higher proliferative capacity, assessed through the expression of Ki-67. Material and methods: Forty one paraffin embedded surgical samples of pituitary adenomas from patients with acromegalia were studied. Immunohistochemistry for GH, prolactin (PRL), follicle stimulating hormone (FSH), luteinizing hormone (LH), thyroid stimulating hormone (TSH), adrenocorticotropin (ACTH) and for the expression of Ki-67 was carried out. Results: All samples were positive for GH. Twenty seven had positive staining for PRL, 12 had positive staining for glycoproteic hormones and 11 for PRL and one or more glycoproteic hormones. Mean staining for Ki-67 was Z.6±3.3 percent. There were no differences in the expression of this marker between mono or pluríhormonal tumors. The expression was neither associated with extrasellar extensión. Conclusions: Half of GH producing pituitary adenomas are pluríhormonal. There are no differences in the expression of Ki-67 between mono and plurihormonal adenomas.

Treatment outcome of hyperprolactinaemic infertility with carbegoline in sub saharan Africa

Hyperprolactinaemia is a known cause of infertility. We explored the efficacy of carbegoline, the long acting dopamine agonist that was recently introduced into our medical practice. Seventy six patients with infertility secondary to hyperprolactinaemia were studied over a period of 20 weeks each. All the patients had carbegoline twice weekly for eight weeks. Two dosage regimen were used based on the pretreatment prolactin level; less than 50ng/ml had 0.25mg twice weekly [n=58] and 50ng/ml and above 0.5mg twice weekly [n=18]. Normalization of prolactin level was achieved in 75 [98.7%] patients. At the end of the study period, there was resumption of menstrual flow in 10 [76.9%] of the 13 patients that were amenorrhoiec and all the 39 [100%] patients that were oligomenorrhoeic had their normal menstrual cycle restored. Resumption of ovulatory cycles occurred in 87.7% of those with anovulatory cycles. Of the 76 patients, 69 [90.8%] got pregnant during the 20 weeks study. However, out of the 69 that got pregnant, 13 [18.8%] got pregnant while on carbegoline therapy. There was no case of carbegoline resistance or discontinuation recorded in this study. Carbegoline is a cost effective first line therapy in the management of infertile women with hyperprolactinaemia

Prolactin and cortisol levels in women with endometriosis

Endometriosis is a progressive estrogen-dependent disease affecting women during their reproductive years. The objective of the present study was to investigate whether endometriosis is associated with stress parameters. We determined cortisol and prolactin levels in serum, peritoneal and follicular fluid from infertile women with endometriosis and fertile women without the disease. The extent of the disease was staged according to the revised American Fertility Society classification (1997). Serum and peritoneal fluid were collected from 49 women aged 19 to 39 years undergoing laparoscopy. Eighteen women had stage I-II endometriosis and 10 had stage III-IV. Controls were 21 women undergoing laparoscopy for tubal sterilization. Follicular fluid was obtained from 39 women aged 25-39 years undergoing in vitro fertilization (21 infertile women with endometriosis and 18 infertile women without endometriosis). Serum prolactin levels were significantly higher in infertile women with stage III-IV endometriosis (28.9 ± 2.1 ng/mL) than in healthy controls (13.2 ± 2.1 ng/mL). Serum cortisol levels were significantly higher in infertile women with stage III-IV endometriosis (20.1 ± 1.3 ng/mL) than in controls (10.5 ± 1.4 ng/mL). Cortisol and prolactin levels in follicular fluid and peritoneal fluid did not differ significantly between groups. The high levels of cortisol and prolactin in the serum from women with endometriosis might contribute to the subfertility frequently associated with the disease. Moreover, since higher levels of cortisol and prolactin are often associated with stress, it is probable that stress might contribute to the development of endometriosis and its progression to advanced stages of the disease.

