Regulation of leptin gene expression and secretion by steroid hormones.

Previous work has shown that 17 beta-estradiol is the primary ovarian signal regulating body weight and adiposity, although its mechanisms of action remain unclear. We hypothesized that 17 beta-estradiol could enhance leptin levels as a mechanism of its anorectic effects. Administration of 5 microg 17 beta-estradiol subcutaneously (s.c.) for 2 days significantly elevated leptin mRNA levels in adipose tissue as compared to vehicle controls (P < 0.003). A time-course administration of estrogen showed increased mRNA levels in adipose tissue between 6 and 12 h after estrogen injection as compared to vehicle controls (P < 0.03). Corresponding to the increased leptin mRNA levels at 6 and 12 h, elevated plasma leptin levels were observed at 12 h after estrogen administration as compared to controls (P < 0.05). Administration of progesterone (1 mg/rat) after estradiol injection did not enhance the elevated leptin mRNA levels in adipose tissue. Serum leptin levels from cycling rats did not differ significantly between metestrous and proestrous animals. In conclusion, the present studies demonstrate that 17 beta-estradiol can regulate leptin gene expression and secretion in the female rat, thus providing a better understanding of the possible anorectic effect of estrogens.     

Regulation of leptin by steroid hormones in rat adipose tissue.

We investigated if steroid hormones regulate the secretion and the expression of leptin in female and male rat adipose tissue fragments in vitro. Dexamethasone time and dose-dependently increased the secretion and mRNA expression of leptin with a half-maximal stimulation of approximately 1 nM. A time-course revealed a maximal stimulatory effect of 17 beta-estradiol after 24 hours. In male adipose tissue 17 beta-estradiol increased leptin secretion (32% by 50 nM 17 beta-estradiol, P = 0.07 and 34% by 500 nM 17 beta-estradiol, P < 1780.05) after 24 hours. An additional effect of estrogen was seen in the dexamethasone (50 nM) stimulated cells (38% with 50 nM 17 beta-estradiol, P < 0.05 and 48% by 500 nM 17 beta-estradiol, P < 0.05). Basal secretion of leptin was equal in female and male adipose tissue, whereas the effects of 17 beta-estradiol (50 nM) and dexamethasone were significantly increased in female as compared with male adipose tissue. Progesterone, testosterone, dihydrotestosterone and dehydroepiandrostendione-sulfate neither affected leptin secretion in male nor female adipose tissue in vitro. Furthermore, to investigate the effect of estrogen female rats were ovariectomized (OVX) and the adipose tissue was incubated in vitro and compared with adipose tissue leptin secretion from sham operated rats (SHAM), and with ovariectomized rats treated with 17 beta-estradiol (EST). A decreased basal and dexamethasone-stimulated leptin secretion from OVX rats compared with SHAM rats was found (P < 0.005) whereas 17 beta-estradiol treatment of ovariectomized rats maintained a normal leptin secretion. However, the dexamethasone stimulation was equally increased above basal levels in SHAM, OVX and EST rats (3.7 +/- 1.2, 2.9 +/- 0.8, 4.2 +/- 1.4, NS, ANOVA) respectively.     

Size-specific spawing pattern in ayu,Plecoglossus altivelis

The spawning pattern and relationship to body size at maturation of amphidromous and land-locked forms of ayu,Plecoglossus altivelis, was investigated. Ovarian eggs of prespawning females showed a multimodal size distribution, regardles of body size, indicating that all the females were potentially a batch spawners. The spawning schedules of individual fish were described under simulated spawning conditions. Most large-sized females died soon after their first spawning, whereas approximately half of the medium and small-sized females successfully completed a second spawning some two weeks after the first. Such a size-specific spawning pattern was common to both forms, but development of a third batch of ovarian eggs after the second spawning occurred only in the land-locked form. Spawning tactics in ayu were related to offspring survival and adult mortality during spawning season.     

Elevated levels of oxidative DNA damage activate p53 and caspases in brain of ayu with aging

It is well known that ayu (Plecoglossus altivelis) die after spawning. Their lifespan is known to be only 1 year; possibly one contributing factor to post‐spawning mortality in ayu is the enhanced oxidative stress, probably inducing DNA damage and subsequent DNA repair systems (i.e. phosphorylated p53), which in turn may cause apoptosis and a shortened lifespan. To examine this possibility, we surveyed p53 and its phosphorylation state, oxidative DNA damage by measuring the levels of 8‐hydroxy‐2′‐deoxyguanosine, and the induction of apoptosis by measuring levels of caspase‐3, ‐9/6 in the brain at different stages. Accumulation of oxidative stress in brain DNA was accompanied by caspase‐3, ‐9/6, and stimulates p53 through the phosphorylation of this p53 (specifically residue Ser 15) in ayu brain with aging.     

