Showing papers on "Pinealectomy published in 2003"

Melatonin and mammary cancer: a short review.

Abstract: Melatonin is an indolic hormone produced mainly by the pineal gland. The former hypothesis of its possible role in mammary cancer development was based on the evidence that melatonin down-regulates some of the pituitary and gonadal hormones that control mammary gland development and which are also responsible for the growth of hormone-dependent mammary tumors. Furthermore, melatonin could act directly on tumoral cells, as a naturally occurring antiestrogen, thereby influencing their proliferative rate. The first reports revealed a low plasmatic melatonin concentration in women with estrogen receptor (ER)-positive breast tumors. However, later studies on the possible role of melatonin on human breast cancer have been scarce and mostly of an epidemiological type. These studies described a low incidence of breast tumors in blind women as well as an inverse relationship between breast cancer incidence and the degree of visual impairment. Since light inhibits melatonin secretion, the relative increase in the melatonin circulating levels in women with a decreased light input could be interpreted as proof of the protective role of melatonin on mammary carcinogenesis. From in vivo studies on animal models of chemically induced mammary tumorigenesis, the general conclusion is that experimental manipulations activating the pineal gland or the administration of melatonin lengthens the latency and reduces the incidence and growth rate of mammary tumors, while pinealectomy usually has the opposite effects. Melatonin also reduces the incidence of spontaneous mammary tumors in different kinds of transgenic mice (c-neu and N-ras) and mice from strains with a high tumoral incidence. In vitro experiments, carried out with the ER-positive MCF-7 human breast cancer cells, demonstrated that melatonin, at a physiological concentration (1 nM) and in the presence of serum or estradiol: (a) inhibits, in a reversible way, cell proliferation, (b) increases the expression of p53 and p21WAF1 proteins and modulates the length of the cell cycle, and (c) reduces the metastasic capacity of these cells and counteracts the stimulatory effect of estradiol on cell invasiveness; this effect is mediated, at least in part, by a melatonin-induced increase in the expression of the cell surface adhesion proteins E-cadherin and beta(1)-integrin. The direct oncostatic effects of melatonin depends on its interaction with the tumor cell estrogen-responsive pathway. In this sense it has been demonstrated that melatonin down-regulates the expression of ERalpha and inhibits the binding of the estradiol-ER complex to the estrogen response element (ERE) in the DNA. The characteristics of melatonin's oncostatic actions, comprising different aspects of tumor biology as well as the physiological doses at which the effect is accomplished, give special value to these findings and encourage clinical studies on the possible therapeutic value of melatonin on breast cancer.

Effect of pinealectomy on plasma levels of insulin and leptin and on hepatic lipids in type 2 diabetic rats

Abstract: We previously reported that pharmacological melatonin administration to type 2 diabetic rats reduces hyperinsulinemia and improves the altered fatty-acid metabolism. To determine whether melatonin deficiency exacerbates diabetes-associated conditions, we investigated the effect of pinealectomy (i.e. melatonin-deficiency) on plasma hormone levels and lipid metabolism in type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. We compared levels of insulin and leptin, and hepatic lipids in pinealectomized OLETF (PO) rats, sham-operated OLETF (SO) rats and sham-operated healthy Long-Evans Tokushima Otsuka (LETO) (SL) rats 16 and 30 wk after the operation. Plasma glucose and triglycerides were increased in SO and PO rats 30 wk after operation compared with age-matched SL rats. Pinealectomy caused an increase in free cholesterol among the plasma lipids, as compared with SO rats. Sixteen weeks after pinealectomy, typical hyperinsulinemia was observed in PO rats (3.47-fold increase, P < 0.01) as compared with SL rats, whereas at 30 wk, the plasma levels of insulin in PO and SO rats had decreased and there was no significant difference among the three groups. Hepatic triglycerides were increased (1.54-fold, P < 0.005) in PO rats, compared with SO rats. Hepatic acyl-CoA synthetase (ACS) activity was significantly augmented in PO rats at 30 wk (10%, P < 0.01 versus SO group), while microsomal triglyceride transfer protein (MTP) decreased (-27% versus SO, P < 0.05); thus, the increased ACS activity and decreased MTP might have a role in the accumulation of hepatic triglycerides in PO rats. In summary, pinealectomy causes severe hyperinsulinemia and accumulation of triglycerides in the liver, probably owing to the loss of the nocturnal melatonin surge.

