Efficacy of bronchial fiberscope in esophageal fistula caused by necrotizing bronchitis.

Neonatal necrotizing bronchitis is a disease that occurs in premature and low-birthweight infants who are subject to artificial respiratory management, and which has a poor prognosis, because it progresses suddenly and can result in death. There have been no reports of survival to date in cases of tracheo-esophageal fistula caused by necrotizing bronchitis, and no swift and effective management method has yet been reported. This report describes a case in which the use of a bronchial fiberscope in making an early diagnosis facilitated appropriate management and survival. The proactive use of a bronchial fiberscope in regard to this disease, which has a high fatality rate, may save lives.

Pulmonary metastasis of invasive thymoma, showing endobronchial polypoid growth: report of a case.

We report a rare case of pulmonary metastasis of invasive thymoma, with endobronchial polypoid growth causing hemosputum in a 77-year-old man. The patient had been admitted 8 years earlier for the treatment of invasive thymoma and had undergone extended thymo-thymectomy through a mid-sternotomy, followed by a course of radiotherapy. Pulmonary metastases developed 3 years after surgery, for which the patient received several courses of chemotherapy; however, the tumor continued to progress gradually. He presented at our emergency unit within 4 years of completion of the chemotherapy, with sudden massive hemoptysis. We performed endotracheal intubation to prevent suffocation and bronchoscopic examination revealed that a tumor and blood clots had obstructed the left main bronchus. We performed bronchial arterial embolization and endoscopic electrosurgery to resect the tumor, then occluded the responsible bronchus with an endobronchial Watanabe spigot to prevent further endobronchial polypoid growth and bronchial hemorrhage from the invasive thymoma.

Thymic papillo-tubular adenocarcinoma containing a cyst: report of a case.

We report a case of thymic papillo-tubular adenocarcinoma in a 55-year-old man, who had no symptoms. Sternotomy revealed a tumor in the anterior mediastinum, tightly adhered to the pericardium. It was resected completely. Interestingly, the tumor contained a unilocular cyst filled with mucinous fluid, suggesting that it originated from a pre-existing thymic cyst. Pathological examination of the tumor revealed a primary thymic papillo-tubular adenocarcinoma resembling a tumor of gut origin. Thymic adenocarcinomas, particularly of the tubular subtype, are extremely rare.

Efficacy, safety, and optimal timing of single-trocar video-assisted flexible thoracoscopic debridement under local anesthesia for complicated parapneumonic empyema.

OBJECTIVE: Thoracoscopic debridement under local anesthesia is a useful approach for complicated parapneumonic effusion or empyema (CPE) and is a less invasive procedure than video-assisted thoracoscopic surgery under general anesthesia. There are various methods of thoracoscopic debridement under local anesthesia, although the optimal timing of treatment is unknown. The objective of this study was to verify the efficacy and safety of our video-assisted flexible thoracoscopic debridement (VAFTS-D) procedure under local anesthesia, and to investigate the clinical features associated with the success of VAFTS-D. METHODS: The study included 71 consecutive patients with CPE who underwent VAFTS-D. The primary outcome was success of VAFTS-D. We retrospectively analyzed the efficacy and safety of VAFTS-D from the clinical data obtained from hospital medical records, and used univariate logistic analyses to identify potential predictors of the outcome. RESULTS: VAFTS-D was considered successful in 62 of 71 patients (87.3%). Two of the remaining nine patients died and the other seven patients required subsequent operation under general anesthesia. Complications due to VAFTS-D occurred in six patients (8.5%). Duration of empyema < 10 days (P = 0.024) and negative bacterial culture in pleural effusion (P = 0.029) were independently associated with the success of VAFTS-D by univariate logistic regression analysis. CONCLUSION: VAFTS-D might be an acceptable first-line procedure in patients with suspected CPE. VAFTS-D should be performed as early as possible for a successful outcome, and to obtain useful information on the pleural cavity.

Simultaneous resection of pulmonary tumor following cardiovascular surgery.

