Thomas H. Champney

Photoreceptor Damage and Eye Pigmentation: Influence on the Sensitivity of Rat Pineal N-Acetyltransferase Activity and Melatonin Levels to Light at Night

The threshold of light irradiance capable of inhibiting nighttime pineal serotonin N-acetyltransferase (NAT) activity and melatonin content, and the importance of intact photoreceptors and eye pigmentation on these changes, were investigated in the rat. Groups of intact albino and black-eyed rats and albino animals with light-induced photoreceptor damage were studied in the dark period before, and after 15 and 30 min of exposure to either 0.0005, 0.175 or 3.33 microW/cm2 irradiance of light. In animals with photoreceptor damage, the sensitivity of the pineal gland to light decreased so that only the highest irradiance tested (3.33 microW/cm2) was capable of totally inhibiting pineal NAT activity and melatonin levels. In one study, pineal NAT and melatonin levels in intact albino rats were inhibited by all three irradiances studied. In a second experiment, albino and black-eyed animals behaved identically, only responding with a depression in pineal NAT and melatonin after exposure to light irradiances of either 0.175 or 3.33 microW/cm2. In conclusion, the lowest irradiance of cool white light capable of inhibiting pineal NAT and melatonin in albino rats is around 0.0005 microW/cm2. At the irradiances studied, photoreceptor damage influences the response of pineal NAT and melatonin to acute light exposure at night. On the other hand, eye pigmentation does not seem to have a major effect on the nighttime inhibition of the pineal by light.

Alterations in components of the pineal melatonin synthetic pathway by acute insulin stress in the rat and Syrian hamster

Acute insulin stress increased plasma catecholamine levels in both the Syrian hamster and albino rat within 3 h after an intraperitoneal injection of either 5 or 10 units of insulin. In the rat, this stress caused a concurrent increase in pineal serotonin N-acetyltransferase (NAT) activity and melatonin content with no observable change in hydroxyindole-O-methyltransferase (HIOMT) activity. In the hamster, on the other hand, acute insulin stress did not alter pineal NAT activity, but depressed both HIOMT activity and melatonin content up to 3 h after the stress. These results present further evidence that catecholamines do not control hamster pineal melatonin synthesis by the same mechanism as observed in the rat.

Experimentally-induced diabetes reduces nocturnal pineal melatonin content in the Syrian hamster

Male, Syrian hamsters were rendered diabetic by either alloxan (60 mg/kg, i.v.) or streptozotocin (65 mg/kg, i.p.). Diabetic animals had reduced pineal melatonin contents during the night. Basal daytime values were not significantly altered. Diabetes may decrease melatonin synthesis by reducing the availability of glucose for metabolism or by decreasing the transport of tryptophan into pinealocytes for the synthesis of melatonin.

Hormonal modulation of pineal melatonin synthesis in rats and Syrian hamsters: effects of streptozotocin-induced diabetes and insulin injections.

Pineal levels of tryptophan, 5-hydroxytryptophan, serotonin, N-acetylserotonin, melatonin, 5-hydroxyindoleacetic acid and the enzyme activities of N-acetyltransferase and hydroxyindole-O-methyltransferase were determined in male albino rats and Syrian hamsters that were injected with insulin twice daily for three days, or injected with streptozotocin to induce diabetes. Neither insulin injections nor streptozotocin diabetes had any effect on pineal melatonin production in rats. In hamsters, diabetes reduced the nocturnal peak of pineal melatonin content by approximately one half, while insulin injections had no effect on pineal melatonin levels; however, insulin injections did cause a slight increase in pineal N-acetyltransferase activity. These findings indicate that the pineal gland of the hamster may be more sensitive to alterations in plasma insulin levels than the same organ in rats.