Calorie restriction reduces pinealectomy-induced insulin resistance by improving GLUT4 gene expression and its translocation to the plasma membrane.

Abstract: The present study aimed to investigate insulin sensitivity and GLUT4 expression protein in pinealectomized rats, as well as to determining the effects of melatonin and calorie restriction on the changes induced by pinealectomy. Wistar rats were pinealectomized (Pinx) or sham operated (Sham), and studied 30 days later. Melatonin replacement treatment (50 g/100 g body weight) was continued for 30 days after pinealectomy. Calorie restriction was performed by offering 60% of the standard food intake. In vivo insulin sensitivity was evaluated using the glucose disappearance constant (kITT) during an insulin tolerance test, and GLUT4 mRNA and protein were assessed by Northern and Western blotting, respectively. The in vitro effect of melatonin on GLUT4 protein content in plasma membrane was investigated in adipocytes isolated from intact rats. Compared with Sham rats, Pinx rats showed decreased kITT (40%), GLUT4 expression in white adipose tissue (WAT, approximately 70%), and unchanged GLUT4 expression in skeletal muscle. Melatonin treatment in Pinx rats restored the kITT and GLUT4 protein to control values. No in vitro effects of melatonin (10-9 m) upon GLUT4 protein were observed. Calorie restriction of Pinx rats increased their kITT value ( approximately 40%), total GLUT4 protein content ( approximately 240%) and its translocation to the plasma membrane ( approximately 80%) in WAT. The results show that pinealectomy, for lack of melatonin, decreased insulin sensitivity as well as GLUT4 gene expression. Calorie restriction improved insulin sensitivity in Pinx rats, and this was related to increased GLUT4 gene expression and insulin-induced GLUT4 translocation to the plasma membrane in WAT.

The relationship between bone metabolism, melatonin and other hormones in sham-operated and pinealectomized rats.

Abstract: Objective The influence of pinealectomy and long-term melatonin (MEL) administration on circadian oscillations of selected biochemical markers of bone metabolism [serum alkaline phosphatase (ALP) activity, carboxyterminal propeptide type I procollagen (PICP) and carboxyterminal telopeptide type I collagen (ICTP) concentrations as well as urinary excretion of hydroxyproline (HYP) and Ca] and possible involvement of circadian secretion of IGF-I, parathyroid, thyroid, adrenal cortex and gonads function in this mechanism was evaluated. Methods Studies were performed in 192 adult male Wistar rats weighing 145 +/- 9 g which were subjected to pinealectomy or sham operation. In half of the animals from each group MEL (Sigma, USA) in a dose of 50 mg/100 g b.w. was administered intraperitonealy (daily between 17.00 and 18.00 h for a 4-week period). Material for studies (blood and urine) was collected every 3 hours during a day. Hormones, PICP and ICTP concentrations were determined with the use of RIA methods. whereas ALP, HYP and Ca values - spectrophotormetrically. Results The study has shown that pinealectomy had an inducing, while exogenous MEL a suppressing effect upon the level of investigated biochemical markers of bone metabolism. Furthermore, substantial changes in the values of amplitude and phase of their circadian oscillations were shown. Distinct, dependent on the time of day disturbances in circadian fluctuations of PICP, ICTP, HYP and Ca showing generally negative correlation with changes in endogenous MEL concentrations and positive with IGF-I and corticosterone (B) levels were found. In addition, changes in circadian oscillations of ALP and PICP correlated negatively with daily oscillations of calciotropic hormones and B. However, ICTP, HYP and Ca concentrations correlated positively with circadian fluctuations of B and FT3 (the latter only in sham operated rats receiving MEL). Conclusions This study showed that both pinealectomy and long-term MEL administration influence the circadian rhythm of bone metabolism and that an important role in the mechanism of this dependence is played by the changes of endogenous MEL levels. Secondary changes in circadian oscillations of calciotropic hormones, IGF-I and corticosterone concentrations, caused by pinealectomy and long-term MEL administration result in altered bone metabolism rhythm.

The role of pineal gland in breast cancer development.