BACKGROUND: A pulmonary tumor is occasionally detected on a chest computed tomography (CT) scan before cardiovascular surgery. PURPOSE: In this study, we examined clinical courses of patients who had undergone the simultaneous resection of a pulmonary tumor following cardiovascular surgery. METHODS: From 2008 to 2013, 18 patients (13 men and 5 women) with a median age of 69.8 years underwent the wedge pulmonary resection for a lung tumor through a median thoracotomy following cardiovascular surgery in our hospital. Cardiovascular surgeries consisted of off-pump coronary artery bypass grafting (CABG) in six patients, aortic valve replacement and/or mitral valve plasty in 10 patients, total arch replacement in 10 patients and descending aorta replacement in 10 patients. RESULTS: No complications associated with pulmonary resections were observed. Pathological examination revealed that 15 patients (83.3%) were diagnosed with lung cancers including 13 adenocarcinomas and two squamous cell carcinomas, with the clinical stages of 1A in 13 patients, 2A in one patient and 2B in one patient. Among them, five patients received the radical pulmonary resection subsequently, whereas 10 patients were unable to receive it due to their poor cardiopulmonary function. Kaplan-Meier analysis of patients with lung cancer revealed that the 5-year survival rate and progression-free survival (PFS) rate after 3 years from the surgery were 46.2% and 73.8%, respectively. CONCLUSION: The simultaneous resection of pulmonary tumor following cardiovascular surgery is safely performed, and is useful for the pathological diagnosis of the tumor. Further studies are warranted, however, this procedure may contribute to controlling the progression of lung cancer in patients with cardiovascular disease with comorbidities.

Clinical outcome of posterior fixation surgery in patients with vertebral metastasis of lung cancer.

Vertebral metastasis of non-small-cell lung cancer (NSCLC) often leads to neurological paralysis, with deterioration of the patients' activities of daily living (ADL). Surgical treatments for the symptoms are unlikely to be recommended due to the poor prognosis of patients with advanced NSCLC. The aim of the present study was to retrospectively evaluate the clinical outcome of posterior spinal fixation surgery in patients with neurological paralysis resulting from vertebral metastasis of NSCLC. Between April, 2007 and March, 2012, 4 patients (3 men and 1 woman; median age, 56.5 years) underwent fixation surgery at the Shiga University of Medical Science Hospital (Otsu, Japan). The mean preoperative Tokuhashi and Tomita scores of the patients were high (8.25 and 7.0, respectively). However, the Frankel grade functional score and performance status of the patients improved following fixation surgery, after which all patients received chemoradiotherapy. Postoperatively, the median paralysis-free time was 41 months (range, 17-42 months) and the median survival time was 42.5 months (range, 22-43 months). According to the functional scores, the patients had a poor prognosis, which may have been a contraindication for fixation surgery. In these cases, however, surgical treatment improved the patients' ADL and increased the likelihood of receiving anticancer therapy, contributing to the prolongation of survival. Therefore, fixation surgery may be beneficial for patients with neurological paralysis following vertebral metastasis of advanced NSCLC.

Novel fish hypothalamic neuropeptides stimulate the release of gonadotrophins and growth hormone from the pituitary of sockeye salmon.

We recently identified a cDNA encoding three novel fish hypothalamic neuropeptides, having LPXRF-NH(2) from the goldfish brain. In this study, to clarify the physiological functions of these three LPXRFamide peptides (gfLPXRFa-1, -2, and -3), we analysed the localisation and hypophysiotrophic activity of these peptides using sockeye salmon, Oncorhynchus nerka, in which immunoassay systems for several anterior pituitary hormones have been developed. gfLPXRFa-immunoreactive cell bodies were detected in the nucleus posterioris periventricularis of the hypothalamus and immunoreactive fibres were distributed in various brain regions and the pituitary. We also detected gfLPXRFa-immunoreactivity in the pituitary by competitive enzyme-linked immunosorbent assay combined with reversed-phase HPLC. These three gfLPXRFamide peptides stimulated the release of FSH, LH and GH, but did not affect the release of prolactin (PRL) and somatolactin (SL) from cultured pituitary cells. These results suggest that novel fish hypothalamic LPXR-Famide peptides exist in the brain and pituitary of sockeye salmon and stimulate the release of gonadotrophins and GH from the pituitary.

Different gene expression profiles between normal and thermally selected strains of rainbow trout, Oncorhynchus mykiss, as revealed by comprehensive transcriptome analysis.