Serum leptin in short children born small for gestational age: dose-dependent effect of growth hormone treatment

OBJECTIVE: To study the effects of different regimens of growth hormone (GH) treatment on serum leptin levels in 78 short prepubertal children born small for gestational age (SGA). METHODS: The children were originally included in two independent multicenter trials, one in Belgium and one in the Nordic countries. SGA children were randomized either to remain untreated or to be treated with GH at a daily dose of 0.1, 0.2 or 0.3 IU/kg for 2 years. Thereafter, treatment was continued for another 2 years in the Nordic children, whereas it was discontinued in the Belgian children. RESULTS: In the GH treatment groups, a significant dose-dependent decrease in leptin levels was found during the first year of therapy, with a mean decrease of 13, 23 and 32% in the groups receiving GH at 0.1, 0.2 and 0.3 IU/kg, respectively. When high-dose treatment was interrupted, serum leptin increased within 1 year to pretreatment levels. CONCLUSION: Serum leptin levels in short children born SGA are transiently reduced by GH treatment in a dose-dependent fashion. The most pronounced changes in serum leptin were documented within the first year after initiation and withdrawal of high-dose GH treatment.     

Growth hormone treatment downregulates serum leptin levels in children independent of changes in body mass index

The changes in serum leptin levels during growth hormone (GH) treatment were studied in 27 children, 17 with GH deficiency (GHD), 10 with idiopathic short stature (ISS), and 9 with Prader-Willi syndrome (PWS). Within 1 month of GH treatment, serum leptin levels decreased by 40% in the GHD children (p < 0.01). There was no significant change in serum leptin level in the children with ISS. In children with PWS, the mean serum leptin level decreased by almost 60% after 3 months of treatment (p < 0.001). Thereafter, no further decline was observed in any of the 3 groups. Changes in body composition became evident first after the 3 months of treatment. In the GHD children, the BMI was unchanged while the mean body fat percentage was 2.7% lower after 1 year of GH treatment (p < 0.05). In the ISS children, neither BMI nor body fat percentage were significantly changed during treatment. The PWS children exhibited a significant decrease in BMI after 6 months of GH treatment without any further change during the remaining period of treatment. In this group, the mean body fat percentage decreased from 42 +/- 2.4 to 28 +/- 2.2% after treatment (p < 0.001). The finding that the fall in leptin occurs before changes in body composition become detectable suggests a direct effect of GH on leptin production, metabolism, or clearance.     

Leptin,ghrelin, and energy metabolism of the spawning burbot (Lota lota,L.)

The aim of this study was to investigate the energy metabolism of the burbot (Lota lota, n=38) before, during, and after spawning, which represents the greatest annual metabolic demand for the species. A decrease in body mass, relative weight of the livers, and glycogen concentration of the livers was observed toward the end of spawning. The prespawning period was characterized by high rates of liver glycogenolysis and lipid mobilization. Also, plasma triiodothyronine and sex steroid levels were high before reproduction. During spawning, liver lipolysis was reduced and muscle glycogenolysis stimulated. The levels of triiodothyronine and sex steroids decreased. After reproduction, liver glycogenolysis was suppressed and the rate of gluconeogenesis increased. Thyroid hormone levels were elevated after spawning. Leptin protein and a ghrelin-immunoreactive peptide were detected in burbot plasma. Their concentrations were relatively low before and during reproduction but increased after spawning. The functions of leptin and the ghrelin-immunoreactive peptide in the physiology of the burbot are not consistent with the models of their function in mammals.     

Female Mate Preference and Male Mating Success of Ayu Fish,Plecoglossus altivelis (Osmeridae) under a Promiscuous Mating System

The ayu, Plecoglossus altivelis, is known to show wide variation in adult body size. We examined the spawning behavior in experimental spawning groups of fish in which male body size varied. Males never competed with each other for females or spawning site, while females spawned repeatedly, 17–97 times depending on body size, with previous or novel males. Males exhausted their sperm after a single mating episode, on average, regardless of body size. Moreover, repeated sperm production apparently reduced the residual lifespan. Females preferred mating simultaneously with more than one male and allowed males of body size similar to their own to mate more frequently. Thus the largest male within a spawning group was not always the most successful at mating, but mating success of any given male appears to depend upon body size distribution of females within the population. Female mate preference has apparently evolved to ensure complete fertilization under circumstances where males have been selected to economize sperm output during any one mating episode.     