Abstract: The role of the modulation of the pineal gland function in development of breast cancer is discussed in this review. An inhibition of the pineal function with pinealectomy or with the exposure to the constant light regimen stimulates mammary carcinogenesis, whereas the light deprivation inhibits the carcinogenesis. Epidemiological observations on increased risk of breast cancer in night shift workers, flight attendants, radio and telegraph operators and on decreased risk in blind women are in accordance with the results of experiments in rodents. Treatment with pineal indole hormone melatonin inhibits mammary carcinogenesis in pinealectomized rats, in animals kept at the standard light/dark regimen (LD) or at the constant illumination (LL) regimen. Pineal peptide preparation Epithalamin and synthetic tetrapeptide Epitalon (Ala-Glu-Asp-Gly) are potent inhibitors of mammary carcinogenesis in rodents and might be useful in the prevention of breast cancer in women at risk.

Pineal gland (melatonin) affects the parturition time, but not luteal function and fetal growth, in pregnant rats.

Abstract: The purpose of the present study was to investigate the role of pineal gland (melatonin) on parturition time, luteal function, and fetal growth in pregnant rats. Cycling rats were subjected to pinealectomy or sham operation under ether anesthesia; and pinealectomized rats immediately underwent implantation of a melatonin capsule (PINX + Mel group) or a vehicle-containing capsule (PINX group), and sham operated rats also underwent implantation of a vehicle-containing capsule (control group). All rats were maintained under the same photoperiod conditions (14 L:10 D) and were induced pregnancy. Blood samples were obtained on days 7, 12, 15, 17, 19, and 21 of pregnancy to measure serum progesterone concentrations, and parturition times were recorded on days 22 and 23. In the next experiment, pregnant PINX rats received subcutaneous injection of melatonin (10 microg/body) at 08:00 h (PINX + 8 h group) or at 20:00 h (PINX + 20 h group) from day 15 to the end of pregnancy, and parturition times were recorded. Parturition times of rats in the PINX group, the PINX + Mel group or the PINX + 8 h group, but not the PINX + 20 h group, were significantly different compared with those in the control group. Pinealectomy or melatonin implantation did not affect serum progesterone concentrations during pregnancy or the number and weight of fetuses or corpora lutea. The present results indicate that pineal gland (melatonin rhythm) synchronizing with photoperiodic rhythm is likely to be an important determinant of parturition time, but it does not affect progesterone production or fetal growth in pregnant rats.

Pinealectomy changes rat ovarian interstitial cell morphology and decreases progesterone receptor expression.

Abstract: The aim of this study was to evaluate the rat ovarian morphological and function changes after pinealectomy (px). Two months after px, young female Wistar rats were sacrificed and the right ovaries were analysed morphologically and the left ovaries were used for steroid receptor binding experiments. Blood was collected and steroid hormone and melatonin levels were measured using radioimmunoassay kits. Results revealed that in the px group the rat ovaries had an increase in the number of atretic follicles and interstitial cells. These cells showed hyperactivity features on transmission electron microscopy and morphometric analysis (p < 0.05 compared with control and sham groups). Px-group serum showed an increase in estradiol (p < 0.05) and a decrease in progesterone levels (p < 0.05) compared with other groups. Moreover, progesterone receptor expression was lower than control and sham groups (p < 0.05). We postulate that pinealectomy leads to many morphological alterations of rat ovaries that are associated with functional changes in steroidogenesis and a decrease in progesterone receptor expression.

Pinealectomy and zinc deficiency have opposite effects on thyroid hormones in rats.

Abstract: The present study was conducted to investigate how pinealectomy and zinc deficiency separately or in combination affected thyroid hormones in rats. The study was carried out on 40 Sprague–Dawley male rats. The rats were equally allocated to four groups: Group 1 (control group), Group 2 (zinc‐deficient group), Group 3 (pinealectomized group) and Group 4 (pinealectomized and zinc‐deficient group). At the end of a 4‐week study period, the rats were decapitated and blood samples were taken. The samples were examined in terms of plasma zinc, melatonin, free and total T3, T4, and TSH. It was found that free T3 and T4 levels in the pinealectomized group (Group 3) were higher than all others ( p < 0.01) while free T3, T4, and TSH levels in the zinc‐deficient group (Group 2) were lower than all others ( p < 0.01). Free T3 and T4 levels in the pinealectomized zinc‐deficient group (Group 4) were lower than those in Groups 1 and 3 and higher than those in Group 2 ( p < 0.01). The findings obtained at the end of the s...

