Melatonin expression in periodontitis and obesity: An experimental in-vivo investigation.

BACKGROUND AND OBJECTIVE: Melatonin deficiency has been associated with obesity and systemic inflammation. This study aims to evaluate whether melatonin could interfere with the mechanisms of co-morbidity linking obesity and periodontitis. MATERIAL AND METHODS: Twenty-eight male Wistar rats were randomly divided in 4 groups: control group (Con) (fed with standard diet); high-fat diet group (HFD) (fed with a diet containing 35.2% fat); Con group with induced periodontitis (Con-Perio) and HFD group with induced periodontitis (HFD-Perio). To induce periodontitis, the method of oral gavages with Porphyromonas gingivalis ATCC W83K1 and Fusobacterium nucleatum DMSZ 20482 was used. Circulating melatonin levels were analyzed by multiplex immunoassays. Periodontitis was assessed by alveolar bone loss (micro-computed tomography and histology) and by surrogate inflammatory outcomes (periodontal pocket depth, modified gingival index and plaque dental index). RESULTS: Plasma melatonin levels were significantly decreased (P < .05) in the obese rats with periodontitis when compared with controls or with either obese or periodontitis rats. Alveolar bone loss increased 27.71% (2.28 µm) in HFD-Perio group compared with the Con group. The histological analysis showed marked periodontal tissue destruction with osteoclast activity, particularly in the HFD-Perio group. A significant negative correlation (P < .05) was found between periodontal pocket depth, modified gingival index and circulating melatonin levels. CONCLUSION: Obese and periodontitis demonstrated significantly lower melatonin concentrations when compared with controls, but in obese rats with periodontitis these concentrations were even significantly lower when compared with either periodontitis or obese rats. These results may indicate that melatonin deficiency could be a key mechanism explaining the co-morbidity effect in the association between obesity and periodontitis.

In vitro seasonal variations of LH, FSH and prolactin secretion of the male rat are dependent on the maternal pineal gland.

The maternal pineal gland is involved in the seasonal rhythms entrainment. We evaluate the effect of maternal pinealectomy (PIN-X), also melatonin replacement (PIN-X+MEL) during pregnancy on "in vitro" gonadotropins and prolactin seasonal variations. Male offspring from control, PIN-X and PIN-X+MEL mother Wistar rats were studied at 31 and 60 days of age. In vitro LH release from controls was season-dependent during prepubertal and pubertal periods showing reduced values in winter. The mother pineal gland seems to be important in the entrainment of seasonal variations of in vitro pituitary LH release, since altered secretion showing very high values was observed in summer. Melatonin treatment to PIN-X mothers partially restored the LH response. The effect of pinealectomy upon LH secretion disappears at the pubertal phase. A different pattern was observed for FSH release, without seasonal variations at 31 or at 60 days of age in control offspring, but pinealectomy to mothers or melatonin treatment resulted in seasonal variations. Seasonal influence was also observed in the prolactin pituitary release of controls. PIN-X mother offspring showed delayed seasonal variations at 31 and 60 days of age. The effect of maternal melatonin treatment during pregnancy was observed up to 60 days of age.

Cadmium exposure disrupts GABA and taurine regulation of prolactin secretion in adult male rats.

This work was undertaken to evaluate the possible effects of cadmium exposure on 24 h changes of gamma-aminobutyric acid (GABA) and taurine median eminence and pituitary contents. Also the possible alterations of the regulatory mechanisms of GABA and taurine on prolactin secretion were evaluated. Adult male rats were given cadmium at a dose of 25 mg/l of cadmium chloride in the drinking water for 30 days. Control age-matched rats received cadmium free water. Metal exposure induced the appearance of a maximal value of prolactin at 08:00 h. In median eminence, cadmium abolished the GABA and taurine maximal values and decreased GABA and taurine mean levels. In the anterior pituitary, cadmium treatment phase advanced 12 h the peak observed in controls at 00:00 h for both amino acids. There was a positive correlation between GABA and taurine contents in median eminence and the anterior pituitary in both control and cadmium-exposed animals. However, the correlation between GABA or/and taurine with prolactin levels disappeared in cadmium-exposed animals. These results suggest that cadmium exposure affects GABA and taurine daily pattern in the median eminence and anterior pituitary, and those changes explain, at least in part, the modification in the regulatory pattern of prolactin secretion.

