Stockgrand Ltd. Monitoring the biological clock. The biological clock.


Book: 'Melatonin and the Mamalian Pineal Gland' by J Arendt

Stockgrand staff and consultants have conducted research into melatonin and biological rhythms for the last 20-30 years, developing the first radioimmunoassays for melatonin (1975) and 6-sulphatoxymelatonin (1985) and pioneering the use of melatonin in circadian rhythm disorder (since 1982).

They continue to update technology and to pursue their research interests which range from molecular biology to the physiology of behaviour. Some publications resulting from Stockgrand reagents or expertise follow.

Stockgrand’s methodological references

Arendt, J., Bojkowski, C., Franey, C., Wright, J., & Marks, V. (1985). Immunoassay of 6-hydroxymelatonin sulfate in human plasma and urine: Abolition of the urinary 24-hour rhythm with atenolol. Journal of Clinical Endocrinology and Metabolism, 60, 1166-1173.

Skene, D.J., Smith, I. & Arendt, J. (1986). Radioimmunoassay of pineal 5-methoxytryptophol in different species: comparison with pineal melatonin content. J Endocrinology, 110, 177-184.

Bojkowski, C.J., Arendt, J., SHIH, M.C, & Markey, S.P. (1987). Melatonin secretion in humans assessed by measuring its metabolite, 6-sulphatoxymelatonin. Clinical Chemistry, 33, 1343-1348.

Bojkowski, C.J., Aldhous, M., English, J., Franey, C., Poulton, A.L., Skene, D. and Arendt, J. Suppression of nocturnal plasma melatonin and 6-sulphatoxymelatonin by bright and dim light in man. Horm.Met.Res. (1987) 19, 437-440.

Aldhous, M. & Arendt, J. (1988). Radioimmunoassay for 6-sulphatoxymelatonin in urine using an iodinated tracer. Annals Clinical Biochemistry, 25, 298-303.

Skene, D.J., Vivien-Roels, B. and Pévet, P. Day and nighttime concentrations of 5-methoxytryptophol and melatonin in the retina and pineal gland from different classes of vertebrates. Gen. Comp. Endocrinol. (1991) 84, 405-411.

English, J., Middleton, B.A., Arendt, J., & Wirz-Justice, A. (1993). Rapid direct measurement of melatonin in saliva using an iodinated tracer and solid phase second antibody. Annals Clinical Biochemistry, 30, 415-416.

Ross, J.K., Arendt, J., Horne, J., & Haston, W. (1995). Night-shift work in Antarctica: sleep characteristics and bright light treatment. Physiology and Behaviour, 57, 1169-1174.

Middleton, B., Arendt, J. and Stone, B. (1996) Human circadian rhythms in constant dim light (<8 lux) with knowledge of clock time. Journal of Sleep Research 1996;5:69-76.

Thapan K, Arendt J, Skene DJ. An action spectrum for melatonin suppression: evidence for a novel non-rod, non-cone photoreceptor system in humans. J Physiol 2001; 535:Pt 1 261-7


A selection of references from our laboratories (last 10 years)

Deacon, S. and Arendt, J. (1995) Melatonin-induced temperature suppression and its acute phase-shifting effects correlate in a dose-dependent manner in humans. Brain Res, 688, 77-85.

Ruberg, F.L., Skene, D.J., Hanifin, J.P., Rollag, M.D., English, J., Arendt, J. and Brainard, G.C. (1996) Melatonin regulation in humans with color vision deficiencies. J. Clin. Endocrinol. Metab. 81, 2980-2985.

Deacon, S. and Arendt, J (1996) Adapting to phase-shifts, II. Effects of melatonin and conflicting light treatment. Physiol Behav 59, 675-682.

Middleton, B., Stone, B. & Arendt, J. (1996) Melatonin and fragmented sleep patterns. Lancet, 348, 551-552.

Lockley, S.W., Skene, D.J., Tabandeh, H., Bird, A.C., Defrance, R., & Arendt, J. (1997). Relationship between napping and melatonin in the blind. Journal of Biological Rhythms, 12, 16-25.

