ABSTRACT
Recently, it has become clear that many of the intracellular signals mediated by Ang II receptors are similar to the signaling pathways activated by receptor tyrosine kinases. In the present paper, we are reporting a full characterization of Ang II receptors in rat fetal membranes. We assayed binding of the Ang II antagonist [125I]Sar1Ile8Ang II and the AT2 specific competitor [(125)1]CGP42112. Both ligands exhibited a rapid equilibrium and a high specificity for Ang II receptors. Competition studies confirmed the presence of both receptor subtypes, with a predominance of AT2 receptors and the following order of potency: CGP42112>Ang II>Losartan>PD123177. Immunoblotting studies of tyrosine phosphoproteins showed that Ang II (10(-6)M) mediates a rapid reduction in tyrosine phosphorylation of several proteins with apparent molecular masses in the range of 30-45 kDa. Increasing concentrations of Ang II (10(-9) - 10(-6)M) showed a dose-response behavior, suggesting a clear physiological role of the observed effect. The response, blocked by Losartan and PD123177, seems to be mediated by both receptor subtypes. These results clearly indicate that both Ang II receptors mediate tyrosine dephosphorylation in early stages of development and support a role of these receptors in growth and development.
Subject(s)
Receptors, Angiotensin/metabolism , Tyrosine/metabolism , 1-Sarcosine-8-Isoleucine Angiotensin II/analogs & derivatives , 1-Sarcosine-8-Isoleucine Angiotensin II/metabolism , Angiotensin-Converting Enzyme Inhibitors , Animals , Binding, Competitive , Female , Iodine Radioisotopes , Kinetics , Phosphorylation , Rats , Rats, Inbred WKY , Receptor, Angiotensin, Type 2ABSTRACT
Considering that the vizcacha (Lagostomus maximus maximus) is a very Lithium sensitive rodent, we planned a biochemical-histological study injecting IP doses of 1 mEq/kg/day LiCl during one month to adult vizcachas, and they were divided into three lots: Lot I the optical microscopy revealed evident renal, gonadal, hyphophyseal and adrenal damages; the biochemical analysis showed that Li significantly decreased the female serum LH levels while testosterone and estradiol levels were not affected. The male Li serum values resulted to be significantly higher than those of female animals. The damage was greater in male specimens. Lott II: the tissue recovery from the damage observed in Lot I was the following: total in hyphophysis, partial in testis, the same in kidney and was enhanced in adrenal and ovary. The Li renal clearance was determined in Lot III verifying no changes in both sexs. According to our results, Li (1 mEq/kg/day during one month) produce modifications in different tissues probably the gonadal damage may be consequence of a direct Li effect and not for a hyphophysis alteration, since in male vizcacha the LH serum level was not changed. In regard to the selective effect in the suprarenal glomerulus structure, this Li effect is produced via hyphophysis. In conclusion, the selective effect of Li on adrenal and gonada organs of this rodent is a contribution in order to warm about the possible reproduction of such effects in human beings.
Subject(s)
Adrenal Glands/drug effects , Gonads/drug effects , Lithium Chloride/pharmacology , Luteinizing Hormone/blood , Rodentia/blood , Adrenal Glands/pathology , Animals , Female , Gonads/pathology , Kidney Cortex/pathology , Lithium Chloride/blood , Male , Pituitary Gland/pathology , Sex FactorsABSTRACT
Considerando que la vizcacha (lagostomus maximus maximus) es un roedor muy sensible al Litio (Li), planificamos un estudio bioquímico-histológico inyectando cloruro de Li 1 mEq/Kg/día vía intraperitoneal durante un mes a vizcachas adultas de ambos sexos agrupadas en tres lotes. En el lote I se comprobó por técnicas de microscopía óptica un evidente dano renal, gonodal, hipofisario y adrenal; por métodos bioquímicos se comprobó que el Li disminuyó significativamente los niveles séricos de LH en hembra, el contenido de testosterona y estradiol no fue modificado. En machos el Li sérico resultó significativamente mayor (p<0.01, Prueba de t) que en hembras. El dano fue mayor en machos. en el Lote II se estudió a 30 días de la última administración el grado de recuperación tisular del dano comprobado en el Lote I. Se verificó una recuperación total en hipófisis, parcial en testículo, nula en rinón y se incrementó el dano en adrenal y ovario. Con respecto al efecto seletivo sobre la zona glomerulosa adrenal del Li sería producido via hipófisis. En conclusión el efecto selectivo de Li en adrenal y gónadas en este roedor es una contribución para alertar sobre la posible producción de estos efectos en humanos (AU)
Subject(s)
Animals , Male , Female , Lithium Chloride/pharmacology , Adrenal Glands/drug effects , Gonads/drug effects , Luteinizing Hormone/blood , Lithium Chloride/blood , Adrenal Glands/pathology , Gonads/pathology , Pituitary Gland/pathology , Kidney Cortex/pathology , Sex Factors , RodentiaABSTRACT
Considering that the vizcacha (Lagostomus maximus maximus) is a very Lithium sensitive rodent, we planned a biochemical-histological study injecting IP doses of 1 mEq/kg/day LiCl during one month to adult vizcachas, and they were divided into three lots: Lot I the optical microscopy revealed evident renal, gonadal, hyphophyseal and adrenal damages; the biochemical analysis showed that Li significantly decreased the female serum LH levels while testosterone and estradiol levels were not affected. The male Li serum values resulted to be significantly higher than those of female animals. The damage was greater in male specimens. Lott II: the tissue recovery from the damage observed in Lot I was the following: total in hyphophysis, partial in testis, the same in kidney and was enhanced in adrenal and ovary. The Li renal clearance was determined in Lot III verifying no changes in both sexs. According to our results, Li (1 mEq/kg/day during one month) produce modifications in different tissues probably the gonadal damage may be consequence of a direct Li effect and not for a hyphophysis alteration, since in male vizcacha the LH serum level was not changed. In regard to the selective effect in the suprarenal glomerulus structure, this Li effect is produced via hyphophysis. In conclusion, the selective effect of Li on adrenal and gonada organs of this rodent is a contribution in order to warm about the possible reproduction of such effects in human beings.