Toxic effects of methoxychlor administered subcutaneously on the hypothalamic-pituitary-testicular axis in adult rats.

This study was undertaken to evaluate the effects of methoxychlor MTX at the hypothalamic-pituitary-testicular axis in adult male rats. This global objective comprises three major aims: (1) to analyze the possible differential MTX effects in norepinephrine and serotonin concentration an in serotoninergic metabolism in anterior, mediobasal and posterior hypothalamus and median eminence; (2) to evaluate effects induced by MTX exposure on gonadotropins and testosterone; 93 to elucidate whether the regulatory interactions in the hypothalamic-pituitary-testicular axis are modified by this pesticide. Animals were administered subcutaneously 25mg/kg/day of MTX for 1 month. MTX increased norepinephrine and serotonin content in anterior hypothalamus (P < or = 0.05), but decreased serotonin concentration in posterior hypothalamus (P < or = 0.05). MTX diminished serotonin turnover in anterior hypothalamus (P < or = 0.01) and decreased plasma LH (P < or = 0.001) and testosterone (P < or = 0.05) levels but those of FSH remained unmodified. We can conclude that MTX exposure: (1) could exert differential effects in norepinephrine and serotonin concentration an in serotoninergic metabolism in anterior, mediobasal and posterior hypothalamus and median eminence, being the anterior hypothalamus the most sensitive region to the pesticide; (2) could inhibit LH and testosterone secretion without changing FSH; (3) four potential pathways might be involved in MTX effects on testosterone secretion (changing LH secretion; modifying serotonin and norepinephrine at the hypothalamic level; alterating the direct neural pathway between brain and testes; and/or by a direct effect in testes).

Melatonin, environmental light, and breast cancer.

Although many factors have been suggested as causes for breast cancer, the increased incidence of the disease seen in women working in night shifts led to the hypothesis that the suppression of melatonin by light or melatonin deficiency plays a major role in cancer development. Studies on the 7,12-dimethylbenz[a]anthracene and N-methyl-N-nitrosourea experimental models of human breast cancer indicate that melatonin is effective in reducing cancer development. In vitro studies in MCF-7 human breast cancer cell line have shown that melatonin exerts its anticarcinogenic actions through a variety of mechanisms, and that it is most effective in estrogen receptor (ER) alpha-positive breast cancer cells. Melatonin suppresses ER gene, modulates several estrogen dependent regulatory proteins and pro-oncogenes, inhibits cell proliferation, and impairs the metastatic capacity of MCF-7 human breast cancer cells. The anticarcinogenic action on MCF-7 cells has been demonstrated at the physiological concentrations of melatonin attained at night, suggesting thereby that melatonin acts like an endogenous antiestrogen. Melatonin also decreases the formation of estrogens from androgens via aromatase inhibition. Circulating melatonin levels are abnormally low in ER-positive breast cancer patients thereby supporting the melatonin hypothesis for breast cancer in shift working women. It has been postulated that enhanced endogenous melatonin secretion is responsible for the beneficial effects of meditation as a form of psychosocial intervention that helps breast cancer patients.

Toxic effects of methoxychlor in rat striatum: modifications in several neurotransmitters.

Neurotoxic effects of methoxychlor (MTX) are poorly understood at present. This study was undertaken to evaluate the possible effects of MTX in norepinephrine, dopamine and amino acid contents and serotonin turnover in rat striatum. For this purpose, adult male Sprague-Dawley rats were administered 25 mg/kg/day of MTX in sesame oil or vehicle only for 30 days. The neurotransmitters of interest were measured in the striatum by HPLC. MTX decreased norepinephrine and 5-hydroxyindole acetic acid (5-HIAA) content and serotonin turnover (measured as 5-HIAA/serotonin ratio), and increased glutamate and GABA concentrations. However, the content of serotonin, aspartate, glutamine and taurine was not modified by MTX exposure. These data suggest that MTX exposure inhibits norepinephrine synthesis and serotonin metabolism. The inhibitory effect on norepinephrine could be explained, at least in part, by the increase of both GABA and glutamate contents. Further studies are needed to understand the effects of MTX on serotonin. Also a disruptive effect of MTX on the metabolisms of glutamate, aspartate, glutamine and GABA emerges.