Macroprolactina, um método de diferenciação de prolactinas de elevado peso molecular pela precipitação por`Polietilenoglicol / Macroprolactine, a method to detect prolactines de high molecular weight with precipitation with poliethylenoglycol

Um estudo realizado no setor de hormônios do Laboratório de Análises Clínicas do Hospital Geral de Brasília adaptou para equipamentos de quimioluminescência o método de precipitação por polietilenoglicol em soros de pacientes com hiperprolactinemia para detecção de isoformas da prolactina com elevado peso molecular (macroprolactina), evitando, com isto, estudos de imagens para confirmação diagnóstica.

A research made in the hormony sector of the Laboratorty of Clinical Analisys of th Hospital Geral de Brasília of the Defense Ministery had adapted the method of precipitation with poliethylenoglycol (PEG 6000) in serum of patients with hyperprolactinemia for chemiluminescence equipments in order to detect the isoforms of prolactine with high moleculer weight (macroprolactine), avoiding, with this, image studies to confirm diagnosis.

Hormona del crecimiento y prolactina en líquido amniótico y plasma materno durante el embarazo normal / Growth hormone and prolactin in maternal plasma and amniotic fluid during normal gestation

Objective. To measure the concentration of human growth hormone (GH) and prolactin (PRL) In maternal plasma (MP) and amniotic fluid (AF) during gestation and to evaluate their correlation. Methods. HC and PRL were measured by radioimmunoassay in 60 healthy women with uncomplicated singleton pregnancies at 16-36 weeks of gestation (WG). Trends of both hormones were estimated throughout pregnancy. The correlation of either hormone measured in different fluids was also estimated. Results. GH in AF (AF-GH) decreased significantly throughout pregnancy; (AF-GH = 21.32 - 0.54 X WG, r = -0.72 [95% confidence intervals (95% CI) -0.57-0.82], p = 0.001), and increased in MP (MP-GH); (MP-GH = 2.73 +0.11 X WG, r = 0.45 [95% CI, 0.21-0.63]p = 0.05). The correlation between MP-GH and AF-GH was, (AF-GH = 16.28 - 1.54 x - M-PGH, r = -0.47 [95% CI, -0.64 --0.21]; p = 0.01). PRL values did not show significant differences neither in AF (AF-PRL / WG, r = 0.06, p = 0.6) nor in MP (MP-PRL / WG, r = 0.25, p = 0.14) during pregnancy, being AF-PRL (mean 151.3 ng/mL, SD 34.2 ng/mL) significantly higher than MP-PRL (mean 119.3 ng/mL, SD 55.4 ng/mL) (p = 0.006) in all the studied period. Conclusion. AF-GH and MP-GH showed a significant negative correlation during pregnancy. PRL measured in AF and PM did not show changes throughout gestation being AF-PRL significantly higher than MP-PRL.

Objetivo. Medir los valores de hormona del crecimiento (HC) y prolactina (PRL) en el líquido amniótico (LA) y en el plasma materno (PM) durante el embarazo normal y analizar sus asociaciones. Métodos. HC y PRL fueron medidas en el LA y en el PM por medio de radioinmunoanálisis en 60 mujeres con embarazo único y sin complicaciones entre 16 y 36 semanas de gestación (SG). Se evaluaron las tendencias de ambas hormonas a lo largo del embarazo y la correlación entre los valores obtenidos en ambos compartimentos. Resultados. La HC en LA (HCLA) disminuyó en forma significativa durante el embarazo (HCLA = 21.32 - 0.54 X SG, r = -0.72 [intervalos de confianza al 95% (IC 95%) -0.57-0.82], p = 0.001) y en PM (HCPM) aumentó (HCPM = 2.73 + 0.11 X SG, r = 0.45 [IC 95%, 0.21-0.63] p = 0.05). La correlación entre los valores de HC en LA y en PM fue: (HCLA = 16.28-1.54 x -HCPM, r = -0.47 [IC 95% -0.64 -0 -0.21]; p = 0.01). La concentración de PRL a lo largo del embarazo tanto en LA (PRL-LA/SG, r = 0.06, p = 0.6) como en PM (PRL-PM/SG r = 0.25, p = 0.14) no cambió y fue significativamente más alta en LA que en PM (LA; media 151.3 ng/mL, DE 34.2 ng/ inL, PM; media 119.3 ng/mL, DE 55.4 ng/mL, respectivamente, p = 0.006). Conclusiones. HC en PM y HC en LA presentan una correlación inversa a lo largo del embarazo, en tanto que los valores de PRL en ambos compartimentos no cambian, siendo significativamente más elevados en el LA.