Comparison of the Effects of β‐Adrenergic Agents on Pineal Serotonin N‐Acetyltransferase Activity and Melatonin Content in Two Species of Hamsters

The nighttime rise in pineal melatonin levels can be blocked by administration of the β‐adrenergic receptor antagonist, propranolol, in both Syrian hamsters and rats. Although the administration of β‐adrenergic receptor agonists such as norepinephrine or isoproterenol stimulates pineal melatonin production in the rat, these drugs are without apparent effect on indole production in the Syrian hamster. To determine whether this lack of stimulatory effect in the Syrian hamster is characteristic of this species, a comparison of the effects of norepinephrine and isoproterenol on pineal serotonin N‐acetyltransferase activity and melatonin content was conducted. In contrast to their lack of effect in the Syrian hamster, norepinephrine and isoproterenol stimulated pineal serotonin N‐acetyltransferase activity and melatonin content in the Djungarian hamster. Hourly injection of norepinephrine during a continuation of light into the normal dark period stimulated increases in the activity of serotonin N‐acetyltransferase and melatonin content in the Djungarian hamster but was without effect on these pineal parameters in the Syrian hamster.

Pharmacological studies on the regulation of N-acetyltransferase activity and melatonin content of the pineal gland of the Syrian hamster

Thus far, all attempts to stimulate melatonin synthesis by β‐adrenergic receptor agonists in the Syrian hamster pineal gland have failed. Neither a wide range of dosages of isoproterenol (0.5 mg/kg to 24 mg/kg), nor prolonged treatment with norepinephrine, the natural neurotransmitter, increased N‐acetyltransferase (NAT) activity or melatonin production. In the present study, the administration of isoproterenol at night was likewise ineffective in advancing or enhancing the normal nightly melatonin peak. Also, we did not find a delayed effect 7 or 8 h after the administration of the drug. Furthermore, we tested the idea of coneurotransmitters such as octopamine or dopamine being possibly necessary for stimulation, but could not find any effect of these substances on melatonin synthesis. In addition, a parasympatholytic agent, atropine, did not increase the responsiveness to sympathomimetic agents. Administration of a phosphodiesterase inhibitor was also ineffective in stimulating NAT activity. On the other hand, isoproterenol did retard the drop in NAT and melatonin after lights‐on at night, indicating that β‐receptors are involved in maintaining elevated melatonin levels.

Effects of Injections and/or Chronic Implants of Melatonin and 5-Methoxytryptamine on Plasma Thyroid Hormones in Male and Female Syrian Hamsters

Plasma thyroid hormone concentrations in male and female Syrian hamsters were evaluated in five experiments after two pineal indoles, melatonin (MEL) and 5-methoxytryptamine (5-MT), were administered as chronic s.c. implants and/or daily afternoon injections. Circulating concentrations of thyroxine (T4), ordinarily maintained by the long photoperiod (LD 14:10), were inhibited by daily afternoon injections of 25 micrograms MEL but not 5-MT in male (experiment 1) and female (experiment 2) Syrian hamsters. The suppressive effect of MEL injections on T4 concentration in the long photoperiod was prevented in both sexes by a s.c. beeswax pellet containing either 1 mg MEL or 5-MT. In the third experiment, various doses of MEL or 5-MT were injected each afternoon for 12 weeks to compare the effectiveness of these two indoles in reducing T4 concentrations in hamsters maintained in the long photoperiod. Only the highest dose (200 micrograms) of 5-MT effectively suppressed T4 concentrations whereas all doses of MEL (greater than or equal to 5 micrograms) significantly reduced plasma T4. MEL or 5-MT (1-1,000 micrograms) were implanted in beeswax pellets in male hamsters exposed to short photoperiod (LD 10:14) to determine if either indole could prevent the short photoperiod-induced suppression of T4 (experiments 4 and 5). Regression and covariance analyses showed a significant log dose-related elevation of T4 in these hamsters, indicating equal potency of MEL and 5-MT in preventing the short photoperiod-induced suppression of T4. 5-MT given by either injection or implantation raised plasma triiodothyronine (T3) in female (experiment 2) but not in male hamsters.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in serotonin levels, N-acetyltransferase activity, hydroxyindole-O-methyltransferase activity, and melatonin levels in the pineal gland of the Richardson's ground squirrel in relation to the light-dark cycle