A high-temperature selected (HT) strain of rainbow trout was established from the Donaldson (DS) strain by traditional selective breeding in Japan. The aim of this study is to investigate genes related to upper temperature tolerance in this strain utilizing next generation sequencer (NGS), and to establish comprehensive and comparable datasets in brain, liver, muscle, heart and gill tissues between the HT and DS strains. After assembling, clustering and filtering, 242,530 contigs were obtained. Among them, 7624 transcripts had at least 10 counts in expression analysis in all tissues and used as references. BLASTX homology search showed that 7329 transcripts matched with known genes. Compared to the DS strain, the HT strain expressed 90, 775, 349, 188 and 194 genes 2 folds or more in brain, liver, muscle, heart, and gill, respectively in the case of fish before heat-exposure treatment. Meanwhile, the HT strain expressed 292, 363, 433, 322 and 211 genes 2 folds or more in brain, liver, muscle, heart, and gill, respectively in case of fish after heat-exposure treatment. Many of heat shock protein family genes and transcription factor AP-1 related genes were highly expressed in all tissues of the HT strain compared with the DS strain. These results suggest that these genes play key roles in upper temperature tolerance. These comprehensive and comparable datasets will offer broad visions for upper temperature tolerance in fish species.

Effects of melatonin feeding on smoltification in masu salmon (Oncorhynchus masou).

Influences of photoperiod on plasma melatonin profiles and effects of melatonin administration on long-day-induced smoltification in masu salmon (Oncorhynchus masou) were investigated in order to reveal the roles of melatonin in the regulation of smoltification in salmonids. Under light-dark (LD) cycles, plasma melatonin levels exhibited daily variation, with higher values during the dark phase than during the light phase. The duration of nocturnal elevation under short photoperiod (LD 8:16) was longer than that under long photoperiod (LD 16:8). Melatonin feeding (0.01, 0.1 and 1 mg/kg body weight) elevated plasma levels of melatonin in a dose-dependent manner for at least 7 h but not for 24 h. When masu salmon reared under short photoperiod were exposed to long photoperiod (LD 16:8) and fed melatonin (1 mg/kg body weight) 7 hours before the onset of darkness, a significantly smaller proportion of smolts appeared in the melatonin-fed group after 32 days than in the control group. However, after 59 days of the treatment, there was no difference in the proportion of smolts between the control and melatonin-treated groups. Thus, melatonin feeding mimicked the effects of short photoperiod, which delays but does not completely suppress smoltification. These results indicate that the day length is transduced into changes in the duration of nocturnal elevation in plasma melatonin levels, and that artificial modification of the plasma melatonin pattern possibly delays the physiological processes of smoltification induced by long-day photoperiodic treatment.

Daily variations in melatonin binding sites in the masu salmon brain.

Daily variations in melatonin binding sites in the brain of underyearling masu salmon Oncorhynchus masou were examined by radioreceptor assay using 2-[125I]iodomelatonin as the radioligand. Fish were reared under a natural photoperiod in July and sampled eight times at 3 h intervals from 12:00 to 09:00 h. Plasma melatonin levels showed robust daily rhythms in both precocious males and immature females, with high and low levels during night and day, respectively. The affinity (Kd) and density (Bmax) of melatonin binding sites in the brain also showed similar variations. There were significant positive correlations between the plasma melatonin levels and the Kd or the Bmax in immature females and between the Kd and Bmax values in both precocious males and immature females. These results indicate that melatonin binding sites in the brain showed daily variations under a natural photoperiod in masu salmon.

Disturbance of plasma melatonin profile by high dose melatonin administration inhibits testicular maturation of precocious male masu salmon.

We have previously shown that the testicular development of underyearling male masu salmon Oncorhynchus masou reared under a long photoperiod was accelerated by oral melatonin treatment (0.5 mg melatonin/kg body weight/day), suggesting that melatonin mediates photoperiodic signaling. In this study, we further examined the effects of a disturbance in the plasma melatonin profile on gonadal development in underyearling male masu salmon by administering a higher dose of melatonin. Fish randomly selected in June were divided into two groups. They were reared under a light:dark (LD) cycle of 16:8 (lights on 04:00-20:00 hr) and fed with pellets sprayed with melatonin or vehicle twice a day at 08:30 and at 15:30 hr (7.5 mg melatonin/kg body weight/day) until October. Fish were sampled on Day 0, 25, 60, 90 and 120. The plasma melatonin levels were high in the dark phase and low in the light phase in the control group, while they were constantly high with no significant change in the melatonin-treated group. Melatonin treatment had inhibitory effects on the gonadosomatic index and plasma testosterone levels. Pituitary salmon gonadotropin-releasing hormone content and luteinizing hormone content were significantly lower in the melatonin-treated group on Day 60 and 90, respectively. These results indicate that the plasma melatonin profile is important for mediating photoperiodic signals that regulate brain-pituitary-gonadal axis in underyearling precocious male masu salmon.