Estudo da atividade biológica da macroprolactina humana em células Nb2 e em células Ba/F03 transfectadas com o receptor de prolactina humano forma longa / Human macroprolactin biological activity study in Nb2 cells and in Ba/F-03 cells expressing human long prolactin receptor

A macroprolactinemia é condição freqüente na hiperprolactinemia e em geral, sem impacto clínico. Os dados sobre a atividade biológica da macroprolactina (bbPRL) são controversos e baseados em bioensaio heterólogo com células de rato Nb2. A atividade biológica da bbPRL é observada in vitro e não in vivo, provavelmente porque seu alto peso molecular evita sua passagem pelos capilares. A bioatividade da bbPRL talvez varie de acordo com a especificidade do receptor de prolactina (PRLR). Avaliamos a bioatividade da bbPRL de indivíduos macroprolactinêmicos (Grupo I, n = 18) e da PRL monomérica (mPRL) de pacientes hiperprolactinêmicos sem bbPRL (Grupo II, n = 5) em Nb2 e em células Ba/F-LLP, transfectadas com o PRLR humano. Enquanto ambos ensaios apresentam resultados similares para a atividade de mPRL, nossos resultados indicam que a atividade da bbPRL é presente em ensaio heterólogo e não em ensaio homólogo. O ensaio Ba/F-LLP é sensível e apresenta melhor correlação com a atividade in vivo da bbPRL /Macroprolactinemia is a frequent finding in hyperprolactinemic individuals, usually without clinical impact. Data on biological activity of macroprolactin (bbPRL) is mostly based on a heterologous bioassay (Nb2 cell). Biological activity of bbPRL observed in vitro but not in vivo maybe due to its high molecular weight preventing its passage through capillary barrier. Alternatively, bbPRL bioactivity may differ depending on the PRL receptor species specificity. BbPRL from macroprolactinemic individuals and monomeric PRL (mPRL) from hyperprolactinemic patients without macroprolactinemia were tested in two bioassays: Nb2 and in Ba/F-LLP, which expresses human prolactin receptor. While both bioassays achieve similar results considering mPRL activity, our results indicate that bbPRL displays activity in a heterologous but not in a homologous bioassay, consistently with the apparent absence of bbPRL bioactivity in vivo...

La macroprolactina, diagnóstico diferencial de la hiperprolactinemia / The macroprolactina, differential diagnosis of the hyperprolactinaemia

La macroprolactina es una isoforma de la prolactina (PRL) humana que se encuentra en escasa proporción en el plasma y que en algunos pacientes se puede encontrar anormalmente elevada, causando hiperprolactinemia, que puede presentarse como asintomática, pero también presentar sintomatología dada por el exceso de prolactina, también ha sido relacionada a adenomas hipofisiarios. Por esta causa es necesario contar con métodos confiables para su detección y medición. El origen de esta macromolécula, patogenia, regulación hormonal e historia natural aun no está esclarecido, se postula que corresponde a un complejo antigénico IgG-PRL, con bioactibidad reducida.El Gold Standard para la determinación de la macroprolactina es la Cromatografía de filtración en gel, pero su uso se restringe a la investigación por su alto costo y tiempo de desarrollo. Existen otros métodos para su detección, siendo hasta ahora el de precipitación por Polietilenglicol el más aceptado.

