Efeito da hiperprolactinemia induzida pela metoclopramida na córnea de camundongas / Effects of metoclopramide-induced hyperprolactinemia on the murine corneal

OBJETIVO: Avaliar as alterações morfológicas promovidas pela hiperprolactinemia induzida pela metoclopramida na córnea de camundongas durante a fase de proestro e na gestação. MÉTODOS: Quarenta camundongas adultas foram divididas, aleatoriamente, em dois grupos, a saber: controle (CTR1) e metoclopramida (MET1). Após 50 dias metade dos animais de cada grupo foram sacrificados. O restante dos animais foi acasalado, constituindo dois grupos: controle prenhe (CTR2) e o metoclopramida prenhe (MET2), que foi sacrificado no 6° dia de gestação. Após decapitação dos animais coletou-se sangue para dosagens de estradiol, progesterona e prolactina, em seguida removidos os globos oculares para estudo histomorfométrico da córnea. RESULTADOS: As espessuras do epitélio, estroma, endotélio e a espessura total das córneas dos grupos experimentais: MET1 e MET2 mostraram-se mais espessados quando comparados com os grupos controles: CTR1 e CTR2, respectivamente. Houve redução dos níveis hormonais do estrogênio e da progesterona nos animais que receberam metoclopramida em comparação com os respectivos controles (CTR1: estradiol = 156,6±42,2 pg/ml; progesterona = 39,4±5,1 ng/ml; prolactina = 130,4±26,2 ng/ml; MET1: estradiol = 108,0±33,1 pg/ml; progesterona = 28,0±6,4 ng/ml; prolactina = 551,5± 23,3 ng/ml; CTR2: estradiol = 354,0±56,0 pg/ml; progesterona = 251,0± 56,0 ng/ml; prolactina = 423,2±28,1 ng/ml; MET2: estradiol = 293,0± 43,0 pg/ml; progesterona = 184,0±33,0 ng/ml; prolactina = 823,1±51,1 ng/ml). CONCLUSÃO: A hiperprolactinemia induzida pela metoclopramida produziu espessamento da córnea, sobretudo, em camundongas prenhes. Possivelmente este efeito está relacionado com a redução da produção hormonal de estrogênio e de progesterona.

PURPOSE: To evaluate the morphological changes in murine cornea upon metoclopramide-induced hyperprolactinemia during the proestrous phase or pregnancy. METHODS: Forty adult mice were divided into two groups: (control) CTR1 and (treated with metoclopramide (MET1). After fifty days, half of the mice were sacrificed. The remaining animals were mated, and then labeled as pregnant controls (CTR2). Part of these animals were treated with metoclopramide and constituted the metoclopramide-treated pregnant (MET2) group. The groups CTR2 and MET2 were sacrificed on the 6th day of pregnancy. The hormonal levels were assessed by chemioluminescence and radioimmunoassay methods and the cornea was removed for the histomorphometric study. RESULTS: The epithelial, stromal, endothelial and total thickness in the experimental group was: MET1 and MET2 were higher than one in the control group: CTR1 and CTR2. There was a significant reduction of the hormonal level in the animals that received metoclopramide as compared to controls (CTR1: estradiol = 156.6±42.2 pg/ml; progesterone = 39.4±5.1 ng/ml; prolactin = 130.4±26.2 ng/ml; MET1: estradiol = 108.0±33.1 pg/ml; progesterone = 28.0±6.4 ng/ml; prolactin = 551.5±23.3 ng/ml; CTR2: estradiol = 354.0±56.0 pg/ml; progesterone = 251.0±56.0 ng/ml; prolactin = 423.2±28.1 ng/ml; MET2: estradiol = 293.0±43.0 pg/ml; progesterone = 184.0±33.0 ng/ml; prolactin = 823.1±51.1 ng/ml). CONCLUSION: The metoclopramide-induced hyperprolactinemia may increase corneal layers, mainly in pregnant mice. Possibly, this effect is related to reduction in estrogen and progesterone production.

Effect of simultaneous exposure to lead and cadmium on gonadotropin binding and steroidogenesis on granulosa cells: an in vitro study.