Toxic effects of methoxychlor in rat striatum: modifications in several neurotransmitters

Neurotoxic effects of methoxychlor (MTX) are poorly understood at present.This study was undertaken to evaluate the possible effects of MTX in norepinephrine,dopamine and amino acid contents and serotonin turnover in rat striatum. Forthis purpose, adult male Sprague-Dawley rats were administered 25 mg/kg/day ofMTX in sesame oil or vehicle only for 30 days. The neurotransmitters of interestwere measured in the striatum by HPLC. MTX decreased norepinephrine and 5-hydroxyindole acetic acid (5-HIAA) content and serotonin turnover (measured as 5-HIAA/serotonin ratio), and increased glutamate and GABA concentrations. However,the content of serotonin, aspartate, glutamine and taurine was not modified byMTX exposure. These data suggest that MTX exposure inhibits norepinephrine synthesisand serotonin metabolism. The inhibitory effect on norepinephrine could beexplained, at least in part, by the increase of both GABA and glutamate contents.Further studies are needed to understand the effects of MTX on serotonin. Also adisruptive effect of MTX on the metabolisms of glutamate, aspartate, glutamine andGABA emerges (AU)

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Toxic effects of methoxychlor in rat striatum: modifications in several neurotransmitters

Neurotoxic effects of methoxychlor (MTX) are poorly understood at present.This study was undertaken to evaluate the possible effects of MTX in norepinephrine,dopamine and amino acid contents and serotonin turnover in rat striatum. Forthis purpose, adult male Sprague-Dawley rats were administered 25 mg/kg/day ofMTX in sesame oil or vehicle only for 30 days. The neurotransmitters of interestwere measured in the striatum by HPLC. MTX decreased norepinephrine and 5-hydroxyindole acetic acid (5-HIAA) content and serotonin turnover (measured as 5-HIAA/serotonin ratio), and increased glutamate and GABA concentrations. However,the content of serotonin, aspartate, glutamine and taurine was not modified byMTX exposure. These data suggest that MTX exposure inhibits norepinephrine synthesisand serotonin metabolism. The inhibitory effect on norepinephrine could beexplained, at least in part, by the increase of both GABA and glutamate contents.Further studies are needed to understand the effects of MTX on serotonin. Also adisruptive effect of MTX on the metabolisms of glutamate, aspartate, glutamine andGABA emerges (AU)

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Seasonal variations of gonadotropins and prolactin in the laboratory rat. Role of maternal pineal gland.

The laboratory rat, a non-photoperiodic rodent, exhibits seasonal fluctuations of melatonin. Melatonin has been found to be readily transferred from the maternal to the fetal circulation. No data exist on the possible influence of maternal pineal gland upon seasonal variations of the offspring. The aim of the present study was to asses the influence of the maternal melatonin rhythm on the offspring postnatal development of the reproductive hormones LH, FSH and prolactin. Male offspring from control, pinealectomized (PIN-X) and PIN-X + melatonin (PIN-X+MEL) mother Wistar rats were studied at 21, 31, and 60 days of age. Seasonal age-dependent variations were found for all hormones studied in control offspring but PIN-X offspring showed a tendency to have reduced duration or altered seasonal variations. Maternal melatonin treatment to PIN-X mothers partially restored the effect of pinealectomy. The chronological study of LH, FSH, and prolactin in PIN-X offspring also showed an altered pattern as compared to control-offspring. Melatonin treatment to the mothers partially restored the developmental pattern of reproductive hormones. Results of this study indicate that maternal pineal gland of the laboratory rat is involved in the seasonal postnatal development variations of reproductive hormones of the offspring.

Circadian rhythms of prolactin secretion in neonatal female rabbits after acute separation from their mothers.

