Effects of different doses and durations of melatonin infusions on plasma melatonin concentrations in pinealectomized Syrian hamsters: Consequences at the level of sexual activity

The effect of different doses and durations of melatonin infusions on plasma melatonin concentrations has been studied in pinealectomized Syrian hamsters maintained under short photoperiod at either 7 degrees C or 18 degrees C. The effects of the infusions on plasma melatonin concentrations and on gonadal activity were compared. The results show that the minimal effective quantity of infused melatonin that induced gonadal atrophy was 40 ng/h at 7 degrees C and 20 ng/h at 18 degrees C. An infusion of 8 hr duration per day is necessary to inhibit sexual activity, while an infusion of 6 hr duration was ineffective. This finding suggests that the critical duration of melatonin infusion is between 6 and 8 hr. Despite the various doses of melatonin infused, plasma melatonin concentrations measured in the middle of the infusion period did not differ significantly from concentrations measured in intact animals. This finding suggests that the metabolism of infused melatonin increases as the dose of melatonin increases. Moreover, the different physiological effects observed after the various melatonin infusions cannot be explained by variations in plasma melatonin concentrations.     

New sensitive serum melatonin radioimmunoassay employing the Kennaway G280 antibody: Syrian hamster morning adrenergic response

Abstract: A new procedure with the G280 antibody of Kennaway provides an assay for circulating melatonin (aMT) with a sample volume (200 μl), an analytic (0.33 pg/ml) and functional (0.62–0.80 pg/ml) detectability, a 50% displacement dose (6.4 pg/ml), a Kd (0.657 pM), and measured circulating daytime levels lower than reported for previous procedures, and 100% assay recovery. The normal daytime range in adult human and Syrian hamster serum was 0.4–4 pg/ml. The pattern of fall of the nocturnal surge of Syrian hamster serum aMT near the time of lights-on was unaltered by extended darkness. Isoproterenol (ISO) injection 1 hr after lights-on, when aMT had reached daytime levels, raised serum and pineal aMT dramatically 2 hr postinjection. The same dose of ISO injected 4 hr into light produced only a small detectable increase. Novel extension of nocturnal darkness did not affect the responses to ISO. Thus, when they are allowed to occur at the usual time on a 10-hr dark schedule, both the fall from the nocturnal aMT surge and the subsequent loss of pineal beta-adrenergic responsiveness in this species occur endogenously (probably entrained) rather than from gating by acute effects of morning light. Changes in daytime serum aMT consistent with concomitant changes in the pineal can be measured with a sufficiently sensitive radioimmunoassay.     

Coexpression of MT1 and RORalpha1 melatonin receptors in the Syrian hamster Harderian gland

Melatonin acts through several specific receptors, including membrane receptors (MT(1) and MT(2)) and members of the RZR/ROR nuclear receptors family, which have been identified in a large variety of mammalian and nonmammalian cells types. Both membrane and nuclear melatonin receptors have been partially characterized in Harderian gland of the Syrian hamster. Nevertheless, the identities of these receptors were unknown until this study, where the coexistence of MT(1) and RORalpha(1) in this gland was determined by nested RT-PCR followed by amplicon sequencing and Western-blot. Furthermore, the cellular localization of both receptors was determined by immunohistochemistry. Thus, MT(1) receptor was localized exclusively at the basal side of the cell acini, supporting the hypothesis that this receptor is activated by the pineal-synthesized melatonin. On the contrary, although a RORalpha(1)-immunoreactivity was observed in nuclei of epithelial cells of both sexes, an extranuclear specific staining, which was more frequently among those cells of males, was also seen. The implication of this possible nuclear exclusion of RORalpha(1) on the role of this indoleamine against oxidative stress is discussed.     

Regulation of the androgen receptors in the Harderian gland of the male Syrian hamster: Influence of photoperiod, castration, and chronic melatonin treatment