Interferon-alpha suppresses leptin levels: studies in interferon-alpha treated patients with hepatitis C virus infection and murine adipocytes

Leptin is an adipocyte-derived protein, which signals the status of current energy stores and energy intake to the central nervous system. Interferon-alpha therapy is frequently associated with loss of appetite and weight reduction. In this study, we tested whether interferon-alpha is able to regulate leptin synthesis. We therefore determined leptin plasma concentrations in thirteen patients with chronic hepatitis C who were treated with 1 x 10(7) IU interferon-alpha daily, up to 21 days after initial treatment. Furthermore, leptin concentrations and messenger RNA levels were quantified in interferon-alpha-treated and untreated murine adipocytes. After reaching peak plasma levels at 12 hours, probably reflecting the circadian rhythm, leptin concentrations fell and were significantly lower after 14 days. They remained significantly decreased 17 and 21 days after the start of the interferon-alpha treatment. In murine adipocytes exposed to interferon-alpha, leptin secretion was significantly decreased while messenger RNA levels remained unchanged. Our data suggest that, in contrast to proinflammatory cytokines such as interleukin-1, interferon-alpha suppresses leptin secretion in adipose tissue. We therefore hypothesize that loss of weight and appetite in interferon-alpha-treated patients with chronic hepatitis C might not be due to an elevation of leptin resulting in signals of increased energy stores in the brain.     

Changes in body mass,serum leptin,and mRNA levels of leptin receptor isoforms during the premigratory period in <Emphasis Type="Italic">Myotis lucifugus</Emphasis>

Migration and hibernation in mammals may be preceded by a period of leptin resistance, which may in part account for the increasing adiposity and body mass that occurs during these periods. We hypothesized that hypothalamic expression of leptin receptor mRNA would decrease during the premigration (PM) period in the little brown myotis, Myotis lucifugus. Body mass of M. lucifugus increased during the PM period, but serum leptin levels did not change during that time. Hypothalamic mRNA levels for both the short (ObRa) and fully active long (ObRb) forms of the leptin receptor increased during PM, but the relative increase in ObRa was larger and occurred sooner than ObRb. mRNA levels of an inhibitor of leptin signaling (protein inhibitor of activated STAT3: PIAS3) increased in hypothalami during the PM period in bats. Adiponectin is an adipokine that has been linked to obesity in rodents; normally, serum levels of adiponectin decrease in obesity. In M. lucifugus, adiponectin mRNA levels decreased in adipose tissue during the period of mass gain, but circulating adiponectin levels did not change. We conclude that the relative changes in leptin receptor isoform expression during the PM fattening period may favor binding of leptin to the less active short isoform. Coupled with increased expression of PIAS3 and the dissociation of serum leptin levels from body mass and adiposity, these changes could account in part for the adaptive fattening during the PM period. In addition, the adipokine profiles of M. lucifugus during the PM period and that of obesity in non-hibernating mammals are strikingly dissimilar.     

Decreased plasma leptin levels in lean and obese Zucker rats after treatment with the serotonin reuptake inhibitor fluoxetine.

Leptin inhibits feeding, stimulates thermogenesis and decreases body weight. Serotonin reduces food intake when injected into the hypothalamus and may interact with other neurotransmitters in the control of appetite. We therefore investigated the effects of the serotonergic drug fluoxetine, which inhibits serotonin reuptake, on food intake and plasma leptin levels in lean and obese Zucker rats. Fluoxetine significantly reduced food intake in lean and obese rats, both acutely after a single injection (10 mg/kg) and during continuous subcutaneous infusion (10 mg/kg/day for 7 days). Plasma leptin levels were reduced after both 4 hours and 7 days of fluoxetine administration in lean and after 7 days in fatty rats (all p<0.01). We have previously suggested that serotonin may decrease food intake by inhibiting neuropeptide Y neurones, and we further suggest that it also inhibits leptin, possibly by an effect on white adipose tissue.     

The obesity in bilateral ovariectomized rats is related to a decrease in the expression of leptin receptors in the brain.

