N. Márquez

Pubertal and postpubertal cadmium exposure differentially affects the hypothalamic–pituitary–testicular axis function in the rat

The effects of administration of cadmium on levels of hormones along the hypothalamic-pituitary-testicular axis were studied in rats. Male rats were treated subcutaneously from days 30 to 60 (pubertal rats) or from days 60 to 90 of life (postpubertal rats), with cadmium chloride (CdCl2) at a dose of 0.5 or 1 mg/kg, every 4 days in an alternate schedule, starting from the lower dose. Age-matched control rats received 0.3 m of saline subcutaneously every 4 days. The levels of norepinephrine (NE) increased on cadmium exposure in pubertal rats in all hypothalamic areas studied, but decreased in the median eminence. In contrast, in postpubertal rats the levels of NE only did not decrease in the posterior hypothalamus. Serotonin (5-HT) concentration in pubertal and postpubertal rats decreased in all hypothalamic regions, while serotonin turnover (measured by the ratio 5-hydroxyindolacetic acid/serotonin [5-HIAA/5-HT]) increased in the anterior hypothalamus. The serotonin metabolism was also increased in the median eminence in the pubertal and in the posterior hypothalamus in the postpubertal rats. Plasma levels of luteinizing hormone (LH) were not modified by cadmium in both age groups, but follicle stimulating hormone (FSH) levels decreased in postpubertal rats, but was not altered in pubertal rats. Plasma levels of testosterone increased in pubertal rats but decreased in postpubertal rats. Cadmium accumulation increased in the hypothalamus and testes in all the cadmium-treated animals, whereas in the pituitary accumulation of cadmium was found only in postpubertal rats. These data suggest that cadmium exerts age-dependent effects on the hypothalamic-pituitary-testicular axis function, and a disruption of the regulatory mechanisms of the hypothalamic-pituitary-gonadal axis emerges.

Cadmium effects on hypothalamic-pituitary-testicular axis in male rats.

This study analyzes cadmium effects at the hypothalamic-pituitary-testicular axis. Male rats were given cadmium during puberty or adulthood. Cadmium exposure through puberty increased norepinephrine content in all hypothalamic areas studied, but not in the median eminence. Metal exposure increased serotonin turnover in median eminence and the anterior hypothalamus, while decreased it in mediobasal hypothalamus. Also, decreased plasma levels of testosterone were found. Cadmium exposure during adulthood increased norepinephrine content in posterior hypothalamus and decreased the neurotransmitter content in anterior and mediobasal hypothalamus. Decreased circulating levels of luteinizing hormone (LH) and testosterone and increased plasma follicle stimulating hormone (FSH) levels were also observed. Cadmium accumulated in all analyzed tissues. Various parameters showed age-dependent changes. These data suggest that cadmium globally effects hypothalamic-pituitary-testicular axis function by acting at the three levels analyzed and that an interaction between cadmium exposure and age emerge.

Cadmium affects the episodic luteinizing hormone secretion in male rats: possible age-dependent effects.

Cadmium affects luteinizing hormone (LH) secretion through unknown mechanisms. The present study was undertaken to assess whether chronic exposure to low concentrations of cadmium may affect the episodic secretion of LH and if these effects are age-dependent. Male rats were given cadmium at a dose of 50 ppm in the drinking water, from day 30 to 60 or from day 60 to 90 of life. Age-matched rats with access to cadmium-free water were used as controls. At the end of the treatment, blood samples were collected every 7 min for 3 h, from 10:30 to 13.30 in conscious, freely moving rats. In control animals, mean serum LH levels and pulse duration increased with age (P < or = 0.001), and pulse frequency and the relative amplitude of LH pulses decreased (P < or = 0.001). Cadmium administration, from day 30 to 60 of life, decreased the pulse frequency and mean half-life of the hormone (P < or = 0.05, P < or = 0.01, respectively). However, no changes in any other parameters studied were observed as compared to the control group. When cadmium was administered from day 60 to 90, mean serum LH levels and the duration of LH pulses decreased (P < or = 0.05), whereas the pulse frequency increased (P < or = 0.05). The absolute and relative amplitude of the LH peaks and the mean half-life of the hormone were not changed after cadmium administration from day 60 to 90. These results indicate that low doses of cadmium change the pulsatile secretion of LH in male rats and that the effect of cadmium on episodic LH release was age-dependent.