Inhibition of transforming growth factor-ß release from tumor cells reduces their motility associated with epithelial-mesenchymal transition.

The high level of transforming growth factor­ß (TGF­ß) in tumor tissue, which is primarily released from tumor cells, helps maintain their metastatic nature and exacerbates the creation of a pro-tumor microenvironment. Although the strategy of targeting TGF­ß in cancer therapy has shown promise, its effects remain limited. In the present study, we focused on tumor cells as sources of TGF­ß release, and hypothesized that inhibition of their TGF­ß release could suppress their epithelial-mesenchymal transition (EMT)-associated metastatic nature and inactivate the induction of suppressor immune cells. To investigate this hypothesis, LLC1 cells, a mouse lung cancer cell line, were cultured with the TGF­ß release inhibitor tranilast and the motility of LLC1 cells was examined. Furthermore, to examine whether inhibition of TGF­ß release influences the induction of regulatory T (Treg) cells, spleen cells from normal mice were cultured in medium in which LLC1 cells had been cultured with tranilast. The results showed that tranilast inhibited the release of TGF­ß1 from LLC1 cells without affecting their proliferation. Inhibition of TGF­ß1 release suppressed the invasive activity of LLC1 cells, but enhanced their activity to adhere. mRNA levels of Slug and Twist were decreased in LLC1 cells, whereas levels of E­cadherin were recovered. Treg cells were less frequently induced by medium in which LLC1 cells had been cultured with tranilast. Taken together, inhibition of TGF­ß1 release dampens the metastatic nature of LLC1 cells through the downregulation of EMT and possesses the possibility to improve antitumor immune responses through suppression of Treg cell induction. These findings provide a new rationale for development of TGF­ß­targeted molecular immunotherapy against cancer.

Tracheo-brachiocephalic artery fistula after tracheostomy associated with thoracic deformity: a case report.

INTRODUCTION: Tracheo-brachiocephalic artery fistulae are critical long-term complications after tracheostomy, reported in 0.6% of patients within three to four weeks after the procedure. In 30% to 50% of cases there is some bleeding prior to onset. Since the onset involves sudden massive bleeding, the prognosis is poor; the reported survival rate is 10% to 30%. The direct cause of bleeding is the formation of a fistula with the trachea subsequent to arterial injury by the tracheostomy tube. Endo-tracheal factors are movement of the tracheostomy tube due to body movement and seizures, pressure exerted by the cuff of the tracheostomy tube, tracheostomy at lower levels, and the fragility of blood vessels and the trachea due to steroid or radiation therapy, and malnutrition. Extra-tracheal factors include prior surgery and deformity and shifting of the trachea and major blood vessels due to congenital kyphoscoliosis or thoracic deformity. There has been no report of the usefulness of contrast-enhanced computed tomography studies to identify the anatomical relationship between the trachea and brachiocephalic artery. CASE PRESENTATION: A 27-year-old Mongolian woman with congenital muscular dystrophy who underwent tracheal intubation for airway management due to pneumonia and granulation development developed a tracheo-brachiocephalic artery fistula during the placement of the tracheostomy tube. It was diagnosed by contrast-enhanced chest computed tomography and repaired. About a month later she developed massive airway bleeding during replacement of the tracheostomy tube. Temporary hemostasis was achieved by compression via cuff inflation. A contrast-enhanced chest computed tomography scan demonstrated a narrowed brachiocephalic artery running along and ventral to the tube and a tracheo-brachiocephalic artery fistula was suspected. She underwent brachiocephalic artery resection and aorta, right common carotid artery, and subclavian artery bypass surgery with an innominate vein, tracheoplasty, and partial sternectomy. We noted marked thoracic deformity; the brachiocephalic artery was compressed by the trachea and chest wall resulting in localized wall necrosis and the development of a tracheo-brachiocephalic artery fistula, a fatal complication whose prevention is important. CONCLUSIONS: We suggest that before tracheostomy, the anatomic relationship between the trachea and brachiocephalic artery must be confirmed by contrast-enhanced chest computed tomography scan.