Newborn rabbits (Oryctolagus cuniculus) are only nursed for 3-5 min every 24 h and show a circadian increase in activity in anticipation of nursing. The objective of this study was to determine, in neonatal female rabbits after acute separation from the doe for 48 h, the changes in 24-h rhythms of plasma prolactin and median eminence and anterior pituitary concentration of dopamine (DA) and serotonin (5HT). In addition, median eminence concentration of the excitatory amino acid transmitters glutamate (GLU) and aspartate (ASP) and of the inhibitory amino acid transmitters gamma-aminobutyric acid (GABA) and taurine (TAU) was measured. A significant 21% increase of circulating prolactin occurred in isolated pups. In controls pups, plasma prolactin levels showed two peaks, during the first half of the light phase and at the beginning of the scotophase, respectively. In the isolated pups, a phase advance of about 4 h occurred for the two prolactin peaks. Hemicircadian changes of median eminence DA were found in controls, whereas a single daily peak (at 17:00 h) was found in the separated pups. Plasma prolactin and median eminence DA correlated significantly and inversely in the control group only. Pituitary DA content exhibited a single peak in controls and a hemicircadian pattern in isolated pups. Plasma prolactin and pituitary DA correlated significantly in isolated pups only 00000. Pup isolation decreased median eminence 5HT levels, augmented pituitary 5HT levels and disrupted their 24 h rhythmicity. Circulating prolactin correlated inversely with median eminence 5HT and directly with adenohypophysial 5HT only in controls. Isolation of pups generally modified the 24 h pattern of median eminence excitatory and inhibitory amino acid content by causing a prominent decrease at the beginning of the light phase. The results indicate that circadian rhythmicity of prolactin secretory mechanisms in female rabbit pups is significantly affected by pup's isolation from the doe.

Oestrus synchronisation of rabbit does at early post-partum by doe-litter separation or ECG injection: Reproductive parameters and endocrine profiles.

Inseminating rabbit does at early post-partum, in combination with early weaning, can increase prolificacy (total kits born and still born per parturition) and decrease parturition intervals. Oestrus synchronisation increases fertility and prolificacy, while decreasing the number of inseminations required for gestation. However, little is known about the effectiveness of different oestrus synchronisation methods at early post-partum. In this study, does (n = 138) were artificially inseminated nine times (over a period of 1 year, kits weaned at 25 days), on day 4 post-partum after separation from the litter (for 48 or 24 h) or 48 h after 25 UI eCG injection. Plasma levels of prolactin and estradiol were also evaluated in a subsample of 12 multiparous lactating does per treatment, on days 2, 3 and 4 post-partum. The three treatments increased overall fertility of multiparous females compared to controls (which were not synchronised), but there were no differences among treatments in total kits born or stillborn. Does treated with eCG had a higher culling rate. The interval between parturitions and the number of inseminations required for gestation tended to decrease with increasing number of inseminations. In lactating does, there was an interaction between treatment and insemination order. Fertility decreased with increasing inseminations in eCG does but tended to increase above control values in the separated does until the fourth insemination. Control lactating does had significantly less kits per parturition compared to treatments, but eCG lactating does had more stillborn kits. Oestradiol levels increased on day 4 post-partum in all synchronised lactating does (and immediately before artificial insemination in 48 h doe-litter separation), so ovarian activity could be stimulated at early post-partum using all treatments. However, the increase could not be explained by prolactin levels, since there were no effects of suckling absence on plasma prolactin in separated does. In conclusion, separating does from the litter before insemination can be just as effective as eCG treatment, especially during for the first four inseminations.

Twenty-four hour rhythm of plasma prolactin in female rabbit pups. Correlation with hypothalamic and adenohypophysial dopamine, serotonin, gamma-aminobutyric acid and taurine content.

