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Biomedical subjects

L Tamarkin

Publications and source records attributed to L Tamarkin.

At least 73 records · Page 4Linked to original sources
PubMed1981

The effects of environmental lighting on the daily melatonin rhythm in primate cerebrospinal fluid.

The effects of alterations in environmental lighting on the daily rhythm in cerebrospinal fluid concentrations of melatonin were studied in the rhesus monkey. It was found that acute exposure to darkness during the day did not markedly increase normally low daytime CSF melatonin levels, that light suppressed the normally high CSF melatonin values at night, and that 12-h phase shifts in the diurnal lighting cycle caused 12-h phase shifts in the rhythm. The daily rhythm persisted for 6.5 days of study in constant darkness and the phase of the rhythm was not affected in constant darkness by a 12-h phase shift in the daily delivery of food and daily care of the animals. These results support the notion that the melatonin rhythm in this primate species is endogenous in nature, and that light can act to both coordinate the rhythm to the 24-h day and to acutely suppress melatonin production.

Animals↗
PubMed1981

Melatonin inhibition and pinealectomy enhancement of 7,12-dimethylbenz(a)anthracene-induced mammary tumors in the rat.

The effects of the pineal hormone, melatonin, and of pinealectomy on the incidence of mammary adenocarcinoma in Sprague-Dawley rats treated with 7,12-dimethylbenz(alpha)-anthracene (DMBA) were investigated. Melatonin (2.5 mg/kg), begun on the same day as DMBA (5 mg) treatment and given daily in the afternoon for 90 days, significantly reduced the incidence of mammary tumors from 79% (control) to 20% (treated) (p less than 0.002). Rats pinealectomized at 20 days of age and treated with 7 mg of DMBA at 50 days of age had a higher incidence of tumors (88%) compared to control animals (22%). Fifteen mg of DMBA, which resulted in a higher incidence of tumors, reduced the difference between pinealectomized and control animals. Melatonin only partially reversed the effects of pinealectomy, reducing the incidence from 87% (pinealectomy alone) to 63% (pinealectomy plus melatonin); however, the tumor incidence was still lower (27%) in nonpinealectomized, melatonin-treated animals. Assessment of plasma prolactin, luteinizing hormone, follicle-stimulating hormone, estradiol, and cortisol in DMBA-treated tumor-free and tumor-bearing animals revealed a significantly lower plasma prolactin concentration [27 +/- 5 (S.E.) ng/ml] in melatonin-treated animals as compared to vehicle-treated animals [65 +/- 8 ng/ml]. The concentration of plasma prolactin was less in melatonin-treated, pinealectomized rats (55 +/- 10 ng/ml) as compared to vehicle-treated, pinealectomized animals (101 +/- 13 ng/ml). Other hormones were not affected by melatonin treatment. These data support the hypothesis that melatonin inhibits the development of DMBA-induced mammary tumors in the rat while removal of the pineal gland stimulates development of such tumors. Additionally, these experiments provide evidence that these effects may be mediated by a suppression of plasma prolactin levels.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1981

Effects of damage to the suprachiasmatic area of the anterior hypothalamus on the daily melatonin and cortisol rhythms in the rhesus monkey.

The effects of lesions of the suprachiasmatic nucleus (SCN) on the circadian rhythms in melatonin and cortisol were examined in the rhesus monkey. The concentrations of the two hormones were monitored in cerebrospinal fluid (CSF) withdrawn from two sham-operated animals, two animals with complete bilateral SCN lesions, and two animals with partial SCN damage at 4 and 8 months after surgery. In the sham-operated animals, as in the intact animal, the daily melatonin rhythm was entrained to the daily light-dark cycle, was suppressed in constant light, and persisted in constant darkness. In contrast, neither animal with complete SCN ablation exhibited a daily pattern of CSF melatonin in diurnal lighting at 4 months after surgery nor were their melatonin levels at constant low values. Furthermore, CSF melatonin concentrations were not suppressed in either animal by constant light. Surprisingly, at 8 months after surgery, spectral analysis revealed a 24-hr component to the melatonin patterns for each animal with complete SCN ablation in both diurnal lighting and constant darkness. The two animals with partial SCN damage exhibited a daily melatonin rhythm in diurnal lighting, but constant light did not suppress CSF melatonin concentrations consistently. Daily rhythms persisted in both for a 6 1/2-d period of study in constant darkness. In contrast to the alterations in the melatonin rhythm after SCN damage, there was no apparent effect of either partial or complete SCN ablation on the daily CSF cortisol rhythm. These data indicate that, in the rhesus monkey, the SCN is important for the generation, photic entrainment, and photic suppression of the melatonin rhythm. However, circadian oscillators located outside of the SCN region may control the normal daily cortisol rhythm and perhaps the melatonin rhythm in the absence of the SCN.