Effect of melatonin suppression on scoliosis development in chickens by either constant light or surgical pinealectomy.

Abstract: STUDY DESIGN This study was designed to compare the effect of suppression of melatonin secretion by bright light in chickens with that of surgical pinealectomy OBJECTIVE To determine whether suppression of melatonin secretion without surgery in chickens can result in scoliosis development SUMMARY OF BACKGROUND DATA Pinealectomy in chickens consistently produces scoliosis with anatomic characteristics similar to those of human idiopathic scoliosis Conversely, cutting of the pineal stalk without removal of the pineal gland will also result in scoliosis This study addresses the question of whether constant bright light can induce scoliosis formation, because it is well known that 24-hour bright lighting conditions can suppress the secretion of melatonin to an equivalent level as pinealectomy MATERIALS AND METHOD Seventy-seven newborn Nihon chickens were separated into three groups A control group (n = 21) with no surgery performed; a pinealectomy group (n = 15) that served as surgical controls; and a constant light group (n = 41) The first two groups were kept together in a strict 12-hour light-dark cycle, whereas the third group was separately kept with constant lighting conditions (>100 lux) All the chickens were radiographed at two weekly intervals, and blood was taken during the middle of the light and dark cycles for serum melatonin assay using ELISA RESULTS Fifty-four percent of the pinealectomized chickens had scoliosis develop by 6 weeks None of the constant-light chickens or controls had scoliosis develop for up to 11 weeks Measurements of serum melatonin levels of the constant light group confirm that secretion is suppressed CONCLUSION This study suggests that for scoliosis to develop in chickens, the surgical operation itself is important and challenges the role of melatonin as an isolated etiological factor in the development of scoliosis

The effects of pineal gland transplantation on the production of spinal deformity and serum melatonin level following pinealectomy in the chicken

Abstract: Pinealectomy frequently produces spinal deformity in some animal models, but the precise biological mechanism of this phenomenon remains obscure. The current study investigated the effects of an autograft pineal body on the development of spinal deformity and serum melatonin (MLT) concentration after pinealectomy in the chicken. Thirty-six chickens (2 days of age) were divided into three equal groups. While the removal of the pineal gland was performed in groups B and C, a pineal body autograft was surgically implanted into the body wall musculature only in the pineal transplantation group (group C). Chickens in which no surgical intervention was performed served as intact controls (group A). Posteroanterior radiographs of the spines of the chickens were taken at the age of 8 weeks. These were used to determine Cobb angles and to measure the rib-vertebra angles (RVA) on the concave and convex sides of the curves, from which data the difference between the convex and concave RVA (the RVAD) was calculated. At the end of the study, serum MLT levels were determined using the enzyme-linked immunosorbent assay method, and histopathological examination of specimens from all the groups was performed. The results were compared using one-way analysis of variance followed by Duncan's test for pairwise comparisons or by the Kruskal-Wallis test followed by the Mann-Whitney U tests for comparisons between two groups. In this study, the serum MLT levels in groups B and C were significantly lower than those in group A (P<0.05). However, scoliosis developed in only 7 of 12 (58%) in group B and 6 of 12 (50%) in group C. The average Cobb angle and RVAD in groups B and C were significantly larger than those found in group A (P=0.000 and P=0.001, respectively). Interestingly, there were no significant differences in either serum MLT levels or development of scoliosis between groups B and C. From the results of the current study, it is evident that the intramuscular pineal gland transplantation following pinealectomy in young Hybro Broiler chickens has no significant effect on the development of spinal deformity and serum MLT level. In the light of this result, the role of MLT in the development of spinal deformity in chickens after pinealectomy remains controversial, and further investigations are warranted.

Primary thoracolumbar scoliosis in pinealectomized chickens.