Male Syrian hamsters that were exposed for 8 weeks to short photoperiod (LD 10:14) or treated with melatonin in the late afternoon under long photoperiod conditions (LD 14:10) had a significantly higher content of androgen receptors in the Lipidex-purified soluble fractions isolated from the Harderian glands as compared to the long photoperiod (LD 14:10) exposed controls. Simultaneous computer-assisted analyses of all series of saturation and competition experiments revealed that the numerical value of the apparent Kd, as determined by using the synthetic androgen R-1881 (methyltrienolone), was not different between the experimental groups, and ranged from 0.050 to 0.067 nM. Of the principal natural androgens, testosterone (T) was most potent in inhibiting methyltrienolone binding to the receptor (Ki values from 0.33 to 0.55 nM), and 5 alpha-dihydrotestosterone (DHT) and delta 4-androstenedione (AD) were less effective (Ki values between 1 and 1.9 nM). In the hypothalami and pituitaries of the same animals, used in parallel control assays, DHT was twice as potent as T. Short-term castration (24 hr post-orchidectomy) did not result in significant changes in the receptor binding characteristics. Following 8 weeks exposure to a long photoperiod (LD 14:10) the Bmax values demonstrated a four-fold increase in castrated animals (179 fmoles/mg protein vs. 47 fmoles/mg protein) over intact controls. The relative binding affinity of the major androgens under these conditions remained unchanged, with the exception of AD, where a five-fold increase in the numerical Ki values (decrease in the binding affinity) was recorded (Ki = 9.6 nM).(ABSTRACT TRUNCATED AT 250 WORDS)     

Vasoactive intestinal peptide stimulates N-acetyltransferase and hydroxyindole-O-methyltransferase activities and melatonin production in cultured rat but not in Syrian hamster pineal glands

The purpose of this study was to compare the responses of the Syrian hamster and rat pineal glands in organ culture to vasoactive intestinal peptide (VIP). The endpoints in these studies were the activities of pineal N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT), as well as pineal and medium melatonin levels. When rat pineal glands were incubated with either VIP (1 microM) or isoproterenol (1 microM), a beta-adrenergic agonist, a significant increase in NAT and HIOMT activities and melatonin levels were observed within 3 hr. Conversely, during the day, VIP (1 microM) was ineffective in stimulating these parameters in hamster pineal gland after incubation times of either 2, 4, 6, or 8 hr. In another experiment, hamster pineal glands were collected from animals killed in the late dark period (after 30 min light exposure). In these glands, isoproterenol promoted NAT activity and melatonin production; however, VIP was ineffective in stimulating either NAT or HIOMT activities; likewise, VIP had no stimulatory effect on pineal melatonin levels at night. Finally, when hamster pineal glands at night were incubated with either 0, 10 nM, 100 nM, 10 microM, or 100 microM VIP, no changes in any parameter of melatonin synthesis were measured. The results indicate that the hamster pineal gland, unlike that of the rat, may not respond to VIP with an increased melatonin production.     

Chronic administration of melatonin induces changes in porphyrins and in the histology of male and female hamster Harderian gland: Interrelation with the gonadal status

In this paper, we have investigated the influence of melatonin on the histology and porphyrin content of the Syrian hamster Harderian glands. Daily afternoon injections of 25 micrograms of melatonin to female hamsters for 12 weeks resulted in the discontinuity of estrous cyclicity, a marked decrease in the Harderian gland intraluminal area occupied by porphyrins, and in a significant rise in the number of Type II cells. A similar decrease in porphyrins was observed after 8 weeks of ovariectomy. However, if the melatonin injections were given for only 8 weeks (without inducing gonadal atrophy), no changes were observed in the area occupied by intraluminal porphyrins, suggesting that the effects of melatonin in female Syrian hamsters might be associated with the subsequent gonadal atrophy. Castration of male hamsters induced a significant increase in porphyrins and a clear drop in the number of Type II cells. These changes were totally prevented when melatonin was administered daily from the day of castration. Our results suggest that melatonin, at least in male Syrian hamsters, plays a role in Harderian metabolism, acting directly on the Harderian secretory cells or indirectly through pituitary hormones.     

Role of extracellular calcium on the regulation of melatonin synthesis in the Syrian hamster pineal gland

The role of extracellular calcium on the induction of cyclic AMP production, N-acetyltransferase (NAT) activity and melatonin synthesis, induced by forskolin, was investigated in Syrian hamster pineal glands. Pineals were removed from hamsters killed either in the first half of the normal dark period or late in the dark period. Forskolin immediately increased NAT activity and melatonin levels only when the glands were collected late in the dark period, while in the first half of the dark phase, hamster pineals responded to forskolin with an increase of NAT activity and melatonin production only after 6 hr of incubation. The absence of calcium prevented the induction of melatonin synthesis by forskolin only when glands were collected early in the dark phase and incubated for 6 hr. In the second half of the normal dark period removal of calcium markedly decreased NAT activity and melatonin levels in glands incubated with forskolin for either 4 or 6 hr. However, the absence of extracellular calcium had no significant effect on the induction of cyclic AMP production by forskolin in pineals collected either early in the dark period or late in the dark phase. These data indicate that at least part of the action of extracellular calcium is indirect and that it affects steps in the induction of melatonin synthesis beyond the accumulation of cAMP.     