Lactation in the rabbit is a nocturnal activity, extremely short and regular, that can be a strong synchronizer for the development of circadian rhythmicity in the pups. In the present study, 24-h rhythmicity of plasma prolactin and median eminence and anterior pituitary content of dopamine (DA), serotonin (5HT), gamma-aminobutyric acid (GABA) and taurine were examined in 11 days old female pups kept under 16 h light:8 h dark photoperiods (lights on at 08:00 h). Groups of six to seven female rabbit pups were killed by decapitation at six different time points throughout a 24-h cycle, starting at 09:00 h. Plasma prolactin levels changed significantly throughout the day, showing two peaks, one at first half of rest span (at 13:00 h) and another one at the beginning of the scotophase (at 01:00 h), just preceding doe visit. Median eminence DA content changed in a bimodal way as a function of time of day, displaying two maxima, at the beginning of the rest span and of the activity phase. Median eminence DA and plasma prolactin correlated significantly in an inverse way. Two maxima in median eminence 5HT levels were found, about 4 h in advance to the prolactin peaks. Circulating prolactin correlated inversely with median eminence 5HT content and directly with adenohypophysial 5HT content. Median eminence GABA content reached its maximum at the beginning of the scotophase and correlated significantly with plasma prolactin concentration. A positive correlation between plasma prolactin and adenohypophysial taurine content was observed. These results show that the circadian rhythmicity in prolactin secretory mechanisms in female rabbit pups develops during the early neonatal life.

Melatonin, immune function and aging.

Aging is associated with a decline in immune function (immunosenescence), a situation known to correlate with increased incidence of cancer, infectious and degenerative diseases. Innate, cellular and humoral immunity all exhibit increased deterioration with age. A decrease in functional competence of individual natural killer (NK) cells is found with advancing age. Macrophages and granulocytes show functional decline in aging as evidenced by their diminished phagocytic activity and impairment of superoxide generation. There is also marked shift in cytokine profile as age advances, e.g., CD3+ and CD4+ cells decline in number whereas CD8+ cells increase in elderly individuals. A decline in organ specific antibodies occurs causing reduced humoral responsiveness. Circulating melatonin decreases with age and in recent years much interest has been focused on its immunomodulatory effect. Melatonin stimulates the production of progenitor cells for granulocytes-macrophages. It also stimulates the production of NK cells and CD4+ cells and inhibits CD8+ cells. The production and release of various cytokines from NK cells and T-helper lymphocytes also are enhanced by melatonin. Melatonin presumably regulates immune function by acting on the immune-opioid network, by affecting G protein-cAMP signal pathway and by regulating intracellular glutathione levels. Melatonin has the potential therapeutic value to enhance immune function in aged individuals and in patients in an immunocompromised state.

Role of melatonin in neurodegenerative diseases.

The pineal product melatonin has remarkable antioxidant properties. It scavenges hydroxyl, carbonate and various organic radicals, peroxynitrite and other reactive nitrogen species. Melatonyl radicals formed by scavenging combine with and, thereby, detoxify superoxide anions in processes terminating the radical reaction chains. Melatonin also enhances the antioxidant potential of the cell by stimulating the synthesis of antioxidant enzymes like superoxide dismutase, glutathione peroxidase and glutathione reductase, and by augmenting glutathione levels. The decline in melatonin production in aged individuals has been suggested as one of the primary contributing factors for the development of age-associated neurodegenerative diseases, e.g., Alzheimer's disease. Melatonin has been shown to be effective in arresting neurodegenerative phenomena seen in experimental models of Alzheimer's disease, Parkinsonism and ischemic stroke. Melatonin preserves mitochondrial homeostasis, reduces free radical generation, e.g., by enhancing mitochondrial glutathione levels, and safeguards proton potential and ATP synthesis by stimulating complex I and IV activities. Therapeutic trials with melatonin have been effective in slowing the progression of Alzheimer's disease but not of Parkinson's disease. Melatonin's efficacy in combating free radical damage in the brain suggests that it may be a valuable therapeutic agent in the treatment of cerebral edema after traumatic brain injury.

Toxic effects of cadmium on GABA and taurine content in different brain areas of adult male rats

This work assesses the possible changes in gamma amino butyric acid (GABA)and taurine content in the hypothalamus, the median eminence and striatum after theexposure to various doses of cadmium. Cadmium chloride (CdCl2) was administeredin the drinking water at the doses of 5, 10, 25, 50 or 100 ppm to adult male rats for 1month. In the anterior hypothalamus, taurine and GABA content decreased with thedose of 10 ppm of CdCl2 only. Cadmium exposure decreased both GABA and taurinecontent in mediobasal hypothalamus except for the 50 ppm dose. In posteriorhypothalamus GABA and taurine content was not affected by cadmium treatment.As far as the median eminence, 5 or 10 ppm of CdCl2 increased taurine concentration,and at a dose of 5 ppm enhanced GABA content. A significant decrease ofGABA and taurine concentration was seen in the striatum at any dose of cadmiumused. The concentration of cadmium increased in the hypothalamus and in the striatumin animals receiving CdCl2 in the drinking water at doses of 25, 50 or 100 ppm.The results indicate that cadmium globally decreased GABA and taurine content inthe brain areas studied through effects that were not dose dependent (AU)