Abstract: STUDY DESIGN This study examines the gross anatomic changes in the chicken spine after pinealectomy and was undertaken because initial observation suggested that the pattern of curve development appears to be different from that reported in the literature. OBJECTIVE To characterize the spinal deformity in chickens after pinealectomy. SUMMARY OF BACKGROUND DATA The most common curve pattern seen after pinealectomy in chickens is said to be thoracic curves with structural changes and rotation. This is based largely on radiographic observations and forms the basis of the claim that chicken and human adolescent idiopathic scoliosis are similar. METHOD Thirty-five chickens were divided into 2 groups, a pinealectomy group (n = 25) and a control group with no surgery performed (n = 10). The spines were harvested at 3 months of age and examined visually, by radiographs and computed tomography scans. RESULTS Thirteen out of 25 (52%) of the pinealectomized chickens developed scoliosis. In contrast to previous studies, all the curves were located at the thoracolumbar junction with the apex at either T7 or L1. Structural changes including apical vertebral wedging, lordosis (mean of 14.3 degrees ), and rotation (mean of 14 degrees ) were seen in all cases. Pelvic wing deformity was seen in all cases and significantly contributed to the posterior rotational hump. CONCLUSION The primary curve in these chickens is at the thoracolumbar junction. Previous reports of curve pattern based on radiographic findings would not have identified these as the thoracolumbar junction is obscured by the bony pelvis and heavy musculature. The finding of pelvic wing deformity has not been previously reported, and raises the question as to whether these curves are secondary to asymmetric muscle pull.

Toward a seasonal model of the circadian system: the case of Ruin lizards.

Abstract: The pineal gland plays a role in the seasonal re-organization of the circadian system that occurs in Ruin lizard Podarcis sicula. In fact, either pinealectomy or melatonin implants induce an immediate transition from the circadian locomotor pattern typical of summer to the circadian locomotor pattern typical of spring or autumn. Furthermore, the degree of involvement of melatonin and the pineal in circadian organization changes dramatically with season: 1. The effects of pinealectomy, as well as those of melatonin implants on circadian locomotor rhythms are strong in summer and weak in the other seasons; 2. Daily melatonin injections entrain locomotor rhythms in summer, but not in other seasons; 3. A phase response curve for melatonin was generated in summer, but not in winter; 4. Daily injections of luzindole, an antagonist for melatonin receptors alter locomotor rhythms in summer, but not in other seasons; 5. A robust pineal-dependent circadian rhythm of circulating melatonin exists in summer, but not in spring or in autumn. This confirms that the central role of the pineal in determining circadian organization in summer and the marginal role of the pineal in either spring or autumn are respectively due to appearance (summer) or disappearance (spring, autumn) of a circadian melatonin signal in the circulation.

Effect of pinealectomy on circadian rhythm of spermatogenesis.

Abstract: The mitotic index of spermatogonia and 24-h dynamics of stages IV, VI, and XIV of spermatogenic cycle are characterized by circadian rhythm. No circadian rhythm was detected for 11 of 14 stages. Pinealectomy led to an increase of the mitotic index of spermatogonia but did not modulate the incidence of spermatogenic cycle stages, and led to disappearance of the circadian rhythm of both the mitotic index and spermatogenic cycle stages.

Annual variation of plasma melatonin following pinealectomy and melatonin administration in Indian tropical rodent, Funambulus pennanti

Abstract: Pinealectomy (Px) and melatonin (Mel) administration is known for its effect on reproductive and behavioural rhythms. To date no report is available to suggest the effect of Px and Mel administration on the annual variations of plasma Mel itself in any tropical seasonally breeding rodent. We report here that a statistically significant annual oscillation of Mel existed in sham operated control squirrel, F. pennanti. The exact peak value of Mel was noted some time in November (~13th ± 8 days), which was certainly due to short photoperiod and low ambient temperature. Px decreased the melatonin level most significantly. Mel injection to Px squirrel entrained the phase of Mel, though the amplitude was not completely achieved but had a peak melatonin concentration in January (~2 months phase delay). Exogenous Mel administration to sham operated squirrel decreased amplitude of melatonin during the months of March-July leading to early gonadal regression but could not alter the amplitude of Mel in November and December, while the peak value was phase delayed by ~2 months (January). We may suggest, therefore, that the pineal gland of this squirrel is essential for maintaining its own rhythm, which is an adaptive significance of this tropical rodent for the perpetuation of the species.

