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Biomedical subjects

M D Rollag

Publications and source records attributed to M D Rollag.

At least 55 records · Page 3Linked to original sources

The effect of daily injections and constant release implants of melatonin on the endogenous pineal melatonin rhythm in golden hamsters.

In this study we tested the hypothesis that exogenous melatonin exerts its effects on the reproductive system of hamsters by directly or indirectly altering the endogenous rhythm of melatonin production and release. Melatonin was injected in male hamsters housed on LD 14:10 (lights 0600-2000 hr) either at 1200 or 1900 hr (15 micrograms in 0.1 ml ethanol:saline 1:10) daily for 12 weeks. Testicular regression occurred in all animals of the 1900-hr injection group, while melatonin injected at noon was without effect. A third group of animals received small implants of melatonin subcutaneously at 0, 4, and 8 weeks. Implants were 4 mm in length and contained a melatonin:beeswax mixture (1:25) drawn up into polyethylene tubing (2.2 mm i.d.). These implants release approximately 10-15 micrograms melatonin/day, and had no effect on testicular size, as these animals also remained on LD 14:10. After 12 weeks the animals of each group were sacrificed at 1- or 2-hr intervals around the clock. Pineals were saved and assayed for melatonin content. In each group the nocturnal rhythm of pineal melatonin was similar; peak melatonin levels were achieved 6 hr after lights out (0200 hr) and levels remained elevated for approximately 4 hr. These results exclude a mode of action of exogenous melatonin on the pineal melatonin rhythm as a basis for the testicular response to melatonin in hamsters. They also pose some interesting questions of feedback regulation by melatonin on its own production and release.

Animals↗

Ability of tryptophan derivatives to mimic melatonin's action upon the Syrian hamster reproductive system.

The ability of 18 different tryptophan derivatives to induce gonadal regression in Syrian hamsters when injected daily at either midday or late evening has been examined. The compounds chosen have either been identified within mammalian pineal glands or are thought to be possible metabolic derivatives of melatonin. Of the compounds tested, only melatonin and 5-methoxytryptamine were found to possess antigonadotropic activity. 5-Methoxy-tryptamine's potency, however, was 1/10th that of melatonin and, like melatonin, 5-methoxytryptamine was effective when injected in the evening but not when injected during midday. In addition to the general survey of tryptophan derivatives for antigonadal capability when injected, 5-methoxytryptamine, melatonin, and 5-methoxytryptophol were compared relative to their abilities to prevent photo-induced gonadal regression when administered within beeswax implants. Again 5-methoxytryptamine and melatonin, but not 5-methoxytryptophol, were effective with 5-methoxytryptamine's potency being less than that of melatonin. These results indirectly support the contention that melatonin is the pineal product which mediates photoperiodic effects upon the Syrian hamster reproductive system.

5-Methoxytryptamine↗

Ontogeny of the gonadal response of golden hamsters to short photoperiod, blinding, and melatonin.

The age dependency of the time delay preceding a gonadal response to short photoperiod, blinding, and daily evening melatonin injection in young male and female hamsters has been examined to determine why the reproductive system of prepubertal golden hamsters is apparently unaffected by short-day treatment. Anestrous occurred in 50% of the female hamsters during the 10th week after blinding whether or not blinding occurred at 3, 5, 7, or 9 weeks of age. A similar latency was found following initiation of melatonin injections although the variance was greater (50% became anestrous during the 8th, 11th, 9th, and 8th week after initiation at ages of 3, 5, 7, and 9 weeks, respectively). After transfer to short days, however, females were 18 to 22 weeks old before 50% had become anestrous and the latency intervals were 19, 13, 11, and 10 weeks for transfer at 3, 5, 7, and 9 weeks of age, respectively. In males, mean testicular weights decreased to 50% of control values during the 9th and 10th week following blinding regardless of the age at which blinding occurred; the latency following initiation of melatonin injection or transfer to short days ranged between 8 and 11 weeks. These data support the conclusion that prepubertal male and female golden hamsters 3 weeks of age and older respond to light deprivation and melatonin treatment in the same manner as adults, but that the latency of the response is such that sexual maturity is attained before regression occurs. The response of 3-week-old female hamsters to short photoperiods, however, is apparently confounded by factors not governed by the pineal gland.