Effects of lead (Pb) and cadmium (Cd) both alone or in combination on the binding of LH and FSH on isolated granulosa cells were studied. Granulosa cells isolated from proestrous rats were incubated (in vitro) with lead acetate and/or cadmium acetate (0.03 microM of Pb or Cd) for 1 hr. LH binding was dropped to 84% in Pb treated cells, 72.5% in Cd treated cells and 74.8% in combined metal treated cells compared to control. FSH binding dropped to 85.5% in Pb treated cells, 71.16% in Cd treated cells and 72.5% in combined metal treated cells compared to control. Activity of 17beta Hydroxy Steroid Dehydrogenase (17betaHSDH), a key steroidogenic enzyme was reduced by 52% in Cd and 37% in combined metal exposed cells whereas Pb exposed cells showed 31% reduction in the enzyme activity. Pretreatment with SH groups protectants (glutathione [GSH], dithiothretol [DTT]) and zinc caused an ameriolation in enzyme activity whereas Zn pretreatment showed an increase in gonadotropin binding in metal exposed cells. These results suggest that both Pb and Cd can cause a reduction in LH and FSH binding, which significantly alters steroid production in vitro and exerts a direct influence on granulosa cell function.

Fluid balance: changes in cycling rats treated with difluoro-methyl-ornithine [DFMO] during the pro-oestrus.

Plasma vesopressin levels have been shown to fluctuate through out the rat oestrus cycle and following ovariectomy. To determine how these fluctuations in vesopressin are related to fluid regulations during the rat oestrus cycle. Studies have been carried out in cycling females rats using a specific inhibitor of Ornithine Decarboxylase [ODC], Di-fluoro-methyl Ornithine [DFMO 20 mg/100g body weight], the animals were housed in individual metabolism cages under 12 hours light/12 hour dark regimen with free access to food and water. Urine samples were collected to determine the osmolality and sodium concentration at 8.00 and 17.00-18.00 hours. The results of this study indicate a significant decrease in urine osmolality and sodium retention in the cycling pro-oestrus rats treated with DFMO as compared to the controls. The result of this study indicates that cause of fluid retention in the cycling rats during pro-oestrus may be the oestradiol dependent increased levels of vesopressin and the increase in the ODC activity in the Magno-cellular neurons is the part of mechanism underlying the oestradiol induced Vesopressin release

Liberación de noradrenalina intramural inducida por soluciones despolarizantes de potasio en utero de rata / Release of intramural noradrenaline induced by depolarizing solutions of potassium in rat uteri

Se estudió la correlación entre la actividad contractil y la liberación de noradrenalina por soluciones de cloruro de potasio (40, 60, 70, 80, 90 y 123mM) en preparaciones de útero de rata a través de las diferentes fases del ciclo estrul, como son el metaestru (M), diestro (D), proestro (P) y estro (E) y útero de rata ovariectomizada (DVX). La respuesta contractil del útero de rata al medio cargado de cloruro de potasio (KCL) depende del estadío endócrino en el que se encuentra. De este modo los úteros de ratas OVX y en las fases M,D,P y E muestran una contracción tóxica al sumergirse en el medio con 40 mM de KCL. Los úteros de ratas OVX y en las fases M y D mostraron una contracción inicial seguida por un relajamiento transitorio, al exponerse a concentraciones de 60, 70, 80, 90, y 123 mM de KCL. En el uretero de ratas en las fases de P y E se disminuyó importantemente el estadío de relajación transitoria al exponerse a soluciones de 60, 70, 80, 90 y 123mM de KCL, presentando solamente contracciones tóxicas. Tiras uterinas de ratas OVX se relajaron significativamente más por KCL de 123 mM que las tiras uterinas en fase de P (0'001). El agregado de propanolol (2D mM) a las tiras uterinas de ratas OVX inhibió la relajación transitoria observada con 123 mM de KCL. 40 mM de KCL no afectaron el eflujo de noradrenalina marcada con tritio (3H-NA) en tiras uterinas de ratas OVX cargadas previamente con transmisor radioactivo. En estas condiciones, se observó que 123 mM de KCL aumentaban el eflujo de 3H-NA. El propanolol (20mM) no afectó la liberación de 3H-NA producida por KCL (123mM) en tiras uterinas de ratas OVX. El estudio presente muestra que los cambios en la contractilidad uterina ante estímulos quirúrgicos durante las diferentes fases del ciclo estral y en ratas OVX podría deberse a la acción de esteroides sexuales a nivel presinóptico al modular la liberación de neurotransmisores