Macroprolactin is an isoform of human prolactin (PRL) existing in low doses in plasma. In some patients, prolactine can be found in higher proportion, causing hyperprolactinaemia, in asyntomaticor symptomatic form. This abnormality has been also related to hypophysis adenome, doing necessary to count on reliable methods for its detection and measurement. The origin of this macromolecule, patogenia, hormonal regulation and natural history are not even clear, an antigenic complex IgG-PRL with reduced bioactivity is proposed. The Gold Standard for determination of macroprolactin is gel filtration chromatography, but its high costs and slowness restricts its use toresearch. Other methods for its detection already exist, the Polyethylene glycol precipitation is beingmostly accepted.

Impacto de la hemodilución en recuentos leucocitarios y niveles de cortisol, prolactina e IL-6. Comparación entre dos técnicas anestésicas en colecistectomías videolaparoscópicas / Impact of hemodilution in leukocyte count and levels of cortisol, prolactine and IL-6. Comparison between two anesthesia techniques in videolaparoscopic cholecystectomies

Introducción: Los aportes hidroelectrolíticos durante la cirugía varían con el método anestésico utilizado, generando cambios diferentes. Se han descripto diversas fórmulas de ajuste para estimar con mayor precisión los cambios observados durante las cirugías con anestesia total endovenosa (E) o inhalatoria (Inh). Objetivos: Evaluar la bondad del ajuste para analizar y cuantificar el impacto sobre componentes sanguíneos, tanto séricos como celulares, causado por la hemodilución producida por la hidratación intra y postoperatoria en dos grupos de pacientes quirúrgicos sometidos a colecistectomías videolaparoscópicas (CVL) y asignados a diferentes técnicas anestésicas. Pacientes y métodos: Pacientes programados para CVL a las 7:30 AM, 20-65 años, ASA I. Técnica Anestésica: Grupo E: propofol, remifentanilo y vecuronio (n= 14), Grupo Inh: propofol, fentanilo e isoflurano (n= 13). Se hicieron las siguientes tomas de muestras de sangre: basal, intraoperatoria (i.o.), 1er. y 7° día postoperatorio; los parámetros de laboratorio evaluados fueron hemograma, recuentos linfocitarios (CD3, CD4, CD8 y CD20) y nivel sérico de cortisol, prolactina e IL-6. Se ajustaron los valores al hematocrito basal según la fórmula: valor ajustado = valor de la variable x hematocrito basal / hematocrito del momento en estudio. Se compararon los valores con y sin ajuste por test no paramétricos. Resultados: Sólo en los pacientes del grupo E disminuyó significativamente el hematocrito con respecto al basal (media ± desvío estándar: 39,2 ± 5,6), en el intraoperatorio, IO (35,9 ± 5,2, P = 0.0019) y en el primer día posquirúrgico (36,9 ± 4,3, P = 0,013). El ajuste por hemodilución reveló diferencias significativas entre los tratamientos anestésicos en el IO en lo que se refiere al porcentaje de neutrófilos (E: 74,7 ± 12, Inh: 61,7 ± 12; P = 0.048) yen el LCD4+ (E: 53,2 ± 11, Inh: 41,5 ± 15; P = 0.025) que no se habían identificado en los datos originales, mientras que el ajuste no modificó la información relativa al resto de las determinaciones analizadas. Conclusión: Dadas las diferencias encontradas entre los tratamientos anestésicos y la simplicidad del ajuste, sugerimos la conveniencia de realizar dicho ajuste tanto en el análisis de los valores del recuento de células como de factores solubles de sangre periférica críticos durante el postoperatorio.

Efeito do tabagismo sobre a liberação de prolactina, produção láctea e componentes imunes do leite de ratas / Effect of tobacco smoke on prolactin levels, milk production and immune composition in rats