Aging↗

Acute effects of unilateral or bilateral superior cervical ganglionectomy on rat pineal N-acetyltransferase activity and melatonin content.

Acute bilateral superior cervical ganglionectomy (SCGX) completely prevents the nocturnal rises in pineal N-acetyltransferase (NAT) activity and melatonin content in male rats kept in light-dark cycles of 14:10. Unilateral SCGX causes the NAT and melatonin levels to be intermediate between those in sham-operated control rats and those in rats from which both ganglia had been removed.

Acetyltransferases↗

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.

Animals↗

[Melatonin and LH secretion patterns in pubertal boys (author's transl)].

Plasma melatonin and LH were measured at 20 minute intervals for 24 hours in four normal pubertal boys. All four subjects showed a significant augmentation of LH and melatonin during noctural sleep. There was also a significant correlation between the LH and melatonin levels (p less than 0.001). There were periods of episodic secretion of melanin during the diurnal waking period which seemed related to "stress". These data indicate that the peripheral concentrations of melatonin which occur during sleep are insufficient to prevent spontaneous LH secretion during puberty.

Adolescent↗

Pineal serotonin N-acetyltransferase activity and melatonin concentrations in prepubertal and adult Syrian hamsters exposed to short daily photoperiods.

Pineal serotonin N-acetyltransferase activity (NAT) and melatonin concentrations were determined at various intervals in prepubertal (35 days old) and adult male hamsters (74 day old) throughout a 24 hour period with the animals kept in a light:dark cycle of 6:18 (lights on at 0600 h and off at 1200 h). In prepubertal animals, daytime pineal NAT activity of 0.20-0.28 nmoles 14C-N-acetyltryptamine/pineal/hour was maintained for 8 hours after the initiation of darkness. Peak pineal NAT activity of 0.46 +/- 0.64 nmoles 14C-N-acetyltryptamine/pineal/hour occurred 13 hours after the onset of darkness and remained significantly elevated until 0400 h (p less than 0.001). Daytime pineal melatonin concentrations of 78-194 pg/pineal gland also were maintained for 8 hours after the initiation of darkness. At 13 hours into the dark period, pineal melatonin concentrations rose to 788 +/- 150 pg/pineal gland (p less than 0.01 vs all other time points except 0230 h and 0400 h). At one hour before the onset of light both the pineal NAT activity and pineal melatonin concentrations returned to daytime values. Adult male hamsters had diurnal pineal NAT and melatonin rhythms which are indistinguishable from those found in the prepubertal animals.

Acclimatization↗

Melatonin: reproductive effects.

N-acetyl-5-methoxytryptamine, melatonin, is synthesized within and secreted from the pineal gland. Although the concentration of this constituent in the blood is diminished after surgical removal of the pineal gland it does not completely disappear. Other potential contributors to blood titers of melatonin include the retinas, the Harderian glands and the gastro-intestinal tract. Melatonin has a potent antigonadotrophic action in the Syrian hamster ( a highly photosensitive species) provided the indole is given during a restricted portion of the light phase of the light-dark cycle. This so-called sensitive period falls late in the light phase; melatonin acutely administered at other times has virtually no inhibitory influence on the reproductive physiology of hamsters. When melatonin is continuously available (from a subcutaneous deposit) it counteracts the antigonadotrophic influence of the pineal gland in light restricted or blinded hamsters, i.e., it causes a "functional pinealectomy". Furthermore, chronically available melatonin negates the antigonadotrophic capability of acute melatonin injections.

Animals↗