Middleton, B., Arendt, J. & Stone, B. (1997) Complex effects of melatonin on human circadian rhythms in constant dim light. Journal of Biological Rhythms, 12, 467-475.

Lockley, S.W., Skene, D.J., Tabandeh, H., Bird, A.C., Defrance, R. and Arendt, J. (1997) Relationship between napping and melatonin in the blind. J. Biol. Rhythms 12, 16-25.

Lockley SW, Skene DJ, James K, Thapan K, Wright J, Arendt J. (2000) Melatonin administration can entrain the free-running circadian system of blind subjects. J Endocrinol 164, R1-6

Arendt J, Czeisler CA, Dawson D, Dijk DJ, Haimov I, Lavie P, Lewy AJ, Parkes JD, Skene DJ, Stone BM, Wirz-Justice A, Zhadnova I (2000) In what circumstances is melatonin a useful sleep therapy? Refereed Consensus Statement from a Symposium (Coordinator J Arendt) World Federation of Sleep Research Societies, Dresden, Germany, 5-9th October, 1999. J Sleep Res 9:397-398.

Lund J, Arendt J, Hampton SM, English J, Morgan LM. (2001) Postprandial hormone and metabolic responses amongst shift workers in Antarctica. J Endocrinol 171: 557-564

Middleton B, Stone B, Arendt J. (2002) Human circadian phase in 12:12 h, 200:<8 lux and 1000:<8 lux light-dark cycles, without scheduled sleep or activity. Neurosci Lett 329:1 41 .

Gibbs M, Hampton S, Morgan L, Arendt J. (2002) Adaptation of the circadian rhythm of 6-sulphatoxymelatonin to a shift schedule of seven nights followed by seven days in offshore oil installation workers. Neurosci Lett 325: 91-94

Ng L, Morgan L, Arendt J. (2003) Circadian adaptation in Antarctic shiftworkers: relationship to diurnal preference, season and subjective sleep. Chronobiol Int 1162-1164

Warman GR, Tripp H, Warman VL, Arendt J. 2003. Acute exposure to circularly polarized 50-Hz magnetic fields of 200-300 microT does not affect the pattern of melatonin secretion in young men. J Clin Endocrinol Metab. 88:5668-73.

Archer SN, Robilliard DL, Skene DJ, Smits M, Williams A, Arendt J, von Schantz M. (2003) A length polymorphism in the circadian clock gene Per 3 is linked to delayed sleep phase syndrome and extreme diurnal preference. Sleep 26:413-415.

Rajaratnam S M, Dijk D J, Middleton B, Stone B, Arendt J. (2003) Melatonin phase-shifts human circadian rhythms with no evidence of changes in the duration of endogenous melatonin secretion or the 24-hour production of reproductive hormones. J Clin Endocrinol Metab 88: 4303-9.

Warman, V. L., Dijk, D. J., Warman, G. R., Arendt, J. & Skene, D. J. (2003) Phase advancing human circadian rhythms with short wavelength light. Neurosci Letts 342, 37-40.

Rajaratnam SMW, Middleton B, Stone BM, Arendt J, Dijk D-J. (2004) Melatonin advances the circadian timing of EEG sleep and directly facilitates sleep without altering its duration in extended sleep opportunities. J Physiol 561:339-351.


Some recent reviews

Arendt J. (2000) Melatonin, circadian rhythms, and sleep. Editorial. N Engl J Med 343:15 1114-6

Rajaratnam SM, Arendt J. (2001) Health in a 24-h society. Lancet 358:9286 999-1005

Morgan L, Hampton S, Gibbs M, Arendt J. (2003) Circadian aspects of postprandial metabolism. (Review) Chronobiol Int 20:795-808.

Skene, D.J., Swaab, D.F. (2003) Melatonin rhythmicity: effect of age and Alzheimer’s disease. Exp. Gerontol. 38, 199-206.

Skene, D.J. (2003) Optimisation of light and melatonin to phase shift human circadian rhythms. J. Neuroendocrinol. 15, 438-441.

Mistlberger, R., Skene, D.J. (2004) Social influences on mammalian circadian rhythms: animal and human studies. Biological Reviews 79, 533-556.