Pineal Dependence of the Syrian Hamster''s Nocturnal Serum Melatonin Surge

The usual nocturnal surge of pineal melatonin content was blocked by bilateral superior cervical ganglionectomy in male Syrian hamsters. Ganglionectomy and pinealectomy each prevented the nocturnal rise of serum melatonin concentration seen in control animals. The normal nocturnal surge of circulating melatonin in this species appears to depend on the pineal gland and its sympathetic innervation.     

Pineal melatonin concentrations in the Syrian hamster

Pineal melatonin concentrations exhibited a marked diurnal rhythmicity in gold hamsters maintained in a light-dark cycle of 15 h of light and 10 h of darkness. When tissue was collected at 3-h intervals throughout a 24-h period, daytime levels of 95--232 pg/pineal gland rose to concentrations of 760--1335 pg/pineal gland (P greater than 0.001 vs. all other values) at 0400 h, 8 h after the onset of darkness. When tissue was collected sequentially during the dark phase, pineal melatonin concentrations remained significantly elevated from 0200--0500 h (P less than 0.01 and P less than 0.001 vs. daytime values, respectively). Superior cervical ganglionectomy abolished the rhythm of pineal melatonin concentrations, and the concentrations were maintained at 60--105 pg/pineal gland throughout a 24-hr period.     

果糖联合高脂饮食对金黄地鼠糖脂代谢的影响

目的通过果糖或葡萄糖联合高脂饮食喂养叙利亚金黄地鼠,比较不同饮食成分喂养对地鼠糖脂代谢的不同影响。方法将金黄地鼠随机分成正常对照组（NC）、高脂组（HF）、果糖高脂组（FRU＋HF）、葡萄糖高脂组（Glu＋HF）,喂养12周,测定体重、血脂、血糖、胰岛素、肝指数,观察肝脏及胰腺形态及组织学变化。结果各高脂喂养组地鼠与对照组比较TC、TG、血糖、LDL-C、HDL-C、肝指数升高,胰岛素水平降低,肝脂肪样变,胰岛增生,其中FRU＋HF组TG、胰岛素敏感性降低,肝指数升高,肝及胰岛病理变化更明显（P〈0．05）。结论果糖高脂喂养的金黄地鼠模型特点为TG显著增高、糖耐量减低、胰岛素抵抗及脂肪肝,更适合作为现代人高果糖高脂饮食导致糖脂代谢紊乱的研究模型。     

Changes with age in daytime and nighttime contents of melatonin, indoleamines, and catecholamines in the pineal gland: A comparative study in rat and Syrian hamster

Abstract: Previous studies in rodents showed a severe deterioration of pineal physiology with aging. The present study investigated the age-related changes in the content of monoamines and metabolites in rat and Syrian hamster pineal gland. In addition to melatonin, the levels of 5-hydroxytryptophan (5HTP), serotonin (5HT), 5-hydroxyindoleacetic acid (5HIAA), N-acetylserotonin (N-Ac-5HT), dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), and noradrenaline (NA) were measured by HPLC. Pronounced reductions were found in 5HT and 5HIAA contents during daytime in rats of 24 months, which had not been observed in animals of 12 months. In addition, nighttime pineal 5HIAA, N-Ac-5HT, and melatonin contents were decreased in the old rats, although a significant day: night variation persisted. Also a diurnal fluctuation in NA, DA, and DOPAC contents was present in young and middle-aged rats but not for NA and DOPAC in the oldest rats due to a decrease in the nighttime levels. Pineal DA levels were also reduced in 24-month-old rats during the night, although a marked day: night change was still found. In the Syrian hamster pineal, significant reductions in daytime 5HT and 5HIAA were found respectively at 12 and 18 months, while nighttime levels of these compounds were decreased from 18 months. The nocturnal content of N-Ac-5HT dropped gradually from 12 months, and melatonin was reduced by 74% and 86% in hamsters of 18 and 24 months, respectively. In all these compounds, a significant day: night variation was observed irrespective of age. However, neither a day: night variation nor an effect of aging was found in terms of pineal NA content. In contrast, pineal DA and DOPAC levels displayed a diurnal variation in hamsters of 1.5 and 6 months, but not in animals of 12 and 18 months due a reduced nighttime content. These data suggest that the decline of pineal melatonin with age is a consequence of a deficit in the pathway of serotonin utilization. This probably is explained by a reduced N-acetyltransferase activity, which may be linked to impaired pineal catecholaminergic neurotransmission.     

