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Melatonin, a hormone secreted by the pineal glands, has attracted the attention of numerous researchers due to its fascinating chemistry and biochemistry. An industrially feasible synthesis is described herein; a Japp-Klingemann reaction is used to form the indole skeleton.
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We are presently at a point in human pineal research where we have recognized through melatonin assay the presence of pineal dysfunction in a variety of disease categories. Melatonin may now be quickly and accurately quantified in a range of body fluids, and our well-developed knowledge of the basic biochemistry and neuroanatomical connections of the pineal enables us to see at least how abnormalities in melatonin secretion occur, if not why. The reported increases in melatonin secretion in early malignancy with a reduction in secretion during the neoplastic process is interesting, as is the great decline in the elevated melatonin level of oncological patients following institution of chemotherapy. The correlations between estrogen receptor status of breast cancer and melatonin level, and between neoplastic status of the prostate and melatonin secretion, points to interesting differential diagnostic utilities of melatonin analysis in these conditions. Furthermore, an etiological involvement of melatonin in neoplasia is suggested by experiments which have demonstrated the capacity of melatonin to induce mitotic arrest, and to increase the affinity of mammary carcinoma estrogen receptors for their substrate. These are important observations among many others of direct relevance to research and treatment in oncology, and warrant much further investigation. Melatonin assay may also prove useful in the prognostic monitoring of patients treated for melatonin-secreting pineal tumors, and in such cases may form a logical part of follow-up investigation in the screening for metastatic complication. In psychiatry research, melatonin analysis has functioned as a tool by which alterations in pineal function within specific psychiatric diagnoses have been demonstrated and assessed. Its uses in the assessment of the effects of antidepressant drugs on central beta-receptor function, as a tool in the investigation of light-induced alterations in pineal function in manic-depressive individuals, and as a tool in the investigation of the putative pineal-adrenocortical functional interaction have produced the fundamental building blocks of modern research into the pineal and psychiatry. The experimental clinical utility of melatonin assay is not localized to oncology and psychiatry, and significant alterations in melatonin secretion have been reported in several other disease categories. Indeed, the demonstration of markedly elevated melatonin secretion in patients with spina bifida occulta might suggest that assay of melatonin in amniotic fluid could be useful as an experimental adjunct in the prenatal diagnosis of this condition.(ABSTRACT TRUNCATED AT 400 WORDS)
Long-term implants releasing a small quantity of melatonin (45 nanograms per day) were used to determine the brain sites of the hormone's antigonadal action in a photoperiodic species, the white-footed mouse (Peromyscus leucopus). Implants in the medial preoptic and supra- and retrochiasmatic areas elicited completed gonadal regression after 7 weeks. Implants in other brain regions had little effect on the animals' reproductive state.