Stress during puberty facilitates precancerous prostate lesions in adult rats

Puberty can be a critical period for the long-term development of diseases, especially for stress-related disorders that depend on neuroendocrine and immune responses. Some organs like the prostate are prone to diseases that result from neuroendocrine or immune challenges, such as cancer. Aim: In the present study, we assessed the long-term effects of an acute pubertal stressor (immune-challenge) on the development of precancerous lesions in adult rats, and compared them with testosterone-induced prostatic lesions. Materials and Methods: Pubertal male rats received a single injection of lipopolysaccharide (LPS) or saline during puberty (5 weeks old). At adulthood (8 weeks old) males were subcutaneously implanted with either an empty capsule or filled with testosterone propionate (100 mg/kg). This resulted in a total of five groups: 1) intact untreated, 2) saline-treated and implanted with a blank capsule, 3) saline-treated and implanted with a testosterone capsule, 4) LPS-treated and implanted with a blank capsule, 5) LPS-treated and implanted with a testosterone capsule. Four weeks later, the rats were sacrified and their prostates processed for histology (hematoxylin and eosin stain) and blood serum processed for hormone analysis (testosterone and corticosterone). Results: Males treated with LPS (stressed during puberty via immune challenge) expressed epithelium dysplasia (specially in the ventral prostate), anisocytosis, presence of mononuclear cells, anisokariosis, non-basal polarity, abnormal nucleus-cytoplasm ratio, proplastic myoepithelium, and granular content in the lumen. These histological alterations were similar, but less severe than those observed in males implanted with testosterone during adulthood. Conclusion: These results indicate that pubertal exposure to an immune challenge (stress) facilitates the long-term development of prostatic lesions in adult male rats

Long-term administration of prolactin or testosterone induced similar precancerous prostate lesions in rats

Evidence indicates that prolactin plays a crucial role in the normal function and development of the prostate, but abnormal high levels of the hormone are associated with hyperplasia and cancer of the gland. Aims: The present study was designed to describe the progressive specific histological abnormalities in the prostate of rats with chronic hyperprolactinemia. Material and Methods: Prolactin was administered during 4; 12 or 24 weeks, and the resulting prostatic alterations were compared with control rats, and also with those treated with testosterone, or the combination of prolactin + testosterone. Results: Rats treated with prolactin, testosterone or prolactin + testosterone expressed precancerous histological abnormalities in the dorsolateral and ventral portions of the prostate as early as in 4 weeks of treatment, but in all cases the malignancy increased after 12 or 24 weeks of treatment. Conclusion: Our study confirms that chronic hyperprolactinemia is a cause of prostate precancerous pathologies. Key Words: prolactin, prostate, cancer, dysplasia, testosterone

Effect of copulation on potentially precancerous prostate lesions, serum testosterone and prolactin levels in rats

The prostate is an exocrine reproductive gland that participates in ejaculation and it is prone to diseases, including cancer. Aim: In the present study, we assessed the long­term effects of copulation on the development of precancerous lesions in rats, and compared them with testosterone­induced prostatic lesions. Materials and Methods: One group of Wistar males was given 10 copulatory sessions to one ejaculation with ovariectomized, hormone­primed females. Sessions occurred twice per week for a total of ten trials. A second group was exposed to females during the same trials, but physical contact was prevented. In addition, each group received a subcutaneous implant in the back either filled with testosterone propionate (T, 100 mg/kg) or empty. This resulted in four subgroups: 1) Control + No sex, 2) Control + Sex, 3) T + No sex and 4) T + Sex. Two days after the 10th trial all the males were sacrificed for prostate histo logy (H&E) and hormone analysis (testosterone and prolactin). Results: Males from the group Control + No sex expressed normal histo logy. However, those in the groups Control + Sex and T + No sex expressed metaplasia and dysplasia in both the dorsolateral and ventral portions of the prostate, respectively. Interestingly, males from the group T + Sex expressed dysplasia in the dorsolateral prostate only, but not in the ventral prostate. Conclusions: These results indicate that constant copulation may facilitate the development of prostatic lesions in males with normal levels of testosterone. However, copulation induces less lesions in the ventral prostate of males treated with testosterone