Gastric metabolism of ethanol in Syrian golden hamster

First-pass metabolism (FPM) of orally ingested alcohol has been attributed to gastric alcohol dehydrogenase (ADH) activity in both humans and rats. To determine whether gastric alcohol dehydrogenase is essential for alcohol FPM, we sought a species lacking this enzyme. We found that Syrian golden hamsters have negligible gastric ADH yet alcohol FPM (265±25 mg ethanol/kg) was comparable to that of rats (251±31 mg/kg). To determine whether hamster gastric mucosal cells metabolize sufficient alcohol to account for this FPM, primary cultures were established, and these cells metabolized 1.99±0.84 mol ethanol/10⁶ cells/hr, an amount sufficient to account for the bulk of alcohol FPM. In contrast to alcohol dehydrogenase, catalase activity in hamster gastric mucosa (870±93 units/g tissue) was eightfold higher than in rat gastric mucosa (111±9 units/g tissue;P<0.0001). FPM in hamsters treated with 3-aminotriazole was reduced from 242±24 to 130±22 mg/kg (P<0.05) but was not reduced in rats. The results imply that catalase participates in gastric alcohol metabolism of hamsters.Supported by NIH grants AA03508 and AA07275 and the Department of Veteran Affairs.     

Attenuated nocturnal rise in pineal and serum melatonin in a genetically cardiomyopathic Syrian hamster with a deficient calcium pump

Day and nighttime melatonin production in the pineal gland was compared in normal and cardiomyopathic (polydystrophic) adult male Syrian hamsters. These strains of hamsters were selected for comparison because the cardiomyopathetic hamster displays a deficient transmembrane Ca(2+)-pump in a number of tissues, and intracellular CA2+ concentrations ([Ca2+]i) play a central role in the nocturnal increase in pineal melatonin synthesis. Daytime levels of all constituents measured, i.e., pineal N-acetyltransferase (NAT) activity, pineal and serum melatonin levels, and pineal 5-hydroxytryptophan (5-HTP), serotonin, and 5-hydroxyindole acetic acid (5-HIAA) contents, were comparable in control and dystrophic hamsters. In contrast, the nighttime rises in pineal NAT activity and pineal and serum melatonin levels were significantly attenuated in the dystrophic hamsters. By comparison, the pineal contents of 5-HTP, serotonin, and 5-HIAA were essentially the same in both groups of hamsters with both pineal serotonin and 5-HIAA values exhibiting the usual nighttime drop. It is presumed that the alterations in nocturnal melatonin production in the pineal gland of the cardiomyopathic hamster may relate to a generalized deficiency in the Ca(2+)-pump in pinealocyte plasma membranes, which leads to unusually high [Ca2+]i, causing a depression of NAT activity; this leads to the commensurate decline in pineal and serum melatonin levels. Harderian gland NAT activity and melatonin levels were essentially similar in the two groups of animals, although NAT activity was slightly depressed in the dystrophic hamsters killed during the day. The reduced amounts of intrascapular brown fat in the cardiomyopathic hamster is speculated to be a result of the diminished amount of melatonin produced in these animals.     

Beneficial properties of melatonin in an experimental model of pancreatic cancer

Pancreatic cancer is a major health problem because of the aggressiveness of the disease and the lack of effective systemic therapies. Melatonin has antioxidant activity and prevents experimental genotoxicity. However, the effect of melatonin in pancreatic cancer has not been tested. Pancreatic carcinogenesis was induced by N-nitrosobis (2-oxopropyl)amine (BOP) in Syrian hamsters. Melatonin was administered during the BOP-induction phase (12 wk) and/or following the postinduction phase (12 wk). Different parameters of oxidative stress including lipid peroxides (LPO) and antioxidants (superoxide dismutase, catalase, reduced glutathione and glutathione peroxidase) were determined in pancreatic tissue. Also, the presence of atypical hyperplasia (AH), well and moderately differentiated adenomacarcinoma (ADC-WD and ADC-MD, respectively) were studied. The administration of BOP induced an intense oxidative stress and ADC induction in the pancreas. The administration of melatonin during the induction or postinduction phase reduced LPO and improved the antioxidant status, as well as drastically reducing the presence of ADC but some AH remained. In conclusion, treatment with melatonin reduced oxidative damage and cancer nodules induced by BOP in the pancreas.     