Cadmium effects on dopamine turnover and plasma levels of prolactin, GH and ACTH

This paper analyzes possible dopamine (DA) mediated cadmium effects on plasma levels of prolactin, growing hormone (GH) and adrenocorticotropic hormone (ACTH), and if these changes are related to metal accumulation. For that purpose, adult male rats were treated with 50 mg/L of CdCl2 in the drinking water for one month. Plasma levels of prolactin, ACTH and GH were measured by specific double antibody radioimmunoassays. DA was measured by high performance liquid chromatography using electrochemical detection. Cadmium content in the tissues was measured by atomic absorption spectometry with graphite furnace. Analysis was performed by using a T-Student test. Metal exposure increased DA content (34.79±3.06vs. 18.2±2.88 pg/mg protein) and decreased its turnover (0.40±0.07vs. 0.75±0.06) in posterior hypothalamus. Cadmium also decreased DA turnover in median eminence (0.48±0.15vs. 1.50±0.63). Plasma levels of prolactin and GH decreased (2.4±0.11vs. 3.1±0.15 ng/mL and 5.37±0.05vs. 9.87±1.8 ng/mL respectively), while those of ACTH increased (2.73±0.14vs. 1.7±0.16 ng/mL). Cadmium concentration increased in both hypothalamus (4.88±0.34vs. 0.72±0.2 μg/g) and pituitary (22.82±4.57vs. 5.02±1.25 μg/g) after the metal exposure. These results suggest that cadmium effects on the secretion of these hormones are not mediated by dopamine and might be correlated to the metal accumulation at pituitary level.ResumenSe estudia el posible efecto del cadmio sobre los niveles plasmáticos de prolactina, hormona del crecimiento (GH) y adrenocorticotropina (ACTH) mediados por la dopamina (DA), y si los cambios están relacionados con la acumulación del metal. Para ello, se han tratado ratas macho adultas con 50 mg/L de CdCl2 en el agua de bebida durante un mes. Las hormonas se miden por radioinmunoanálisis específicos. La DA y su metabolito DOPAC se miden por cromatografia líquida de alta resolución. El contenido de cadmio en el hipotálamo y la hipófisis se mide mediante cromatografía de absorción atómica con cámara de grafito. La exposición al metal aumenta el contenido de DA (34,79±3,06vs. 18,2±2.88 pg/mg proteina) y disminuye su tasa de recambio (0,40±0,07vs. 0,75±0,06) en el hipotálamo posterior. También disminuye la tasa de recambio de DA en la eminencia media (0,48±0,15vs. 1,50±0,63). Los niveles plasmáticos de prolactina y GH disminuyen (2,4±0,11vs. 3,1±0,15 ng/mL y 5,37±0,05vs. 9,87±1,8 ng/mL, respectivamente), mientras que aumentan los de ACTH (2,73±0,14vs. 1,7±0,16 ng/mL). La concentración de cadmio aumenta en el hipotálamo (4,88±0,34vs. 0,72±0,2 μg/g) e hipófisis (22,82±4,57vs. 5,02±1,25 μg/g) tras la exposición al metal. Estos resultados sugieren que los efectos del cadmio sobre la secreción de estas hormonas no son a través de la dopamina, aunque se correlacionan con la acumulación del metal a nivel hipofisario.

Pubertal dependent effects of cadmium on episodic prolactin secretion in male rats.

Abstract This work was undertaken to assess if exposure to cadmium related to puberty may affect the episodic pattern of prolactin. Male rats were submitted to cadmium exposure, from day 30 to 60 or from day 60 to 90 of life respectively, at a dose of 50 ppm in the drinking water. Control age-matched rats received cadmium-free water. Prepubertal cadmium administration decreased mean serum prolactin levels and the absolute amplitude of the prolactin pulses. Subchronic exposure to cadmium of adult rats decreased mean serum prolactin levels, the absolute amplitude of the prolactin pulses and their duration, and the mean half-life of the hormone. These results suggest that subchronic cadmium exposure changes the secretory pattern of prolactin in adult male rats in a puberty-dependent way.

Oral cadmium exposure throughout puberty does not inhibit secretion of prolactin, GH and ACTH through dopamine metabolism changes in male rat.

This work analyzed possible dopamine-mediated cadmium effects on plasma prolactin, GH and ACTH levels and if these changes were related to metal accumulation. Male rats were treated from day 30 to 60 of life with 50 mg/L of CdCl2 in the drinking water. Cadmium exposure decreased the dopamine (DA) metabolism (DOPAC/DA ratio) in all brain areas studied, and plasma levels of prolactin, GH and ACTH were diminished. The cadmium concentration did not increase nor in hypothalamus nor in the pituitary after the metal exposure. These results suggest that cadmium inhibits the secretion of these pituitary hormones and this inhibitory effect is not mediated by dopamine or the degree of metal accumulation.