STRESS DURING PUBERTY FACILITATES PRECANCEROUS PROSTATE LESIONS IN ADULT RATS

Puberty can be a critical period for the long-term development of diseases, especially for stress-related disorders that depend on neuroendocrine and immune responses. Some organs like the prostate are prone to diseases that result from neuroendocrine or immune challenges, such as cancer. Aim: In the present study, we assessed the long-term effects of an acute pubertal stressor (immune-challenge) on the development of precancerous lesions in adult rats, and compared them with testosterone-induced prostatic lesions. Materials and Methods: Pubertal male rats received a single injection of lipopolysaccharide (LPS) or saline during puberty (5 weeks old). At adulthood (8 weeks old) males were subcutaneously implanted with either an empty capsule or filled with testosterone propionate (100 mg/kg). This resulted in a total of five groups: 1) intact untreated, 2) saline-treated and implanted with a blank capsule, 3) saline-treated and implanted with a testosterone capsule, 4) LPS-treated and implanted with a blank capsule, 5) LPS-treated and implanted with a testosterone capsule. Four weeks later, the rats were sacrified and their prostates processed for histology (hematoxylin and eosin stain) and blood serum processed for hormone analysis (testosterone and corticosterone). Results: Males treated with LPS (stressed during puberty via immune challenge) expressed epithelium dysplasia (specially in the ventral prostate), anisocytosis, presence of mononuclear cells, anisokariosis, non-basal polarity, abnormal nucleus-cytoplasm ratio, proplastic myoepithelium, and granular content in the lumen. These histological alterations were similar, but less severe than those observed in males implanted with testosterone during adulthood. Conclusion: These results indicate that pubertal exposure to an immune challenge (stress) facilitates the long-term development of prostatic lesions in adult male rats

Activation of the cerebellum by olfactory stimulation in sexually naive male rats

Introduction: The cerebellum has been linked to multiple functions, such as motor control, cognition, memory, and emotional processing. As for its involvement in the sensory systems, the role of the cerebellum in the sense of smell remains unclear. We suggest that sexually naive male rats will present increased neuronal activity in the cerebellar vermis after being stimulated with almond odour or oestrous odour from receptive females. Methods: We compared activity in the cerebellar vermis using Fos immunoreactivity after olfactory stimulation. Stimulation took place for 60 min in a cube-shaped acrylic chamber with a double bottom. Stimuli were clean woodchip bedding, bedding with almond extract, and bedding taken from a cage of receptive females. Male rats were subsequently anaesthetised with intraperitoneal sodium pentobarbital. Cerebellar tissue was fixed with paraformaldehyde for later immunohistochemical analysis. Results: The number of Fos immunoreactive cells in all lobes of the cerebellar vermis was similar between groups stimulated with almond extract and with oestrous odour, and higher than in the clean woodchip group. Conclusions: Stimulation of the main olfactory system (almond) and the accessory system (oestrous odour) increases Fos protein production in the granular layer of the cortex of the cerebellar vermis in naive male rats. Resumen: Introducción: El cerebelo es una estructura que se ha vinculado con múltiples funciones, tales como control motor, cognición, memoria y procesamiento emocional. En cuanto a su relación con los sistemas sensoriales no está claro el papel que desempeña en relación con el sentido del olfato. Suponemos que las ratas macho sexualmente inexpertas presentarán un incremento en la actividad neuronal del vermis cerebelar tras ser estimuladas con olor de hembra receptiva y almendra. Métodos: Comparamos la actividad de la capa granular del vermis cerebelar mediante la inmunorreactividad a Fos tras estimulación olfativa. Esta estimulación se realizó durante 60 min en cámaras cúbicas de acrílico con un doble fondo. Los estímulos fueron aserrín limpio, con esencia de almendra y proveniente de la cama de hembras receptivas. Finalmente los machos fueron anestesiados con pentobarbital sódico intraperitoneal. El tejido cerebelar fue fijado con paraformaldehído para su posterior análisis inmunohistoquímico. Resultados: El número de células inmunorreactivas a Fos en todos los lóbulos del vermis cerebelar de los grupos estimulados con almendra y hembra receptiva fue similar, pero mayor comparado con el grupo de aserrín limpio. Conclusiones: La estimulación olfativa del sistema olfatorio principal (almendra) y accesorio (hembra receptiva) incrementa la producción de proteína Fos en la capa granular de la corteza cerebelar del vermis de ratas macho sexualmente inexpertas. Keywords: Cerebellum, Fos, Sexual behaviour, Olfactory stimulation, Granular layer, Sexual cues, Palabras clave: Cerebelo, Fos, Conducta sexual, Estimulación olfativa, Capa granular, Señales sexuale