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Toxic effects of cadmium on the regulatory mechanism of dopamine and serotonin on prolactin secretion in adult male rats.

This work was designed to analyze the effects of cadmium on the regulatory mechanism of prolactin in cadmium-exposed rats. Adult male rats were given cadmium at a dose of 25 ppm of cadmium chloride (CdCl2) in the drinking water for 1 month. At the end of the treatment, the rats were killed at six different time intervals throughout a 24 h cycle to measure circulating prolactin levels and dopamine and serotonin content in the median eminence and in both anterior and posterior pituitary. Control and cadmium-exposed animals exhibited significant time of day-dependent variations in plasma prolactin levels and in dopamine and serotonin concentration in all analyzed tissue. Cadmium exposure did not modify the mean values of the hormone around the clock but it modified the amplitude of the secretory peaks at 08:00 and 12:00 h. Cadmium decreased dopamine content in the median eminence, while increased its content in the posterior pituitary and induced a phase advanced peak at 20:00 h. On the other hand, serotonin content was not modified in the median eminence. Only differences in specific time points were observed, while serotonin concentration in anterior and posterior pituitary were increased in cadmium-treated rats. Differences in time peaks were also observed. The negative correlation between plasma prolactin and dopamine content in pituitary, and between plasma levels of the hormone and serotonin content in posterior pituitary, disappeared in cadmium-treated animals.

Toxic effects of cadmium on GABA and taurine content in different brain areas of adult male rats.

This work assesses the possible changes in gamma amino butyric acid (GABA) and taurine content in the hypothalamus, the median eminence and striatum after the exposure to various doses of cadmium. Cadmium chloride (CdCl2) was administered in the drinking water at the doses of 5, 10, 25, 50 or 100 ppm to adult male rats for 1 month. In the anterior hypothalamus, taurine and GABA content decreased with the dose of 10 ppm of CdCl2 only. Cadmium exposure decreased both GABA and taurine content in mediobasal hypothalamus except for the 50 ppm dose. In posterior hypothalamus GABA and taurine content was not affected by cadmium treatment. As far as the median eminence, 5 or 10 ppm of CdCl2 increased taurine concentration, and at a dose of 5 ppm enhanced GABA content. A significant decrease of GABA and taurine concentration was seen in the striatum at any dose of cadmium used. The concentration of cadmium increased in the hypothalamus and in the striatum in animals receiving CdCl2 in the drinking water at doses of 25, 50 or 100 ppm. The results indicate that cadmium globally decreased GABA and taurine content in the brain areas studied through effects that were not dose dependent.

Efecto de la glándula pineal materna en las variaciones hormonales estacionales del eje neuroendocrino-reproductor de los descendientes / Influence of the maternal pineal gland on seasonal variations in the neuroendocrine-reproductive axis in offspring

Fundamento y objetivo: Evaluar la influencia de la glándula pineal materna en las variaciones estacionales de las hormonas luteinizante, foliculostimulante y prolactina, y el peso corporal de la descendencia. Sujetos y método: Se utilizaron ratas hembras Wistar en régimen de luz/oscuridad (12L/12D). Las ratas madres fueron divididas en las 4 estaciones del año en 3 grupos: control, pinealectomizadas (PIN-X) y PIN-X más tratamiento con melatonina (PIN-X + MEL). Se estudiaron los machos descendientes a los 21, 31 y 60 días de edad. Resultados: La PIN-X materna provocó valores aumentados del peso corporal a los 21 y 31 días en invierno y a los 60 días en primavera y en verano. Igualmente, afectó al patrón de desarrollo de hormona luteinizante durante el período juvenil, y de forma estacional en otoño e invierno, mientras que el efecto de PIN-X + MEL influyó en primavera y verano. La PIN-X materna desencadenó un valor significativamente menor de los valores de hormona folículos estimulante a los 60 días, en verano y otoño, pero no afectó al patrón de desarrollo de la prolactina; sin embargo, sí se observó una ligera influencia del tratamiento PIN-X + MEL dependiente de la estación para ambas hormonas. Conclusiones: Nuestros resultados sugieren que durante el desarrollo embrionario el ritmo de melatonina materna puede influir sobre el desarrollo posnatal del eje neuroendocrino-reproductor en una forma dependiente de la estación del año. Estas consideraciones podrían ayudar a comprender cuestiones relacionadas con enfermedades estacionales presentes cada vez con mayor incidencia (AU)

