The temporal organization of mammals presents a daily adjustment to the environmental light/dark cycle. The environmental light detected by the retina adjusts the central clock in the suprachiasmatic nuclei, which innervate the pineal gland through a polysynaptic pathway. During the night, this gland produces and releases the nocturnal hormone melatonin, which circulates throughout the whole body and adjusts several bodily functions according to the existence and duration of darkness. We have previously shown that during the time frame of an inflammatory response, pro-inflammatory cytokines, such as tumor necrosis factor-alpha, inhibit while anti-inflammatory mediators, such as glucocorticoids, enhance the synthesis of melatonin, interfering in the daily adjustment of the light/dark cycle. Therefore, injury disconnects the organism from environmental cycling, while recovery restores the light/dark information to the whole organism. Here, we extend these observations by evaluating the effect of a mild restraint stress, which did not induce macroscopic gastric lesions. After 2 h of restraint, there was an increase in circulating corticosterone, indicating activation of the hypothalamus-pituitary-adrenal (HPA) axis. In parallel, an increase in melatonin production was observed. Taking into account the data obtained with models of inflammation and stress, we reinforce the hypothesis that the activity of the pineal gland is modulated by the state of the immune system and the HPA axis, implicating the darkness hormone melatonin as a modulator of defense responses.

This study investigated the effects of perinatal cadmium exposure on physical and reflexologic development of pup rats. It was examined if the immediate postpartum testosterone administration was able to reverse the toxic effects of the metal. Forty Wistar pregnant rats were divided into three groups: control and 10 and 20 mg kg(-1) per day of cadmium chloride. These dams were treated from gestational days 18 to 21, and until the 7th lactation day. Immediately after birth, half of the offspring from the experimental and control groups received 50 microL of testosterone 0.2% i.p. The maternal body weight gain, food and water consumption were measured during the treatment period. In pups, the body weight, body length, physical landmarks, reflex development and the general activity were assessed. Results showed that: only 20 mg kg(-1) cadmium induced maternal toxicity; pup body weight and body weight gain were reduced in all experimental groups; only the cadmium-exposed offspring not treated with testosterone treatment showed a reduction in body length and body length gain; cadmium highest dose reduced the anogenital index in pups and delayed physical and reflexes development; and cadmium effects on the offspring, except in body length gain, were not reversed by testosterone. The results indicate that perinatal maternal exposure to cadmium promoted changes in the development of male rat offspring, reprogramming the pup's development. Testosterone administration was not able to reverse the cadmium effects, even on those parameters more directly related to the androgenic system as the testis descent and anogenital distance delays.

This study investigated the effects of perinatal cadmium exposure on sexual behavior, organ weight, and testosterone levels in adult rats. We examined whether immediate postpartum testosterone administration is able to reverse the toxic effects of the metal. Forty pregnant Wistar rats were divided into three groups: 1) control, 2) 10 mg kg -1 cadmium chloride per day, and 3) 20 mg kg -1 cadmium chloride per day. These dams were treated on gestational days 18 and 21 and from lactation 1 to 7. Immediately after birth, half of the offspring from the experimental and control groups received 50 µl (i.p.) of 0.2% testosterone. Male sexual behavior, histological analysis and weight of organs as well as serum testosterone levels were assessed. Results showed that both cadmium doses disrupted sexual behavior in male rats, and postnatal treatment with testosterone reversed the toxic effects of 10 mg kg -1 cadmium and attenuated the effects of 20 mg kg -1 cadmium. Body weight and absolute testis, epididymis, and seminal vesicle weight were decreased by the higher cadmium dose, and testosterone supplementation did not reverse these effects. Serum testosterone levels were unaffected by both cadmium doses. No histological changes were detected in all organs analyzed. Maternal cadmium exposure effects in sexual parameters of male rat offspring were explained by the altered masculinization of the hypothalamus. We suggest that cadmium damaged cerebral sexual differentiation by its actions as an endocrine disruptor and supported by the changes discretely observed from early life during sexual development to adult life, reflected by sexual behavior. Testosterone supplementation after birth reversed some crucial parameters directly related to sexual behavior.