Melatonin supplementation decreases prolactin synthesis and release in rat adenohypophysis: correlation with anterior pituitary redox state and circadian clock mechanisms.

In the laboratory rat, a number of physiological parameters display seasonal changes even under constant conditions of temperature, lighting, and food availability. Since there is evidence that prolactin (PRL) is, among the endocrine signals, a major mediator of seasonal adaptations, the authors aimed to examine whether melatonin administration in drinking water resembling in length the exposure to a winter photoperiod could affect accordingly the 24-h pattern of PRL synthesis and release and some of their anterior pituitary redox state and circadian clock modulatory mechanisms. Melatonin (3 µg/mL drinking water) or vehicle was given for 1 mo, and rats were euthanized at six time intervals during a 24-h cycle. High concentrations of melatonin (>2000 pg/mL) were detected in melatonin-treated rats from beginning of scotophase (at 21:00 h) to early photophase (at 09:00 h) as compared with a considerably narrower high-melatonin phase observed in controls. By cosinor analysis, melatonin-treated rats had significantly decreased MESOR (24-h time-series average) values of anterior pituitary PRL gene expression and circulating PRL, with acrophases (peak time) located in the middle of the scotophase, as in the control group. Melatonin treatment disrupted the 24-h pattern of anterior pituitary gene expression of nitric oxide synthase (NOS)-1 and -2, heme oxygenase-1 and -2, glutathione peroxidase, glutathione reductase, Cu/Zn- and Mn-superoxide dismutase, and catalase by shifting their acrophases to early/middle scotophase or amplifying the maxima. Only the inhibitory effect of melatonin on pituitary NOS-2 gene expression correlated temporally with inhibition of PRL production. Gene expression of metallothionein-1 and -3 showed maxima at early/middle photophase after melatonin treatment. The 24-h pattern of anterior pituitary lipid peroxidation did not vary after treatment. In vehicle-treated rats, Clock and Bmal1 expression peaked in the anterior pituitary at middle scotophase, whereas that of Per1 and Per2 and of Cry1 and Cry2 peaked at the middle and late photophase, respectively. Treatment with melatonin raised mean expression of anterior pituitary Per2, Cry1, and Cry2. In the case of Per1, decreased MESOR was observed, although the single significant difference found between the experimental groups when analyzed at individual time intervals was increase at early scotophase in the anterior pituitary of melatonin-treated rats. Melatonin significantly phase-delayed expression of Per1, Per2, and Cry1, also phase-delayed the plasma corticosterone circadian rhythm, and increased the amplitude of plasma corticosterone and thyrotropin rhythms. The results indicate that under prolonged duration of a daily melatonin signal, rat anterior pituitary PRL synthesis and release are depressed, together with significant changes in the redox and circadian mechanisms controlling them.

Continuous versus discontinuous drinking of an ethanol liquid diet in peripubertal rats: effect on 24-h variation of lymph node and splenic mitogenic responses and lymphocyte subset populations.

Excessive alcohol consumption continues to be a major public health problem, particularly in the adolescent and young adult populations. Generally, such a behavior tends to be confined to the weekends, to attain frequently binge drinking. This study in peripubertal male rats compares the effect of the discontinuous feeding of a liquid diet containing a moderate amount of ethanol (6.2% wt/vol) to that of continuous ethanol administration or a control diet, taking as end points the 24-h variations of plasma prolactin levels and mitogenic responses and lymphocyte subset populations in submaxillary lymph nodes and spleen. Animals received the ethanol liquid diet starting on day 35 of life, the diet being similar to that given to controls except for that maltose was isocalorically replaced by ethanol. Ethanol provided 36% of the total caloric content. Every week, the discontinuous ethanol group received the ethanol diet for 3 days and the control liquid diet for the remaining 4 days. After 4 weeks, rats were killed at six time intervals, beginning at 0900 h. A significant decrease of splenic cells' response to concanavalin A, and of lymph node and splenic cells' response to lipopolysaccharide was found in rats under the discontinuous ethanol regime, when compared with control- or ethanol-chronic rats. Under discontinuous ethanol feeding, mean values of lymph node and splenic CD8(+) and CD4(+)-CD8(+) cells decreased, whereas those of lymph node and splenic T cells, and splenic B cells, augmented. In rats chronically fed with ethanol, splenic mean levels of CD8(+) and CD4(+)-CD8(+) cells augmented. Both modalities of ethanol administration disrupted the 24 h variation in immune function seen in controls. Mean plasma prolactin levels increased by 3.6-fold and 8.5-fold in rats chronically or discontinuously fed with alcohol, respectively. The immune parameters examined in an additional group of rats fed regular chow and water ad libitum did not differ significantly from control liquid diet. The results support the view that the discontinuous drinking of a moderate amount of ethanol can be more harmful for the immune system than a continuous ethanol intake, presumably by inducing a greater stress as indicated by the augmented plasma prolactin levels observed.