Effects of a gonadotropin-releasing hormone antagonist on gonadotropin levels in Masu salmon and Sockeye salmon.

The salmon gonadotropin-releasing hormone (sGnRH) is considered to be involved in gonadal maturation via gonadotropin (GTH) secretion in salmonid fishes. However, there is no direct evidence for endogenous sGnRH-stimulated GTH secretion in salmonids. In this study, to clarify whether endogenous sGnRH stimulates GTH secretion, we examined the effects of the mammalian GnRH (mGnRH) antagonist [Ac-Delta(3)-Pro(1), 4FD-Phe(2), D-Trp(3,6)]-mGnRH on luteinizing hormone (LH) levels in 0-year-old masu salmon Oncorhynchus masou and sockeye salmon Oncorhynchus nerka. First, the effects of the GnRH antagonist on LH release were examined in 0-year-old precocious male masu salmon. GnRH antagonist treatment for 3 hr significantly inhibited an increase in plasma LH levels that was artificially induced by exogenous sGnRH administration, indicating that the GnRH antagonist is effective in inhibiting LH release from the pituitary. Subsequently, we examined the effect of the GnRH antagonist on LH synthesis in 0-year-old immature sockeye salmon that were pretreated with exogenous testosterone for 42 days to increase the pituitary LH contents; the testosterone treatment did not affect the plasma LH levels. GnRH antagonist treatment slightly but significantly inhibited an increase in the testosterone-stimulated pituitary LH content levels. However, no significant differences in the plasma LH levels were observed between the GnRH antagonist-treated and control groups. These results suggest that endogenous sGnRH is involved in LH secretion in salmonid fishes.

Effects of growth hormone and cortisol on the downstream migratory behavior in masu salmon, Oncorhynchus masou.

The effects of ovine growth hormone (oGH) and cortisol on downstream migratory behavior in yearling (1(+)) smolts and underyearling (0(+)) parr of masu salmon, Oncorhynchus masou, were examined during the downstream migratory period in spring using artificial raceways. In May, each of 22 1(+) smolts and 0(+) parr were implanted with cholesterol pellets containing 250 microg of oGH and/or 2 mg of cortisol. Their downstream migratory behavior was subsequently observed in artificial raceways, along with control groups 4-23 days after implantation. In 1(+) smolts, the frequency of downstream migratory behavior was 23%, 18%, 72%, and 82% in the control, oGH, cortisol, and oGH+cortisol-treated groups, respectively. The frequency was significantly higher in the cortisol and oGH+cortisol-treated groups than in the control and oGH-treated groups. In 0(+) parr, the frequency of downstream migratory behavior in the cortisol (82%) and cortisol+oGH-treated (90%) groups was significantly higher than in the control (18%) and oGH-treated (0%) groups. These results indicate that cortisol is an important endocrine factor inducing downstream migratory behavior in both 1(+) smolt and 0(+) parr of masu salmon.

Lack of circadian regulation of in vitro melatonin release from the pineal organ of salmonid teleosts.

In many teleost species, the photoreceptive pineal organ harbors the circadian clock that regulates melatonin release in the pineal organ itself. However, the pineal organ of three salmonids (rainbow trout Oncorhynchus mykiss, masu salmon Oncorhynchus masou, and sockeye salmon Oncorhynchus nerka) did not exhibit circadian rhythms in melatonin release when maintained under constant darkness (DD) in vitro, suggesting that the pineal organs of all salmonids lack the circadian regulation of melatonin production. To test this hypothesis, the pineal organ of seven salmonids (common whitefish Coregonus lavaretus, grayling Thymallus thymallus, Japanese huchen Hucho perryi, Japanese charr Salvelius leucomaenis pluvius, brook trout Salvelius fontinalis, brown trout Salmo trutta and chum salmon Oncorhynchus keta) and closely related osmerids (ayu Plecoglossus altivelis altivelis and Japanese smelt Hypomesus nipponensis) were individually maintained in flow-through culture at 15 degrees C under several light conditions. Under light-dark cycles, the pineal organ of all species showed a rhythmic melatonin release with high rates during the dark phase. Under DD, the osmerid pineal organs exhibited circadian rhythms in melatonin release with high rates only during the subjective-night but the salmonid pineal organs constantly released melatonin at high rates. Under constant light, melatonin release was suppressed in all species. The pineal organ of rainbow trout maintained at different temperature (15, 20 or 25 degrees C) under DD released melatonin with high rates but the amount of melatonin released was temperature-sensitive (highest at 20 degrees C). Thus, melatonin release from the pineal organ of osmerids is regulated by both light and circadian clock but the circadian regulation is lacking in salmonids. These results indicate that ancestral salmonids lost the circadian regulation of melatonin production after the divergence from osmerid teleosts.