Activación del cerebelo por estimulación olfativa en ratas macho sexualmente inexpertas

Resumen: Introducción: El cerebelo es una estructura que se ha vinculado con múltiples funciones, tales como control motor, cognición, memoria y procesamiento emocional. En cuanto a su relación con los sistemas sensoriales no está claro el papel que desempeña en relación con el sentido del olfato. Suponemos que las ratas macho sexualmente inexpertas presentarán un incremento en la actividad neuronal del vermis cerebelar tras ser estimuladas con olor de hembra receptiva y almendra. Métodos: Comparamos la actividad de la capa granular del vermis cerebelar mediante la inmunorreactividad a Fos tras estimulación olfativa. Esta estimulación se realizó durante 60 min en cámaras cúbicas de acrílico con un doble fondo. Los estímulos fueron aserrín limpio, con esencia de almendra y proveniente de la cama de hembras receptivas. Finalmente los machos fueron anestesiados con pentobarbital sódico intraperitoneal. El tejido cerebelar fue fijado con paraformaldehído para su posterior análisis inmunohistoquímico. Resultados: El número de células inmunorreactivas a Fos en todos los lóbulos del vermis cerebelar de los grupos estimulados con almendra y hembra receptiva fue similar, pero mayor comparado con el grupo de aserrín limpio. Conclusiones: La estimulación olfativa del sistema olfatorio principal (almendra) y accesorio (hembra receptiva) incrementa la producción de proteína Fos en la capa granular de la corteza cerebelar del vermis de ratas macho sexualmente inexpertas. Abstract: Introduction: The cerebellum has been linked to multiple functions, such as motor control, cognition, memory, and emotional processing. As for its involvement in the sensory systems, the role of the cerebellum in the sense of smell remains unclear. We suggest that sexually naive male rats will present increased neuronal activity in the cerebellar vermis after being stimulated with almond odour or oestrous odour from receptive females. Methods: We compared activity in the cerebellar vermis using Fos immunoreactivity after olfactory stimulation. Stimulation took place during 60 min in a cube-shaped acrylic chamber with a double bottom. Stimuli were clean woodchip bedding, bedding with almond extract, and bedding taken from a cage of receptive females. Male rats were subsequently anaesthetised with intraperitoneal sodium pentobarbital. Cerebellar tissue was fixed with paraformaldehyde for later immunohistochemical analysis. Results: The number of Fos immunoreactive cells in all lobes of the cerebellar vermis was similar between groups stimulated with almond extract and with oestrous odour, and higher than in the clean woodchip group. Conclusions: Stimulation of the main olfactory system (almond) and the accessory system (oestrous odour) increases Fos protein production in the granular layer of the cortex of the cerebellar vermis in naive male rats. Palabras clave: Cerebelo, Fos, Conducta sexual, Estimulación olfativa, Capa granular, Señales sexuales, Keywords: Cerebellum, Fos, Sexual behaviour, Olfactory stimulation, Granular layer, Sexual cue

LONG-TERM ADMINISTRATION OF PROLACTIN OR TESTOSTERONE INDUCED SIMILAR PRECANCEROUS PROSTATE LESIONS IN RATS

Evidence indicates that prolactin plays a crucial role in the normal function and development of the prostate, but abnormal high levels of the hormone are associated with hyperplasia and cancer of the gland. Aims: The present study was designed to describe the progressive specific histological abnormalities in the prostate of rats with chronic hyperprolactinemia. Material and Methods: Prolactin was administered during 4; 12 or 24 weeks, and the resulting prostatic alterations were compared with control rats, and also with those treated with testosterone, or the combination of prolactin + testosterone. Results: Rats treated with prolactin, testosterone or prolactin + testosterone expressed precancerous histological abnormalities in the dorsolateral and ventral portions of the prostate as early as in 4 weeks of treatment, but in all cases the malignancy increased after 12 or 24 weeks of treatment. Conclusion: Our study confirms that chronic hyperprolactinemia is a cause of prostate precancerous pathologies. Key Words: prolactin, prostate, cancer, dysplasia, testosterone