Effect of pinealectomy on mastocyte count in the thymus of rats

Abstract: There some evidences that endocrine glands have marked influences on mast cells count The study was conducted to determine whether or not difference in mast cell count occurs in thymus gland of pincalectomized rats and to examine also sex difference in mast cell count under these condition adult Wistar rats were used. Pinealectomy was performed under light ether anesthesia. All animals were sacrificed by decapitation at 4 weeks after treatment. Samples were stained in Alcian-blue-PAS and, using Weibls multipurpose test system, the volume density (Vv), numerical density (Nv) and average volume of mastocytes were calculated. Analysis of morphometry has confirmed statistically significant increase in numerical density of mastocytes of pinealectomized female rats. The average volume of mastocytes has been also increased in both sex of animals after pinealectomy. The data from present studies show that there is marked sexual difference in reaction of mast cells after pinealectomy.

Effects of pinealectomy on insulin resistance in Otsuka long-evans Tokushima fatty rats: Physiological role of melatonin in the pathogenesis of type 2 diabetes

Abstract: We examined the role of melatonin in the pathogenesis of diabetes in the Otsuka Long-Evans Tokushima Fatty (OLETF) rat, which served as a model of type 2 diabetes. Six-week-old male OLETF rats were pinealectomized (PINX) and were then subjected to an oral glucose tolerance test (OGTT) and glucose clamping at 33 weeks old. Their liver and quadriceps muscle glycogen levels as well as their plasma levels of various hormones were measured at 35 weeks old. Sham-operated OLETF rats (SO group) displayed weight gain and visceral fat accumulation, exhibited hyperglycemia and hyperinsulinemia during OGTT, and demonstrated a decreased glucose infusion rate (G1R) on glucose clamping. The controls for the above tests were sham-operated Long-Evans Tokushima Otsuka rats (SL group). The PINX OLETF rats (PO group) exhibited similar hyperglycemia and hyperinsulinemia during OGTT to that seen in the SO group, but showed a significant decrease in either GIR on glucose clamping or glycogen content in their quadriceps muscles in comparison to the SO group. However, there were no differences in daytime plasma melatonin, other hormones, or other factors between the SO and PO rats. Our findings indicate that PINX in OLETF rats significantly increases insulin resistance and decreases the glycogen content in peripheral muscles, supporting a role for the pineal gland in the pathogenesis of type 2 diabetes, probably through circadian fluctuations in plasma melatonin release.

International Congress on Hormonal Steroids and Hormones and Cancer Melatonin and mammary cancer: a short review

Abstract: Melatonin is an indolic hormone produced mainly by the pineal gland. The former hypothesis of its possible role in mammary cancer development was based on the evidence that melatonin down-regulates some of the pituitary and gonadal hormones that control mammary gland development and which are also responsible for the growth of hormone-dependent mammary tumors. Furthermore, melatonin could act directly on tumoral cells, as a naturally occurring antiestrogen, thereby influencing their proliferative rate. The first reports revealed a low plasmatic melatonin concentration in women with estrogen receptor (ER)-positive breast tumors. However, later studies on the possible role of melatonin on human breast cancer have been scarce and mostly of an epidemiological type. These studies described a low incidence of breast tumors in blind women as well as an inverse relationship between breast cancer incidence and the degree of visual impairment. Since light inhibits melatonin secretion, the relative increase in the melatonin circulating levels in women with a decreased light input could be interpreted as proof of the protective role of melatonin on mammary carcinogenesis. From in vivo studies on animal models of chemically induced mammary tumorigenesis, the general conclusion is that experimental manipulations activating the pineal gland or the administration of melatonin lengthens the latency and reduces the incidence and growth rate of mammary tumors, while pinealectomy usually has the opposite effects. Melatonin also reduces the incidence of spontaneous mammary tumors in different kinds of transgenic mice (c-neu and N-ras) and mice from strains with a high tumoral incidence. In vitro experiments, carried out with the ER-positive MCF-7 human breast cancer cells, demonstrated that melatonin, at a physiological concentration (1 nM) and in the presence of serum or estradiol: (a) inhibits, in a reversible way, cell proliferation, (b) increases the expression of p53 and p21WAF1 proteins and modulates the length of the cell cycle, and (c) reduces the metastasic capacity of these cells and counteracts the stimulatory effect of estradiol on cell invasiveness; this effect is mediated, at least in part, by a melatonin-induced increase in the expression of the cell surface adhesion proteins E-cadherin and β1-integrin. The direct oncostatic effects of melatonin depends on its interaction with the tumor cell estrogen-responsive pathway. In this sense it has been demonstrated that melatonin down-regulates the expression of ERα and inhibits the binding of the estradiol–ER complex to the estrogen response element (ERE) in the DNA. The characteristics of melatonin’s oncostatic actions, comprising different aspects of tumor biology as well as the physiological doses at which the effect is accomplished, give special value to these findings and encourage clinical studies on the possible therapeutic value of melatonin on breast cancer.