Amino Acids↗
PubMed1980

Ontogeny of the pineal melatonin rhythm in the Syrian (Mesocricetus auratus) and Siberian (Phodopus sungorus) hamsters and in the rat.

The ontogeny of the pineal melatonin rhythm was determined in three rodent species. Pineal glands were obtained either during the day or during the expected peak in melatonin at night. In all species the rhythm was first detected during the second week of life. Investigations of the photic regulation of pineal melatonin revealed that light could inhibit the nocturnal increase in melatonin in all species by the end of the second week of life. These studies indicate that for these species the development of the rhythm in pineal melatonin and the development of the mechanism involved in the photic suppression of the nocturnal increase in melatonin are independent of the role the pineal gland plays in regulating reproductive function in response to changes in environmental lighting.

Aging↗
PubMed1980

Studies on the daily pattern of pineal melatonin in the Syrian hamster.

In the Syrian hamster, a sharp peak in pineal melatonin occurs toward the end of the dark period. In the present communication, we describe characteristics of this rhythm. First, the time of the initial increase in pineal melatonin is not altered by daily melatonin injections that induce gonadal regression. Second, the rapid decrease of pineal melatonin in the morning is not prevented by acutely extending the dark period. Third, a consistent nocturnal increase in pineal melatonin is not observed in a 20-h light, 4-h darkness lighting schedule. However, acute exposure to a longer dark period, at the appropriate time of day, allows expression of the pineal melatonin rhythm in these animals. Finally, the rhythm in pineal melatonin appears to be truly circadian and is tightly coupled to the circadian rhythm in running activity.

Animals↗
PubMed1979

A diurnal melatonin rhythm in primate cerebrospinal fluid.

Melatonin was measured in cerebrospinal fluid (CSF) withdrawn continuously from partially restrained rhesys monkeys. There was a daily rhythm in CSF melatonin with peak night values 2- to greater than 15-fold higher than day values. The increase occurred shortly after lights were turned off, and the decrease occurred soon after lights were turned on. There was substantial variation in the magnitude of the rhythm among animals. However, there was little day to day variation in the rhythm of individual animals studied for 3 or 6 consecutive days. Although the concentration of melatonin in CSF was lower than that in plasma, the changes in CSF melatonin concentrations seemed to reflect large daily changes in plasma melatonin concentrations.

Animals↗
PubMed1977

Melatonin induction of gonadal quiescence in pinealectomized Syrian hamsters.

Pinealectomized Syrian hamsters were injected thrice daily with 25 micrograms of melatonin per injection. The injections were administered at 3-hour intervals either during the day or during the night of a photoperiodic cycle of 14 hours of light and 10 hours of darkness. After 6 weeks of treatment with melatonin during the night, both pinealectomized and intact hamsters had reduced testis weight, and pinealectomized hamsters showed decreased levels of serum gonadotropins. Injection of melatonin during the day for 7 weeks either once (75 micrograms) a day or thrice (25 micrograms per injection) daily caused a reduction in testis weight in pinealectomized hamsters. Both pinealectomized and intact females injected with melatonin thrice daily during the day became anovulatory by week 7 of treatment. These results are similar to those observed when hamsters are exposed to a short photoperiod, suggesting that melatonin may be acting as a hormone in mediating the effects of photoperiod on the reproductive system of the Syrian hamster.