Changes in melatonin binding sites under artificial light-dark, constant light and constant dark conditions in the masu salmon brain.

To test whether the affinity (Kd) and total binding capacity (Bmax) of melatonin receptors exhibit daily and circadian changes in teleost fish whose melatonin secretion is not regulated by intra-pineal clocks, we examined the changes in melatonin binding sites in the brains of underyearling masu salmon Oncorhynchus masou under artificial light-dark (LD), constant light (LL) and constant dark (DD) conditions. In Experiment 1, fish were reared under a long (LD 16:8) or short (LD 8:16) photoperiod for 69 days. Blood and brains were sampled eight times at 3 h intervals. Plasma melatonin levels were high during the dark phase and low during the light phase in both photoperiodic groups. The Bmax exhibited no daily variations. Although the Kd slightly, but significantly, changed under LD 8:16, this may be of little physiological significance. In Experiment 2, fish reared under LD 12:12 for 27 days were exposed to LL or DD from the onset of the dark phase under LD 12:12. Blood and brains were sampled 13 times at 4 h intervals for two complete 24 h cycles. Plasma melatonin levels were constantly high in the DD group and low in the LL group. No significant differences were observed in the Kd and the Bmax between the two groups, and the Kd and the Bmax exhibited no circadian variation either in the LL or DD groups. These results indicate that light conditions have little effect on melatonin binding sites in the masu salmon brain.

L-Kynurenine, an amino acid identified as a sex pheromone in the urine of ovulated female masu salmon.

Many animals employ sex pheromones to find mating partners during their reproductive seasons. However, most sex pheromones of vertebrates remain to be identified. Over the past 20 years, steroids and prostaglandins have been identified as sex pheromones in several fishes. These pheromones are broadly termed "hormonal pheromones" because they or their precursors act as hormones in these fishes. Hitherto, no other type of sex pheromone has been unambiguously identified in teleost fish. Here we report the identification of a "nonhormonal pheromone" in teleost fish. The urine of the reproductively mature female masu salmon (Oncorhynchus masou) contains a male-attracting pheromone. Bioassay-guided fractionation yielded an active compound that was identical to L-kynurenine in spectral and chromatographic properties. L-Kynurenine is a major metabolite of L-tryptophan in vertebrates. This pheromone elicits a male-specific behavior at even picomolar concentrations; its electrophysiological threshold is 10(-14) M. L-Kynurenine is a reasonable substance for female masu salmon to advertise their readiness for mating.

Characterization and maturational differences of melatonin binding sites in the masu salmon brain.

To obtain a better understanding of the roles of melatonin in the mediation of photoperiodic signaling, we have examined the pharmacological characteristics, guanine nucleotide modulation, and maturational differences of melatonin binding sites in the brain of masu salmon Oncorhynchus masou by radioreceptor assay using 2-[125I]iodomelatonin as the radioligand. The specific binding of 2-[125I]iodomelatonin was rapid, stable, saturable, and reversible. Saturation experiments demonstrated that 2-[125I]iodomelatonin binds to a single class of receptor sites with an affinity constant (K(d)) of 6.3+/-0.5 pM and a total binding capacity (B(max)) of 15.18+/-0.22 fmol/mg protein in underyearling precocious males in July. Competition experiments revealed that the binding sites are highly specific for melatonin and related analogues. Treatment with guanosine 5(')-O-(3-thiotriphosphate) significantly reduced the specific binding, indicating that melatonin binding sites in the masu salmon brain are coupled to G protein. Significant differences were seen in B(max), but not K(d), among the fish groups differing in maturity. In the underyearling fish in July, the B(max) of precocious males and immature males was significantly higher than that of immature females. Then, the B(max) of precocious males decreased in October, when the fish spermiated. In the 2-year-old fish, B(max) was significantly higher in spermiating males than ovulated females. These results indicate that melatonin plays neuromodulatory roles in the central nervous system through specific receptors. Furthermore, gonadal maturation affects the density of melatonin binding sites in the masu salmon brain by an unknown mechanism.