Time-dependent effects of melatonin on immune measurements in male Syrian hamsters

Abstract: Adult, male Syrian hamsters received daily subcutaneous melatonin (25 μg) injections or vehicle injections at 08:00 or 17:00 hr for 11 weeks. Body weights were measured weekly throughout the experiment and testes weights, spleen weights, and serum was collected at the end of the experiment. The spleens were sectioned and immunocytochemically analyzed for immunoglobulin G and serum levels of interferon-gamma, interleukin-2, and interleukin-4 were determined in heterologous mouse assays. Melatonin injections at 17:00 hr, but not at 08.00 hr, increased body weights, decreased testes weights and serum testosterone levels, and had no effect on immunoglobulin G content in the spleen. Likewise, melatonin injections at 17:00 hr, but not at 08:00 hr, increased serum interferon-gamma levels, had no effect on interleukin-2 levels, and appeared to increase interleukin-4 levels. Since melatonin injections at 08:00 hr were ineffective in altering immune measurements and correlations between reproductive measures and immune measures were high, the most parsimonious explanation for these results is that melatonin injections at 17:00 hr depressed reproductive hormone levels and these depressed levels altered immune measures.     

Daily variation in the content of indoleamines, catecholamines and related compounds in the pineal gland of Syrian hamsters kept under long and short photoperiods

Abstract: This study examined the diurnal changes in the content of 5-hydroxytryptophan (5-HTP), serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), N-acetylserotonin (NAS), melatonin, 5-methoxytryptophol (5-ML), noradrenaline (NA), dopamine (DA), and 3,4-dihydroxyphenylacetic acid (DOPAC) in the pineal gland of Syrian hamsters kept under long (14L: 10D) and short (10L: 14D) photoperiods. The nocturnal increase in NAS and melatonin levels was dependent upon the prevailing photoperiod, with a prolonged duration when the night lengthened. In both photoperiods, NAS and melatonin contents increased several hours after the onset of darkness, and, in animals kept in short photoperiod, the levels of both compounds began to decrease before light onset. On the contrary, decreases were noted in 5-HT, 5-HIAA, and 5-ML contents during the night, which was directly proportional to the dark phase. 5-HTP levels did not show a rhythmic variation. Correlations between the mean values of 5-HT-related compounds showing daily rhythms were very high when group means were compared, but they decreased when values from individual animals were considered. In addition, when correlations were calculated on per-animal basis during the night phase, a weak negative correlation was found for 5-HT vs NAS and 5-HT vs melatonin, although the correlation of 5-HT with positively 5-HT-correlated compounds (5-HIAA and 5-ML) continued to be high. These results indicate that the nocturnal increase in the N-acetyl transferase activity is the major factor generating the rhythm of pineal 5-HT content, but that other photoperiod-dependent mechanisms (i.e., 5-HT synthesis or release) seem to be also implicated. On the other hand, this study shows that NA content in the Syrian hamster pineal gland does not exhibit daily variations, although marked nocturnal increases in the levels of DA and DOPAC were evident. These results suggest the existence of parallel daily alterations in pineal catecholamine synthesis and release, and suggest a role for DA in the pineal activation at night.     

Localization and quantification of high-affinity melatonin binding sites in Rana pipiens retina

Melatonin binding was localized to the inner plexiform layer (IPL) of the frog retina by in vitro autoradiography, using 2-125I-melatonin as the radioligand. Radioreceptor binding assays of frog retinal homogenate demonstrated saturable melatonin binding. Scatchard analysis revealed a single population of binding sites with an apparent dissociation constant (Kd) of 125 pM, with a Bmax of 0.138 fmoles/mg of protein. These results suggest that high-affinity melatonin binding sites are present in the IPL of the frog retina, which may reflect the presence of melatonin receptors in this synaptic layer.     