We investigated the expression levels of leptin receptors in the brain of ovariectomized (OVX) rats. The mean expression level of ob mRNA in adipose tissues of OVX rats was significantly (P < 0.01) lower than that in the SHAM operation group rats, and the mean body weight of OVX rats was significantly (P < 0.01) greater than that in the SHAM group rats. However, there were no differences between serum leptin concentrations in these two groups. The mean level of leptin receptor (OB-R) mRNA expression in the brain tissue and the mean level of long form type OB-R (OB-RL) mRNA expression in the hypothalamus of the OVX rats were significantly (P < 0.05) lower than those in the SHAM group rats. These changes were cancelled by supplementation with 17 beta-estradiol in OVX rats. These results suggested that not only changes in the expression level of ob mRNA in adipose tissue and the serum leptin concentration but also changes in the OB-R mRNA in the brain are involved in the body weight increase in OVX rats and that a decrease in OB-R makes transmission of signals to suppress the amount of food intake difficult, thus leading to an increase in body weight.     

Downstream migration of newly-hatched ayu (<Emphasis Type="Italic">Plecoglossus altivelis</Emphasis>) in the Tien Yen River of northern Vietnam

The ayu (Plecoglossus altivelis) is an annual, amphidromous, plecoglossid fish, distributed in Vietnam, China, Taiwan, Korea, and Japan. To date, ayu have been found only in two rivers in northern Vietnam, where little is known about their life history. The Tien Yen River is believed to be the most southwestern habitat for this species. To determine whether newly hatched ayu larvae drift and to understand their downstream migration, intensive surveys were conducted in the Tien Yen River from October to March of 2013–2016. In total, 529 drifting ayu larvae were collected from four of six sampling stations along the river. Thus, ayu reproduction has been confirmed in this river for the first time, where only adult fish had been found previously. However, we did not successfully collect larvae in the eastern branch of the river, which has a hydroelectric dam, suggesting that ayu do not inhabit this branch or else do not reproduce there. The presence of drifting larvae in the western branch from mid-December to late January implies that they spawn from late November to mid-January. Drifting larvae were captured primarily at night, but peak occurrences varied depending upon the day and the sampling station. With the range of body sizes and variable diel abundance patterns, ayu in the Tien Yen River probably employ multiple spawning grounds. This study provides fundamental life history data for the vulnerable ayu populations in northern Vietnam.     

中华蛸繁殖行为

为了解中华峭(Octopus sinensis)繁殖行为特征,通过肉眼观察及水下摄像对其行为进行研究.结果 表明,中华蛸在繁殖期有运动、捕食、求偶、交配、产卵和护卵行为.中华蛸运动依靠漏斗喷水的反作用力进行游泳和爬行;以突然袭击的方式捕食日本蟳(Charybdis japonica),繁殖后期不再进食;中华蛸具明显的求...     

Time-dependent effects of starvation on serum, pituitary and hypothalamic leptin levels in rats

Leptin is produced by white adipose tissue and other cell types and is involved in both short- and long-term appetite control. Here we studied effects of starvation on serum, pituitary and hypothalamic levels of leptin during 72 h period. Each of the starved groups was sacrificed simultaneously with the group of ad libitum fed animals. The progression of the discrete starvation response phases was monitored by testing the blood glucose, free fatty acid, urea and corticosterone levels. Starvation caused biphasic increase in corticosterone and free fatty acid levels, and significant but transient decrease in urea and glucose levels. Starvation also abolished diurnal rhythm of changes in leptin concentrations in serum and hypothalamic and pituitary tissues. Only 6 h starving period was sufficient to lock serum leptin at low levels, whereas 12 h were needed to silence leptin production/secretion in hypothalamus for the whole examined period. In contrast, leptin production by pituitary tissues of starved animals required 24 h to reach minimum, followed by full recovery by the end of starvation period. These results indicate the tissue specific pattern of leptin release and suggest that the locally produced leptin could activate its receptor in pituitary cells independently of serum levels of this hormone.     

Existence of an extra-retinal and extra-pineal photoreceptive organ that regulates photoperiodism in gonadal development of an Osmerid teleost, ayu (Plecoglossus altivelis)

Ayu (Plecoglossus altivelis) is an Osmerid teleost whose gonadal development exhibits clear photoperiodism: it is stimulated and prevented under short and long photoperiod, respectively. However, the photoreceptor organ involved in this process remains to be identified. In the present study, we examined whether gonads of ophthalmectomized (Ex) and pinealectomized (Px) ayu respond to short photoperiod to test whether photoreceptors other than lateral eyes and pineal complex are involved in the photoperiodic response of gonadal development. Gonadosomatic index (GSI) and plasma levels of sex steroids (testosterone and 11-ketotestosterone for males and testosterone and estradiol 17-beta for females) were significantly increased in the Ex+Px ayu kept under short photoperiod in both males and females as compared with the initial control. On the other hand, there were no significant increases in GSI and sex steroids in the Ex+Px ayu kept under long photoperiod. Histological observation of gonads in the Ex+Px ayu revealed that oocytes undergoing final maturation in females and proliferation of germ cells in males were observed under short photoperiod but not under long photoperiod. These results indicate that extra-retinal and extra-pineal photoreceptive organ regulates photoperiodic gonadal development in this species.     