Arendt J. The Pineal Gland: Basic Physiology and Clinical Implications. In: DeGroot LJ, Jameson JL. Endocrinology, 4th Edition, WB Saunders & Co., Philadelphia, 2001, pp 377-387. 5th Edition in press 2005.

Arendt J, Skene DJ. (2005) Melatonin as a chronobiotic. Sleep Medicine Reviews, 9: 25-39


Other laboratories using Stockgrand technology

Aeschbach,D., Sher,L., Postolache,T.T., Matthews,J.R., Jackson,M.A., & Wehr,T.A. (2003). A Longer Biological Night in Long Sleepers Than in Short Sleepers. J Clin Endocrinol Metab, 88, 26-30.

Arnulf I, Quintin P, Alvarez, JC, Vigil L, Touitou Y, Lebre AS, Bellenger A, Varoquaux O, Derenne JP, Allilaire JF, Benkelfat C, & Leboyer M (2002). Mid-morning Tryptophan Depletion Delays REM Sleep Onset in Healthy Subjects. Neuropsychopharmacology, 27, 843-851.

Crasson,M., Kjiri,S., Colin,A., Kjiri,K., L'Hermite-Baleriaux,M., Ansseau,M., & Legros,J.J. (2004). Serum melatonin and urinary 6-sulfatoxymelatonin in major depression. Psychoneuroendocrinology, 29, 1-12.

Debus,O.M., Lerchl,A., Bothe,H.W., Bremer,J., Fiedler,B., Franssen,M., Koehring,J., Steils,M., & Kurlemann,G. (2002). Spontaneous central melatonin secretion and resorption kinetics of exogenous melatonin: a ventricular CSF study. Journal of Pineal Research, 33, 213-217.

Frisk,U., Olsson,J., Nylen,P., & Hahn,R.G. (2004). Low melatonin excretion during mechanical ventilation in the intensive care unit. Clinical Science, 107, 47-53.

Grozinger,M., Hartter,S., Wang,X., Roschke,J., Hiemke,C., & Rose,D.M. (2000). Fluvoxamine Strongly Inhibits Melatonin Metabolism in a Patient With Low-Amplitude Melatonin Profile. Arch Gen Psychiatry, 57, 812-813.

Johnston, J. D., Cagampang, F. R. A., Stirland, J. A., Carr, A.-J. F., White, M. R. H., Davis, J. R. E., & Loudon, A. S. I (2003). Evidence for an endogenous per1- and ICER-independent seasonal timer in the hamster pituitary gland. FASEB J., 17, 810-815.

Kennaway, D.J. (1993). Urinary 6-sulphatoxymelatonin excretory rhythms in laboratory rats: effects of photoperiod and light. Brain Research, 603, 338-342.

Kennaway, D.J., Stamp, G.E., & Goble, F.C. (1992). Development of melatonin production in infants and the impact of prematurity. Journal of Clinical Endocrinology and Metabolism, 75, 367-369.

Lucas,R.J., Stirland,J.A., Darrow,J.M., Menaker,M., & Loudon,A.S.I. (1999). Free Running Circadian Rhythms of Melatonin, Luteinizing Hormone, and Cortisol in Syrian Hamsters Bearing the Circadian tau Mutation. Endocrinology, 140, 758-764.

Maywood, E.S., Hastings, M.H., Max, M., Ampleford, E., Menaker, M., & Loudon, A.S.I. (1993). Circadian and daily rhythms of melatonin in the blood and pineal gland of free-running and entrained Syrian hamsters. J Endocrinol, 136, 65-73.

Shanahan, T.L. & Czeisler, C.A. (1991). Light exposure induces equivalent phase shifts of the endogenous circadian rhythms of circulating plasma melatonin and core body temperature in men. Journal of Clinical Endocrinology and Metabolism, 73, 227-235.

Tordjman,S., Anderson,G.M., Pichard,N., Charbuy,H., & Touitou,Y. (2005). Nocturnal excretion of 6-sulphatoxymelatonin in children and adolescents with autistic disorder. Biological Psychiatry, 57, 134-138.

Travis,R.C., Allen,D.S., Fentiman,I.S., & Key,T.J. (2004). Melatonin and Breast Cancer: A Prospective Study. J Natl Cancer Inst, 96, 475-482.