Efecto de la lesión electrolítica del estriado dorsomedial sobre la conducta sexual y actividad locomotora de la rata

Resumen: Introducción: Las áreas motoras corticales no solo son influenciadas por aferencias sensitivas periféricas y áreas de asociación prefrontales, sino también por los ganglios basales, específicamente el estriado. El estriado dorsomedial (EDM) y el estriado dorsolateral están involucrados en el aprendizaje espacial y el aprendizaje estímulo-respuesta; sin embargo, cada una de estas zonas pudiera mediar distintos componentes del aprendizaje. El propósito del estudio es determinar el efecto de la lesión electrolítica del EDM sobre el aprendizaje y ejecución de la conducta locomotora y sexual en ratas macho. Método: Una vez que los sujetos aprendieron a ejecutar las pruebas motoras de equilibrio, laberinto, rampa de ascenso y la conducta sexual, se realizó la lesión electrolítica del EDM. Cinco días después se realizaron las pruebas en 2 ocasiones más y se compararon las latencias de ejecución de cada prueba. Resultados: Después de la lesión, los valores promedio de latencia, incrementaron durante la ejecución de las pruebas de laberinto y equilibrio. Sin embargo, los valores promedio en la prueba rampa y conducta sexual, no aportaron efectos contrastantes entre los grupos. Conclusiones: La lesión electrolítica del EDM modifica la ejecución de la actividad locomotora (prueba de laberinto y equilibrio), pero no la ejecución de la conducta sexual. Abstract: Introduction: Cortical motor areas are influenced not only by peripheral sensory afferents and prefrontal association areas, but also by the basal ganglia, specifically the striatum. The dorsomedial striatum (DMS) and dorsolateral striatum are involved in both spatial and stimulus-response learning; however, each of these areas may mediate different components of learning. The aim of the study is to determine the effect of electrolytic lesion to the DMS on the learning and performance of sexual behaviour and locomotor activity in male rats. Method: Once the subjects had learned to perform motor tests of balance, maze navigation, ramp ascent, and sexual behaviour, they underwent electrolytic lesion to the DMS. Five days later, the tests were repeated on 2 occasions and researchers compared performance latencies for each test. Results: Average latency values for performance on the maze and balance tests were higher after the lesion. However, the average values for the ramp test and for sexual behaviour did not differ between groups. Conclusions: Electrolytic lesion of the DMS modifies the performance of locomotor activity (maze test and balance), but not of sexual behaviour. Palabras clave: Estriado dorsomedial, Lesión electrolítica, Conducta sexual, Locomoción, Aprendizaje, Keywords: Dorsomedial striatum, Sexual behaviour, Electrolytic lesion, Locomotion, Learnin

EFFECT OF COPULATION ON POTENTIALLY PRECANCEROUS PROSTATE LESIONS, SERUM TESTOSTERONE AND PROLACTIN LEVELS IN RATS

The prostate is an exocrine reproductive gland that participates in ejaculation and it is prone to diseases, including cancer. Aim: In the present study, we assessed the long­term effects of copulation on the development of precancerous lesions in rats, and compared them with testosterone­induced prostatic lesions. Materials and Methods: One group of Wistar males was given 10 copulatory sessions to one ejaculation with ovariectomized, hormone­primed females. Sessions occurred twice per week for a total of ten trials. A second group was exposed to females during the same trials, but physical contact was prevented. In addition, each group received a subcutaneous implant in the back either filled with testosterone propionate (T, 100 mg/kg) or empty. This resulted in four subgroups: 1) Control + No sex, 2) Control + Sex, 3) T + No sex and 4) T + Sex. Two days after the 10th trial all the males were sacrificed for prostate histo logy (H&E) and hormone analysis (testosterone and prolactin). Results: Males from the group Control + No sex expressed normal histo logy. However, those in the groups Control + Sex and T + No sex expressed metaplasia and dysplasia in both the dorsolateral and ventral portions of the prostate, respectively. Interestingly, males from the group T + Sex expressed dysplasia in the dorsolateral prostate only, but not in the ventral prostate. Conclusions: These results indicate that constant copulation may facilitate the development of prostatic lesions in males with normal levels of testosterone. However, copulation induces less lesions in the ventral prostate of males treated with testosterone