Pineal serotonin and melatonin levels and the activities of hydroxyindole-O-methyltransferase (HIOMT) and N-acetyltransferase (NAT) were studied over a 24-hour period in the pineal gland of the diurnally active Richardsons ground squirrel (Spermophilus richardsonii). Under alternating light-dark conditions (light:dark hours 14:10), pineal serotonin and melatonin levels exhibited a rhythm with high values occurring either during the day (serotonin) or during the night (melatonin). NAT activity was also markedly increased during darkness. HIOMT activity exhibited no 24-hour variation. Exposure of squirrels to constant light for 7 days exaggerated the serotonin rhythm, but obliterated the cycles of NAT and melatonin. Under constant darkness (for 7 days), the rhythms in serotonin, melatonin and NAT persisted, each having a period of about 24 h. In the second study, ground squirrels were exposed to light-dark cycles of either 8:16, 10:14 or 14:10. Under each of these photoperiodic environments, rhythms in pineal NAT and melatonin were apparent. Increasing the daily dark period from 10 to 14 h caused a prolongation of the elevated NAT and melatonin levels. However, a further prolongation of the daily dark period (to 16 h) did not further increase the duration of the rise in NAT and melatonin. The results show that continual light exposure (irradiance of 200 microW/cm2) for 7 days suppresses the pineal rhythms in both NAT activity and melatonin level in the Richardsons ground squirrel. Conversely, light exposure, rather than depressing the serotonin rhythm, actually exaggerates it. Constant darkness for 7 days has little influence on the 24-hour rhythms of either NAT or melatonin.(ABSTRACT TRUNCATED AT 250 WORDS)

Modification of testicular and thyroid function by chronic exposure to short photoperiod: a comparison in four rodent species

Exposure of male Syrian hamsters (Mesocricetus auratus) for 10 weeks to short photoperiod (SP) providing 10 hr light: 14 hr darkness (10:14 LD) produced a significant reduction in the weights of the reproductive organs, plasma thyroxine (T4) levels and free T4 index (FT4I) compared to the values of animals exposed to long photoperiod (LP, 14:10 LD). C57bl male house mice (Mus musculus) kept in SP (10:14 LD) had reproductive organ weights equivalent to those of mice kept in long days (14:10 LD) and lower T3 uptake (T3U) values. Male gerbils (Meriones unguiculatus) exposed to 13 weeks of SP (10:14 LD) had lower body weights, testes and seminal vesicle weights and higher T3U values compared to LP (14:10 LD) controls. However, no effect was seen on plasma T4 and triiodothyronine (T3) values nor the FT4I and free T3 index (FT3I). White-footed male mice (Peromyscus leucopus) exposed to SP (8:16 LD) had significantly lower testes and seminal vesicle weights while plasma T4 and T3 levels were unaffected. Snell strain house mice (Mus musculus) exposed to SP (8:16 LD) had normal reproductive organ weights compared to the values of LP-exposed (16:8 LD) control animals. However, there was a significant depression in T3 and in the FT3I in the SP animals.

Hormonal modulation of pineal melatonin synthesis in rats and syrian hamsters: Effects of adrenalectomy and corticosteroid implants

Pineal levels of tryptophan, 5-hydroxytryptophan, serotonin, N-acetylserotonin, melatonin, 5-hydroxyindoleacetic acid and the activities of the enzymes N-acetyltransferase and hydroxyindole-O-methyltransferase were determined in male albino rats and Syrian hamsters that were implanted with the appropriate corticosteroid or adrenalectomized two weeks earlier. Melatonin content and NAT activity were increased at 4 hours (during darkness) in adrenalectomized hamsters; conversely, no alterations in melatonin levels were observed in either adrenalectomized or implanted rats. It is suggested that the changes in adrenal function probably have a minor influence on pineal melatonin production.