Van Reeth, O., Sturis, J., Byrne, M.M., Blackman, J.D., L'Hermite-Baleriaux, M., Leproult, R., Oliner, C., Refetoff, S., Turek, F.W., & Van Cauter, E. (1994). Nocturnal exercise phase delays circadian rhythms of melatonin and thyrotropin secretion in normal men. Am J Physiol, 266, E964-E974.

Wehr, T. (1991). The durations of human melatonin secretion and sleep respond to changes in daylength (photoperiod). Journal of Clinical Endocrinology and Metabolism, 73, 1276-1280.

Wehr,T.A., Aeschbach,D., & Duncan,W.C.J. (2001). Evidence for a biological dawn and dusk in the human circadian timing system. J Physiol (Lond), 535, 937-951.


Some 'historical' references

Arendt, J., Symons, A.M., Laud, C.A. and Pryde, S.J. Melatonin can induce early onset of the breeding season in ewes.J. Endocr. (1983) 97, 395-400.

Arendt, J., Borbely, A.A., Franey, C. and Wright, The effects of chronic, small doses of melatonin given in the late afternoon on fatigue in man: a preliminary study. Neurosci. Letts. (1984) 45, 317-321.

Arendt, J., C. Bojkowski, S. Folkard, C. Franey, D. Minors, J. Waterhouse, R.A. Wever, C. Wildgruber, J. Wright and V. Marks. Some effects of melatonin and the control of its secretion in man. Ciba Foundation Symposium 117, Photoperiodism, melatonin and the pineal. (1985), 266-283. Ed. Evered, D. and Clark, S. Pitman, London.

Arendt, J., Aldhous, M. and Marks, V. Alleviation of jet-lag by melatonin: preliminary results of controlled double-blind trial. Brit.Med.J. (1986) 292, 1170.

Arendt, J. and Broadway, J. Phase response of human melatonin rhythms to bright light in Antarctica. J. Physiol. 377 (1986) 68P.

Wright, J., Aldhous, M., Franey, C., English, J. and Arendt, J. The effects of exogenous melatonin on endocrine function in man. Clin. Endocr. (1986)24, 375-382.

Skene, D.J., Pévet, P, Vivien-Roels, B., Masson-Pévet, M. and Arendt, J. Effect of different photoperiods on concentrations of 5-methoxytryptophol and melatonin in the pineal gland of the Syrian hamster. J. Endocr. (1987) 114, 301-309.

Arendt, J., Aldhous, M., Marks, M., Folkard, S., English, J., Marks, V. and Arendt, J. Some effects of jet-lag and their treatment by melatonin. Ergonomics, (1987) 30, 1379-1393.

Arendt, J. Aldhous, M.and Wright, J. Synchronisation of a disturbed sleep-wake cycle in a blind man by melatonin treatment. The Lancet (1988) i, 772-773.

Skene, D.J., Vivien-Roels, B., Sparks, D.L., Hunsaker, J.C., Pévet, P., Ravid, D. and Swaab, D.F. Daily variation in the concentration of melatonin and 5-methoxytryptophol in the human pineal gland: Effect of age and Alzheimer's disease. Brain Res. (1990) 528, 170-174.

Dahlitz,M.,Alvarez,B.,Vignau,J.,English,J., Arendt,J. and Parkes,J.D. Delayed sleep phase syndrome response to melatonin. Lancet i,(1991),337,1121-1124.

Folkard,S.,Arendt,J. and Clarke,M. Can melatonin improve shiftworkers tolerance of the night shift? Some preliminary findings . Chronobiology International, 10, 315-320 (1993).

Deacon, S. & Arendt, J. (1994). Phase-shifts in melatonin, 6-sulphatoxymelatonin and alertness rhythms after treatment with moderately bright light at night. Clinical Endocrinology, 40, 413-420.

Skene, D.J., Bojkowski, C.J. and Arendt, J. Comparison of the effects of acute fluvoxamine and desipramine administration on melatonin and cortisol production in humans. Br. J. Clin. Pharmacol. (1994) 37, 181-186.