Para avaliar os efeitos do tabagismo passivo na lactação, ratas foram expostas durante a gravidez e a lactação a um sistema de inalação de fumaça lateral do cigarro. Foram avaliados peso materno no período, crescimento dos filhotes na gestação e lactação, produção de leite, níveis de IgA sérico e lácteo e o efeito do tabaco sobre a liberação de prolactina mediada pela sucção. Foi observado que a exposição ao tabaco comprometeu o ganho de peso materno, o peso e comprimento ao nascer e o crescimento posterior dos filhotes, de forma mais intensa que o simples manuseio. A produção de leite e os níveis de IgA também foi prejudicada. O retardo na liberação de prolactina observado pode estar associado a exposição ao tabaco ou ao estresse do modelo experimental/In order to evaluate the passive smoking effect on lactation, rats were exposed from pregnancy through lactation to tobacco sidestream smoke. Mother weight, pups weight and length, milk production, seric and milk IgA and tobacco effect on prolactin release under sucking stimulus were measured. It was observed that tobacco exposure more intensively than experimental handling, compromised mother weight gain and pup growth. Milk production was also damaged. A relapse in prolactin release was observed and may be associated to tobacco exposure but also to animal experimental stress...

The effect of telomerase expression on the escape from M2 crisis in virus-transformed human retinal pigment epithelial cells

Integrins are heterodimeric glycoproteins that have been found to undergo dynamic temporal and spatial changes in the endometrium during the menstrual cycle and in early pregnancy. Specificity of integrins is known to be different in human endometrial stromal cells and decidual cells. These shifts of integrins suggested to play an important role in embryo implantation and can be modulated by progesterone, cAMP derivatives, and cytokines. The mechanisms of decidualization and its precise physiological role are still not clearly understood and in vitro systems could provide an alternative that overcomes limitations of studying such complex biological phenomena in vivo at the time of implantation. This study was undertaken to establish an in vitro model system for human decidualization using 8-bromo-cAMP and to investigate the characteristics of stromal integrin expression in vitro by 8-Br-cAMP. Endometrial stromal cells were isolated and cultured, and then were induced to decidualize by 0.5 mM 8-Br-cAMP for 15 days. Immunofluorescence staining and flow cytometric analyses of the integrin subunits (alpha1, alpha4, alpha5, alpha6, beta1 and alpha v beta3) were performed at day 9. In the presence of 8-Br-cAMP, the staining intensity of alpha v beta3 was significantly higher than control and measurements for alpha1, alpha4, alpha5, alpha6, and beta1 were similar. Immunofluorescent localization of the integrins reflected the differences obtained from the flow cytometric analyses described above. In summary, the expression of alpha;avbeta;b3 integrin increased in stromal cells in vitro decidualized by 8-Br-cAMP and this up-regulation of alpha v beta3 integrin expression during decidualization might influence on human implantation.

Is the infertility in hypothyroidism mainly due to ovarian or pituitary functional changes?

The objective of the present study was to examine whether hypothyroidism affects the reproductive system of adult female rats by evaluating ovarian morphology, uterus weight and the changes in serum and pituitary concentrations of prolactin and gonadotropins. Three-month-old female rats were divided into three groups: control (N = 10), hypothyroid (N = 10), treated with 0.05 percent 6-propyl-2-thiouracil (PTU) in drinking water for 60 days, and T4-treated group (N = 10), receiving daily sc injections of L-thyroxine (0.8 æg/100 g body weight) during the last 10 days of the experiment. At the end of 50 days of hypothyroidism no hypothyroid animal showed a regular cycle, while 71 percent of controls as well as the T4-treated rats showed regular cycles. Corpora lutea, growing follicles and mature Graafian follicles were found in all ovaries studied. The corpora lutea were smaller in both the hypothyroid and T4-replaced rats. Graafian follicles were found in 72 percent of controls and only in 34 percent of hypothyroid and 43 percent of T4-treated animals. Serum LH, FSH, progesterone and estradiol concentrations did not differ among the three groups. Serum prolactin concentration and the pituitary content of the three hormones studied were higher in the hypothyroid animals compared to control. T4 treatment restored serum prolactin concentration to the level found in controls, but only partially normalized the pituitary content of gonadotropins and prolactin. In conclusion, the morphological changes caused by hypothyroidism can be a consequence of higher prolactin production that can block the secretion and action of gonadotropins, being the main cause of the changes observed