Differential effects of light/dark recombinant human prolactin administration on the submaxillary lymph nodes and spleen activity of adult male mice.

OBJECTIVES: Day/night variations in cellularity, percentage of CD4+, CD8+ and double-positive (CD4+-CD8+) lymphocytes, lipopolysaccharide (LPS)- and concanavalin A (Con A)-induced lymphocyte proliferation and natural killer (NK) activity, and the effect of timed administration of recombinant human prolactin (h-PRL) on the above-mentioned parameters were investigated in the submaxillary lymph nodes and spleen of adult male mice. RESULTS: In controls, the percentage of CD4+, double-positive lymphocytes, LPS- or Con A-induced blastogenic proliferation and NK activity in the spleen differ during the dark phase as compared to the light phase. When administered during the dark period, h-PRL induced immunosuppresion in the percentage of CD4+, double-positive (CD4+-CD8+) lymphocytes. Con A- and LPS-induced lymphocyte proliferation and NK activity as compared to untreated controls. When h-PRL was administered during the light period, the cellularity increased, and h-PRL was immunosuppressive in Con A- and LPS-induced lymphcoyte proliferation and NK activity as compared to controls. Moreover, in control submaxillary lymph nodes the cellularity, percentage of CD8+, double-positive lymphocytes, blastogenic proliferation in the presence of Con A and LPS and NK activity differ when comparing the dark with the light phase. When administered during the dark period h-PRL induced immunosuppression in the percentage of double-positive (CD4+-CD8+) lymphocytes, Con A- and LPS-induced lymphocyte proliferation as compared to controls. When h-PRL is administered during the light period, no effects were observed. CONCLUSIONS: These results indicate the existence of differential day/night variations in the cellular immune response depending upon the lymphoid organ considered. Because of the administration of h-PRL a differential modulation of this circadian variation was also observed.

Superior cervical ganglionectomy differentially modifies median eminence and anterior and mediobasal hypothalamic GABA content in male rats: effects of hyperprolactinemia.

This work was undertaken to analyze the changes in GABA concentrations in the anterior and mediobasal hypothalamus and in the median eminence after acute or chronic superior cervical ganglionectomy (SCGx), and whether high prolactin levels interfere with the effects of SCGx on GABA content. Acute but not chronic SCGx increased GABA content in all the areas studied, as compared to controls. The presence of a pituitary graft abolished the effects of acute SCGx in the median eminence and anterior hypothalamus, as compared to controls, but potentiated its effects in the mediobasal hypothalamus. Chronic SCGx increased GABA content in the mediobasal and anterior hypothalami, as compared to pituitary grafted controls. Acute SCGx decreased plasma prolactin and GH levels, but chronic surgery did not modify these hormone plasma levels. Acute SCGx increased plasma ACTH levels, whereas chronic SCGx did not modify them. Pituitary grafting increased circulating values of prolactin, ACTH and GH, as compared to controls. Acute SCGx did not modify plasma prolactin levels in grafted animals, although it increased plasma GH levels and decreased those of ACTH in this experimental group. Chronic SCGx further increased both plasma prolactin and GH levels, without modifying plasma ACTH levels. These results suggest that SCGx differentially modifies GABA content within the hypothalamus and median eminence. Induction of hyperprolactinemia in the neonatal age interferes with SCGx effects on both GABA content within the hypothalamus and median eminence and the secretory patterns of the pituitary hormones studied.