{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T16:07:27Z","timestamp":1791130047469,"version":"4.1.0"},"reference-count":65,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2001,8,1]],"date-time":"2001-08-01T00:00:00Z","timestamp":996624000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Biol Rhythms"],"published-print":{"date-parts":[[2001,8]]},"abstract":"<jats:p>Melatonin synthesis in the mammalian pineal gland is one of the best investigated output pathways of the circadian clock because it can be readily measured and is tightly regulated by a clearly defined input, the neurotransmitter norepinephrine. In this system, a regulatory scenario was deciphered that is centered around the cyclic AMP pathway but shows peculiar species-specific differences. In rodents, the cyclic AMP\u2013mediated, temporally sequential up-regulation of two transcription factors, the activator CREB (cyclic AMP\u2013responsive elementbinding protein) and the inhibitor ICER (inducible cyclic AMP\u2013dependent early repressor), is the core mechanism to determine rhythmic accumulation of the mRNA encoding for the rate-limiting enzyme in melatonin synthesis, the arylalkylamine N-acetyltransferase (AA-NAT). Thus, in rodents, the regulation of melatonin synthesis bears an essential transcriptional component, which, however, is flanked by posttranscriptional mechanisms. In contrast, in ungulates, and possibly also in primates, AA-NAT appears to be regulated exclusively on the posttranscriptional level. Here, increasing cyclic AMP levels inhibit the breakdown of constitutively synthesized AA-NAT protein by proteasomal proteolysis, leading to an elevated enzyme activity. Thus, self-restriction of cellular responses, as a reaction to external cues, is accomplished by different mechanisms in pinealocytes of different mammalian species. In such a temporally gated cellular adaptation, transcriptionally active products of clock genes may play a supplementary role. Their recent detection in the endogenously oscillating nonmammalian pineal organ and, notably, also in the slave oscillator of the mammalian pineal gland underlines that the mammalian pineal gland will continue to serve as an excellent model system to understand mechanisms of biological timing.<\/jats:p>","DOI":"10.1177\/074873001129002033","type":"journal-article","created":{"date-parts":[[2004,5,27]],"date-time":"2004-05-27T09:25:01Z","timestamp":1085649901000},"page":"312-325","source":"Crossref","is-referenced-by-count":75,"title":["Of Rodents and Ungulates and Melatonin: Creating a Uniform Code for Darkness by Different Signaling Mechanisms"],"prefix":"10.1177","volume":"16","author":[{"given":"J\u00f6rg H.","family":"Stehle","sequence":"first","affiliation":[{"name":"Dr. Senckenbergische Anatomie, Anatomisches Institut II, Hs 27, J. W. Goethe-Universit\u00e4t, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"von Gall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christof","family":"Schomerus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Horst-Werner","family":"Korf","sequence":"additional","affiliation":[{"name":"Dr. Senckenbergische Anatomie, Anatomisches Institut II, Johann Wolfgang Goethe-Universit\u00e4t Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2001,8,1]]},"reference":[{"key":"atypb1","volume-title":"Melatonin and the Mammalian Pineal Gland","author":"Arendt J","year":"1995"},{"key":"atypb2","doi-asserted-by":"publisher","DOI":"10.1126\/science.289.5488.2344"},{"key":"atypb3","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81816-4"},{"key":"atypb4","doi-asserted-by":"publisher","DOI":"10.1038\/378783a0"},{"key":"atypb5","doi-asserted-by":"publisher","DOI":"10.1016\/0079-6107(89)90002-3"},{"key":"atypb6","first-page":"32991","volume":"275","author":"Chong NW","year":"2000","journal-title":"J Biol Chem 2000"},{"key":"atypb7","doi-asserted-by":"publisher","DOI":"10.1038\/365855a0"},{"key":"atypb8","doi-asserted-by":"publisher","DOI":"10.1126\/science.270.5242.1681"},{"key":"atypb9","doi-asserted-by":"publisher","DOI":"10.1177\/074873001129002079"},{"key":"atypb10","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(95)12245-1"},{"key":"atypb11","doi-asserted-by":"publisher","DOI":"10.1042\/bj3280037"},{"key":"atypb12","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.24.14140"},{"key":"atypb13","doi-asserted-by":"publisher","DOI":"10.1038\/381083a0"},{"key":"atypb14","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(00)01129-0"},{"key":"atypb15","doi-asserted-by":"publisher","DOI":"10.1126\/science.279.5355.1358"},{"key":"atypb16","doi-asserted-by":"publisher","DOI":"10.1177\/074873001129002042"},{"key":"atypb17","doi-asserted-by":"publisher","DOI":"10.1126\/science.841305"},{"key":"atypb18","doi-asserted-by":"publisher","DOI":"10.1177\/074873049701200609"},{"key":"atypb19","doi-asserted-by":"publisher","DOI":"10.1002\/9780470720981.ch4"},{"key":"atypb20","first-page":"307","volume":"52","author":"Klein