ABSTRACT
Considerando que la vizcacha (lagostomus maximus maximus) es un roedor muy sensible al Litio (Li), planificamos un estudio bioquímico-histológico inyectando cloruro de Li 1 mEq/Kg/día vía intraperitoneal durante un mes a vizcachas adultas de ambos sexos agrupadas en tres lotes. En el lote I se comprobó por técnicas de microscopía óptica un evidente dano renal, gonodal, hipofisario y adrenal; por métodos bioquímicos se comprobó que el Li disminuyó significativamente los niveles séricos de LH en hembra, el contenido de testosterona y estradiol no fue modificado. En machos el Li sérico resultó significativamente mayor (p<0.01, Prueba de t) que en hembras. El dano fue mayor en machos. en el Lote II se estudió a 30 días de la última administración el grado de recuperación tisular del dano comprobado en el Lote I. Se verificó una recuperación total en hipófisis, parcial en testículo, nula en rinón y se incrementó el dano en adrenal y ovario. Con respecto al efecto seletivo sobre la zona glomerulosa adrenal del Li sería producido via hipófisis. En conclusión el efecto selectivo de Li en adrenal y gónadas en este roedor es una contribución para alertar sobre la posible producción de estos efectos en humanos
Subject(s)
Animals , Male , Female , Adrenal Glands/drug effects , Lithium Chloride/pharmacology , Gonads , Luteinizing Hormone/blood , Adrenal Glands/pathology , Lithium Chloride/blood , Kidney Cortex/pathology , Pituitary Gland/pathology , Gonads/pathology , Rodentia , Sex FactorsABSTRACT
Seasonal changes in the reproductive activity of the adult male vizcacha (Lagostomus maximus maximus), a South American rodent, were investigated. Monthly, for 1 year, the animals were captured during the night near their burrows in the vicinity of San Luis, Argentina. The animals were killed, and samples of blood and the testes were collected. The testosterone serum levels were determined and the testicular tissue was used for biochemical and structural studies. Significant changes associated with seasonal cycles were found. In July-August (winter in South America), a short hibernal period of sexual quiescence, decline in testicular volume, and a significant decrease in serum testosterone were observed. The in vitro testosterone production and testicular LH, FSH, and PRL receptors revealed a significant decrease during this period. During September-November (spring season), recovery was observed, with a significant increase in gonadal activity during April-May (autumn season). During this season, the gonadal volume was increased, the serum testosterone and the in vitro stimulation of testosterone production by hCG (as well as the basal levels) also revealed a significant increase. Correspondingly, the concentration of testicular LH, FSH, and PRL receptors was elevated. These results indicate an increase in parameters related to testicular function. A gradual reduction in the testicular activity was observed in June-July (early winter). Our findings indicate that the male adult vizcacha, under natural conditions, exhibits characteristics of an annual reproductive cycle.
Subject(s)
Receptors, Cell Surface/metabolism , Rodentia/physiology , Testis/metabolism , Testosterone/blood , Animals , Hemolysis , Leydig Cells/physiology , Male , Receptors, FSH/metabolism , Receptors, LH/metabolism , Receptors, Prolactin/metabolism , Seasons , Testis/anatomy & histology , Testosterone/biosynthesisABSTRACT
Seasonal changes in reproductive activity in the adult male vizcacha (Lagostomus maximus maximus), a South American rodent, were investigated. Monthly, for 2 yr, the animals were killed and decapitated during the night near their burrows in the vicinity of San Luis, Argentina. The testes, epididymides, and pineal glands were removed and used for biochemical and structural studies. Significant changes associated with seasonal cycles were found. 1) In July-August (winter in South America), a short hibernal period of sexual quiescence, decline in testicular and epididymal weights, arrest of spermatogenesis, and decrease of serum testosterone were observed. The gonads regressed during this period, with regression most pronounced in August. 2) During September-November (spring), a recovery period--without arrest of spermatogenesis--was observed, with significant expression of gonadal activity during April-May (autumn). In this season, gonadal weight was increased and spermatogenesis was complete. These results indicate an increase in sexual activity as well as in the ability to secrete testosterone. A gradual reduction of testicular activity appeared in June-July (early winter). Conversely, in this period, the pineal hydroxyindole-O-methyl transferase activity decreased in contrast to the highest values observed in winter. Our findings indicate that the male adult vizcacha under natural conditions exhibits an annual reproductive cycle. A possible relationship between increased pineal activity and gonadal regression is also suggested.