Relative Efficacy of Melatonin and 5-Methoxytryptamine in Terms of Their Antigonadotrophic and Counterantigonadotrophic Actions in Male Syrian Hamsters

Antigonadotrophic and counterantigonadotrophic activities of melatonin and 5-methoxytryptamine (5-MT) were quantitatively compared in male Syrian hamsters. In long day conditions, the daily afternoon administration of either 5, 15, 25, 50, 100 or 200 μg melatonin induced testicular regression within 10 wk; under the same circumstances, only the 200-μg dosage of 5-MT was able to suppress testicular weights. Thus, 5-MT appears to have about one-tenth the antigonadotrophic action of melatonin in the male Syrian hamster. In short days, the subcutaneous implantation of either 50 or 100 μg melatonin (every 2 wk in beeswax) prevented testicular regression whereas it required much larger doses of 5-MT (1 mg every 2 wk in beeswax) to achieve the same counterantigonadotrophic action. In terms of both their antigonadotrophic and counterantigonadotrophic effects, hamsters seem to be more sensitive to melatonin than to 5-MT.     

Characterization of melatonin high-affinity binding sites in purified cell nuclei of the hamster (Mesocricetus auratus) harderian gland

In the present paper, binding of melatonin to purified cell nuclei from harderian glands of male and female hamsters was assessed. Binding of 125I-melatonin to cell nuclei fulfills the criteria for binding to a receptor site. Binding kinetics exhibit properties such as dependence on time and temperature as well as reversibility, saturability, high affinity and specificity. The dissociation constants (K(D)) and the number of binding sites (B(max)) for the binding of 125I-melatonin to harderian gland nuclei were 260 +/- 56 pm and 12.2 +/- 0.8 fmol/mg protein in male glands, and 280 +/- 43 pm and 9.8 +/- 0.6 fmol/mg protein in female glands, respectively. Competition experiments showed IC50 values for melatonin of 250 +/- 45 pm and 290 +/- 68 pm in male and female glands, respectively. Other indoleamines such as N-acetylserotonine and 5-metoxytryptamine showed IC50 values in the micromolar range, suggesting that the binding sites are specific for melatonin. Hill analyses of the data show nH values of 0.96-0.98, suggesting the existence of a single class of binding sites. These data indicate that specific 125I-melatonin binding sites exist in the cell nuclei of Harderian glands in male as well as in female hamsters, without significant differences between them. The K(D) and B(max) values obtained from the binding in both sexes correlates well with the concentration of melatonin described in these respective Harderian glands. It is hypothesized that the nuclear binding sites of melatonin here described could be a physiological melatonin receptor, which may be involved in the genomic-dependent antioxidant effects of melatonin on hamster Harderian glands elsewhere reported.     

Retinal photoreceptors of Syrian hamsters undergo oxidative stress during streptozotocin-induced diabetes

Aims/hypothesis: The aim of this study was to verify whether retinal photoreceptors, like other tissues, are subject to oxidative stress during diabetes. Methods: Oxidative stress was monitored by the oxidation of preloaded dehydrorhodamine 123 into fluorescent rhodamine 123, during a period of intense illumination of isolated rod retinal receptor cells. These were obtained from 22 Syrian hamsters injected with streptozotocin (50 mg/kg body weight., intraperitoneal route) 90 days before the study began. Eleven hamsters were treated daily with melatonin (0.4 mg/kg body wt., per os), an antioxidant synthesized within photoreceptors. Isolated photoreceptors were bathed on the stage of a Leitz Orthoplan microscope, where the fluorescent lamp also served as the light stimulus (485 nm). Fluorescence irradiance was measured by photometry and stored in a personal computer for further analysis. Results: The light-induced oxidant production greatly decreased and was also delayed in the streptozotocin-injected hamsters compared with the control hamsters matched for age. Similar effects were obtained in control photoreceptors after 40 min incubation with 2–2'-azobis (2-amidinopropane) dihydrochloride, a potent lipoperoxidation inducer. The effect of melatonin was to partially restore the light-induced fluorescence response. Conclusion/interpretation: The depression of the light-induced oxidative response in diabetic photoreceptors could be ascribed to a hyperglycaemia-induced background of oxidative stress whereby the light-oxidizable substrate is actually lowered. Melatonin induces a larger fluorescence response during illumination, probably as a consequence of its antioxidant effect during diabetes, which would provide more oxidizable lipids. [Diabetologia (2002) 45: 121–124] Received: 23 September 2001 and in revised form: 27 September 2001