DC","year":"1997","journal-title":"Recent Prog Horm Res"},{"key":"atypb21","doi-asserted-by":"publisher","DOI":"10.1126\/science.177.4048.532"},{"key":"atypb22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-3-642-58932-4_1","volume":"146","author":"Korf HW","year":"1998","journal-title":"Adv Anat Embryol Cell Biol"},{"key":"atypb23","doi-asserted-by":"publisher","DOI":"10.1177\/074873001129002051"},{"key":"atypb24","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.19-09-03326.1999"},{"key":"atypb25","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-079X.1999.tb00613.x"},{"key":"atypb26","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.17.9938"},{"key":"atypb27","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90532-U"},{"key":"atypb28","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2826.2000.00459.x"},{"key":"atypb29","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1985.tb04069.x"},{"key":"atypb30","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(99)00324-9"},{"key":"atypb31","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.1998.00309.x"},{"key":"atypb32","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-079X.2000.290104.x"},{"key":"atypb33","doi-asserted-by":"publisher","DOI":"10.1124\/mol.56.2.279"},{"key":"atypb34","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(98)00356-5"},{"key":"atypb35","doi-asserted-by":"publisher","DOI":"10.1210\/endo-104-2-295"},{"key":"atypb36","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.19.8734"},{"key":"atypb37","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(94)90055-8"},{"key":"atypb38","doi-asserted-by":"publisher","DOI":"10.1210\/endo.137.7.8770929"},{"key":"atypb39","first-page":"439","volume":"47","author":"Roseboom PH","year":"1995","journal-title":"Mol Pharmacol"},{"key":"atypb40","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2000.0752123.x"},{"key":"atypb41","doi-asserted-by":"publisher","DOI":"10.1016\/0197-0186(95)00029-8"},{"key":"atypb42","doi-asserted-by":"publisher","DOI":"10.1007\/s004410050700"},{"key":"atypb43","doi-asserted-by":"publisher","DOI":"10.1177\/074873001129002024"},{"key":"atypb44","doi-asserted-by":"publisher","DOI":"10.1126\/science.288.5468.1013"},{"key":"atypb45","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80494-8"},{"key":"atypb46","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-079X.1995.tb00158.x"},{"key":"atypb47","first-page":"706","volume":"9","author":"Stehle JH","year":"1995","journal-title":"Mol Endocrinol"},{"key":"atypb48","doi-asserted-by":"publisher","DOI":"10.1038\/365314a0"},{"key":"atypb49","author":"Stehle JH","journal-title":"Eur J Neurosci"},{"key":"atypb50","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80366-9"},{"key":"atypb51","doi-asserted-by":"publisher","DOI":"10.1046\/j.0953-816X.2000.01324.x"},{"key":"atypb52","doi-asserted-by":"publisher","DOI":"10.1007\/BF00319113"},{"key":"atypb53","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.210248297"},{"key":"atypb54","doi-asserted-by":"publisher","DOI":"10.1126\/science.272.5260.419"},{"key":"atypb55","doi-asserted-by":"publisher","DOI":"10.1210\/endo-116-6-2167"},{"key":"atypb56","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.18-24-10389.1998"},{"key":"atypb57","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.2000.00990.x"},{"key":"atypb58","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2826.2001.00643.x"},{"key":"atypb59","first-page":"197","volume-title":"Regulation of Sleep and Circadian Rhythms","author":"Weaver DR","year":"1999"},{"key":"atypb60","doi-asserted-by":"publisher","DOI":"10.1177\/074873001129002060"},{"key":"atypb61","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(99)01724-X"},{"key":"atypb62","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(00)00602-3"},{"key":"atypb63","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-328X(00)00091-7"},{"key":"atypb64","doi-asserted-by":"publisher","DOI":"10.1038\/22659"},{"key":"atypb65","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80492-4"}],"container-title":["Journal of Biological Rhythms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/074873001129002033","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/074873001129002033","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T19:59:32Z","timestamp":1777492772000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/074873001129002033"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,8]]},"references-count":65,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2001,8]]}},"alternative-id":["10.1177\/074873001129002033"],"URL":"https:\/\/doi.org\/10.1177\/074873001129002033","relation":{},"ISSN":["0748-7304","1552-4531"],"issn-type":[{"value":"0748-7304","type":"print"},{"value":"1552-4531","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,8]]}}}