Animals↗
PubMed1977

Effect of melatonin administered during the night on reproductive function in the Syrian hamster.

Syrian hamsters were maintained on a long photoperiod (lights on 0600-2000 h) and injected daily with melatonin (10 microgram per injection) for 6-7 weeks. Females injected at 2000 h or 0400 h ceased estrous cyclicity, and males treated similarly at these times had reduced testis weights by the sixth week of treatment. Daily administration of the same dosage of melatonin at 2400 and 0100 h failed to interrupt estrous cyclicity or reduce testis weight. These observations suggest that exogenous melatonin administered at 2000 h or 0400 h may be temporally adding to endogenous circulating melatonin, inducing gonadal quiescence.

Animals↗
PubMed1976

Regulation of serum gonadotropins by photoperiod and testicular hormone in the Syrian hamster.

Male hamsters were maintained on long (14L:10D) or short (10L:14D) photoperiods. The serum concentrations of LH and FSH were reduced in the animals kept on the short photoperiod, and these animals had atrophied testes and sex accessories. Serum gonadotropin concentrations increased following castration in both long and short photoperiods, but gonadotropin secretion was inhibited by much smaller doses of testosterone in the males maintained on the short photoperiod as compared to males kept on a long photoperiod. The levels of testosterone required to suppress serum gonadotropin levels in castrated animals corresponded reasonably well with the serum androgen levels observed in intact males, suggesting that serum androgen is a major regulator of gonadotropin secretion in the male hamster.

Androgens↗
PubMed1976

Effect of melatonin on the reproductive systems of male and female Syrian hamsters: a diurnal rhythm in sensitivity to melatonin.

Hamsters were maintained on a long photoperiod (14L:10D) and were injected once daily with melatonin (10-25 mug) or sesame oil. Males which received melatonin during the afternoon (e.g., 6.5-13.75 h after lights-on) showed regressed testes and decreased levels of serum LH and FSH after several weeks of treatment. Injections of the oil vehicle or injections of melatonin given in the morning (3 h after lights-on) had no detectable effect on testicular size or on serum gonadotropins. Females which received melatonin during the afternoon became acyclic after several weeks of treatment and showed a diurnal pattern of LH secretion. The acyclic females required 4-6 weeks to resume estrous cyclicity following termination of the melatonin injections. The effects of melatonin on gonadal function and on serum gonadotropin concentrations in both sexes were similar to the previously observed effects of prolonged exposure to short photoperiods. These results indicate that chronic daily injections of melatonin can depress reproductive function in hamsters and that the effectiveness of the injections is dependent upon the time of day at which they are administered.

Animals↗
PubMedDate not supplied

Effects of serotonergic agonists and antagonists on corticotropin-releasing hormone secretion by explanted rat hypothalami.

Experimental evidence suggests that serotonin (5HT) is excitatory to the hypothalamic-pituitary-adrenal axis and that this effect involves activation of both hypothalamic corticotropin-releasing hormone (CRH) and pituitary ACTH secretion. The present study was undertaken to examine the mechanism by which 5HT stimulates the central component of the HPA axis. To accomplish this we employed an in vitro rat hypothalamic organ culture system in which CRH secretion from single explanted hypothalami was measured by specific radioimmunoassay (IR-rCRH). All experiments were performed after an overnight (15-18 hr) preincubation. Serotonin stimulated IR-rCRH secretion in a dose-dependent fashion. The response was bell-shaped and the peak effect was observed at the concentration of 10(-9) M. The stimulatory effect of 10(-9) M 5HT was antagonized by the 5HT1 and 5HT2 receptor metergoline and by the selective 5HT2 receptor antagonists ketanserin and ritanserin. The muscarinic antagonist atropine, the nicotinic antagonist hexamethonium and the alpha-adrenergic receptor antagonist phentolamine, on the other hand, did not inhibit 5HT-induced IR-rCRH secretion. The specific 5HT2 receptor agonist 1-(2,5-dimethoxy-4-iodo-phenyl)-2-aminopropane (DOI) stimulated IR-rCRH secretion in a dose-dependent fashion. The response was bell-shaped with peak of effect reached at the concentration of 10(-9) M. We also tested the ability of the 5HT agonist meta-chlorophenylpiperazine (m-CPP) and of the selective 5HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) to cause CRH secretion. Although both m-CPP and 8-OH-DPAT stimulated IR-rCRH secretion in a dose-dependent fashion, several differences were observed when their effect was compared to that of 5HT. These included a different shape of the dose-response curve, a lower maximal stimulatory effect and a different maximal stimulatory concentration. These findings suggest that serotonin stimulates CRH secretion by explanted rat hypothalami and that this effect appears to be mediated mainly through a 5HT2 receptor mechanism.