Activation of 'immediate-early' genes by estrogen is not sufficient to achieve stimulation of DNA synthesis in rat uterus

17 beta-estradiol, a long acting estrogen that is mitogenic for rat uterus in vivo, or the short acting estrogens estriol and 16 alpha-estradiol, not mitogenic on their own, were injected into adult, castrated rats and their effect on uterine gene expression and rate of DNA synthesis were compared. All three compounds increased steady-state mRNA concentration of c-fos, c-jun and c-myc proto-oncogenes to comparable levels (2 hrs after treatment), whereas only 17 beta-estradiol was found to stimulate significantly DNA synthesis (20-22 hrs later). Based on the different retention time of the tested estrogens in rat tissues, it is concluded that a short exposure to the hormone is sufficient to render uterine cells competent to progress through the cell cycle, via activation of 'immediate-early' genes expression, but that stimulation of DNA synthesis requires further changes, achieved via a prolonged exposure of the cells to the estrogenic stimulus.     

Elevation of Striatal Dopamine Receptors by Estrogen: Dose and Time Studies

Administration to male rats of a single dose of 17 beta-estradiol valerate (8-500 micrograms/rat) or implantation of a pellet containing 17 beta-estradiol (0.5-50 mg/rat) increased serum 17 beta-estradiol levels in a dose-dependent relationship when measured on the sixth day after administration. At the same time, after these doses, the serum rat prolactin (rPRL) levels were doubled and the striatal 3,4-dihydroxyphenylethylamine (DA, dopamine) receptor densities were increased 20%. A single dose of 17 beta-estradiol valerate of 4 micrograms/rat or less did not alter serum 17 beta-estradiol or rPRL levels or the striatal DA receptor density. After the single injection of 17 beta-estradiol valerate (125 micrograms/rat) the serum 17 beta-estradiol levels peaked at 1 day, the serum rPRL levels peaked at 2 days, and the striatal DA receptor density elevation peaked from 4 to 8 days. Implantation of a pellet containing 17 beta-estradiol (25 mg/rat) produced a constant elevation of serum 17 beta-estradiol levels from 1 to 10 days. Whereas the serum rPRL levels were continuously elevated about two-fold, the densities of the striatal DA receptors were increased significantly by 20-25% only from 4 to 8 days after pellet implantation. These results indicate that striatal DA receptor density rises and returns to control levels during the constant elevation of serum 17 beta-estradiol and rPRL levels.(ABSTRACT TRUNCATED AT 250 WORDS)     

Leptin levels in menopause: effect of estrogen replacement therapy

To evaluate the effect of menopause and estrogen replacement therapy on leptin levels, 17 white postmenopausal women were recruited for the study. After an overnight fasting, blood samples were collected for LH, FSH, estradiol, testosterone, androstenedione, DHEA sulfate, insulin and leptin assays. Body mass index (BMI) and the waist-to-hip ratio were also evaluated. Patients were reanalyzed after a 12-week administration of transdermal estrogen patches delivering 50 microg 17beta-estradiol. The results were compared to those obtained from a group of 11 female volunteers in reproductive age, in whom basal blood was sampled during the early follicular phase of their cycle. Patients were divided into lean and obese according to their BMI. Obese postmenopausal women showed lower leptin levels when compared to premenopausal counterparts (25.1 +/- 5.9 vs. 37 +/- 11.3; p < 0.05), whereas no significant differences were found between the lean groups (14.5 +/- 3.8 vs. 14.4 +/- 4.9). Estrogen administration did not significantly change serum leptin concentrations in hypoestrogenized women (obese: 25.1 +/- 5.9 vs. 28. 6 +/- 9.2; lean: 14.4 +/- 4.9 vs. 17.6 +/- 7.2). A positive linear correlation was found between leptin plasma levels and BMI only in obese patients (r = 0.58; p < 0.01) both before and after estrogen treatment. Menopause is characterized by a decreased expression of the obese gene, even if estrogens do not seem to represent a main causal factor.