Augmentation of age·related changes of somatotrophs of life-long melatonin deficient rats

Abstract: Many studies indicate connection between pineal gland function ami growth hormone (GH)-insulin-like growth factor (lOF-I) axis in mammals, but their results are not always synonymous (Nir, 1978; Mess, 1983), Pinealcctomy abolishes a decrease of GH concentration in the pituitary gland-of rats, as well as in plasma caused by constant darkness (Relkin, 1972). Ronnekleiv and Me Cann (1978) detected the decrease of GH secretion in rats after pinealcctomy during the day and a lack of the effect at night. Other investigators indicated intensification of circadian fluctuations of GR after pincalcctomy in rats with small increase of daily secretion (Niles et aI., 1979).Progressive and irreversible physiological decline is a characteristic of all organisms late in life, Many studies indicating functional alterations in pars distalis cells accmpanied with aging (Mitchell et at, 1995; Velasco et aI., 1998; Velduis,2000). Pinealcctomy is known to result in a clear decrease in the concentration of circulating melatonin (Gauer et al., 1992). Growth hormone rhythm was suppressed in the pinealectomized rats (Ostrowska et al., 2001). The dysfunctional processes that are a result of macromolecular damage constitute what is referred to as the free radical theory of aging (Sohal and Weindruch, 1996), Numerous reports documented protective actions of melatonin in various modelsof oxidative stress (El-Sokkary et al., 1999; Lee et al., 2002). This is due to its high efficacy as a free radical scavenger and indirect antioxidant (Tan et al., 2002). Additionally, melatonin stimulates the activities of enzymes that metabolize reactive species (Reiter et aI., 2000) and maintains cell membrane fluidity at an optimal level (Garcia et al., 1998). Melatonin was found to decrease with aging (Lee et aI., 2002). Reiter et al. (1999) reported that aging in the pineal-intact animals was associated with increased levels of lipid peroxidation (in the lung, kidney and skin). togethcrwith rises in an oxidatively damaged DNA (in liver, kidney and pancreas), and in the levels of protein carbonyls (in the liver). Likewise, advanced age was associated with a significant decrease in membrane fluidity of hepatic rnicrosomcs inpineal-intact rats. For all of these parameters and in a number of organs, pinealectomy caused further increase in the indices of oxidative damage. The aim of this work was to investigate the ultrastructural alterations in somatotrophcells that result from melatonin deficiency in aged (Pineal-intact) rats and to test whether further induced reduction of melatonin by pinealectomy augment these alterations, trying to detect the role of mclaronin in the aging process.

C cells in the thyroid of pinealectomized rats

Abstract: PURPOSE: To study quantitatively C cells in the thyroids of non-isogenic rats to determine the possible effects of pinealectomy on the number of these cells, and consequently on the synthesis and secretion of calcitonin. METHODS: Twenty male rats of an outbred strain (200-300 g) were used in the present study. One group of 10 animals was pinealectomized 50 days prior to sacrifice. Thyroid tissue was stained for calcitonin (Dako Corporation) at a 1:1500 dilution. The number of C cells observed was expressed as number of cells/cm2. Data were analyzed statistically by Mann-Whitney test. RESULTS: The number of C cells in pinealectomized and normal animals ranged from 489 to 2084 per cm2 and 227 to 1584 per cm2, respectively, a difference that was statistically significant (P <0.05). CONCLUSIONS: These results showed consistent differences in the number of C cells after pinealectomy when compared to controls. We believe that pinealectomy increases the number of C cells in the rat thyroid.