Animals↗
PubMedDate not supplied

Melatonin increases oestrogen receptor binding activity of human breast cancer cells.

Breast cancer is frequently a hormone-dependent tumour, and several studies have suggested that the pineal gland hormone melatonin may influence the growth and development of this malignancy. Subcutaneous injections of melatonin have been shown to inhibit, and pinealectomy to enhance, the development of dimethyl benz(a)anthracene (DMBA)-induced mammary tumours in rats. Use of the psychotropic drug thorazine, which increases plasma melatonin levels, has been associated with a decreased incidence of breast cancer in psychiatric patients. Calcification of the pineal gland has been correlated with an increased incidence of breast cancer in women. While the mechanism by which melatonin influences these tumours is unknown, both human breast cancer and DMBA-induced tumours contain oestrogen receptors (ER) and respond to changes in the oestrogen milieu. We therefore wondered whether melatonin might be altering ER binding activity of these tumours. We report here that in vitro incubation of MCF-7 human breast cancer cells with melatonin in physiological conditions increased the cytoplasmic and nuclear ER activity of these cells within 40 min, giving no change in the equilibrium dissociation constant (Kd) of the receptor. This induction was blocked by cycloheximide, and thus requires continuous protein synthesis. The modulation of ER binding activity of breast cancer by another endogenous hormone may be important for understanding the behaviour and treatment of this disease, and may provide insight into the factors regulating the synthesis and metabolism of steroid hormone receptors.

Breast Neoplasms↗
PubMedDate not supplied

Learned immunosuppression is associated with an increased risk of chemically-induced tumors.

Based on the hypothesis that certain aspects of the CNS and immune system interact and that altered immune function affects carcinogenesis, an animal model was developed to examine the effects of learned immunosuppression on the development of a chemically induced tumor. In two experiments, we evaluated whether mice, for which immunosuppression was associated with a neutral (conditioned) stimulus, would exhibit an increased susceptibility to tumor development upon reexposure to the conditioned stimulus, as compared to nonconditioned and control animals. A taste aversion conditioning paradigm, based on classical conditioning techniques, was employed to suppress immune function using the cytotoxic and immunosuppressive drug cyclophosphamide (CY) as the unconditioned stimulus and consequently increase the risk of chemically induced tumorigenesis. CY (100 mg/kg, intraperitoneal) was paired with saccharin in the drinking water (0.1%) of adult female mice (CF-1). Conditioned mice were exposed to saccharin twice in the absence of CY, on days 4 and 7 after the first exposure (day 1). All mice were injected with the chemical carcinogen 9,10-dimethylbenzanthracene (DMBA, 50 mg/kg, subcutaneous) on day 4 of conditioning. Two subsequent exposures to saccharin alone substantially increased the risk of developing DMBA-induced tumors (ranging from 83-91%), as compared to control animals (36%) that had not received this pairing. Mice that received all agents (i.e., CY, DMBA, and saccharin) in a slightly different order did not display elevated tumor incidence. Three separate exposures to CY also significantly increased the number of animals developing tumors in response to the carcinogen (75%). Mice were observed for at least 8 weeks after conditioning.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