1. Pineal Melatonin: transducer of biological time Bhaskar N Joshi Department of Zoology Gulbarga University Gulbarga – 585106 India bjo.shi@sancharnet.in

2. Historical background • Discovered some 2300 years ago by Hirophilus, an Alexandrian anatomist • Considered as Seat of soul by Rene Descartes in 17th century 1596-1650

3. Sahasrar Chakra

4. Important Milestones in the history of pineal research • Observation by Heubner and Ogle that precocious sexual maturity was associated with pineal destruction by tumor. • Discovery of melatonin by Lerner et al 1958. • Melatonin is produced rhythmically and its production regulated by light. • Melatonin regulates reproduction.

5. Seasonal Reproduction

6. Physiological Functions • The rhythmic production melatonin is extensively used as a marker of the phase of the internal clock. • Melatonin is becoming increasingly respectable as a therapy for certain abnormalities of the circadian system. • In lower vertebrates the pineal is an important determinant of rhythms.

7. Physiological functions • In mammals whose seasonal functions are timed by daylength, melatonin production at night provides a universal time cue for changing daylength. • In humans, the evidence to date indicates that it serves to reinforce physiological events associated with darkness, such as sleep.

8. Physiological functions • Effects on reproduction, physiological rhythms and immune system • Anti-aging hormone • Tumor growth • Endocrine function • Many other miscellaneous functions

9. Though melatonin is being as therapeutic agent in the treatment of sleep disorders and jet-lagPhysiological functions in humans remain a matter for debate. • Melatonin

10. Pineal Structure • Human pineal gland is a small (100-150mg in humans), unpaired central structure, essentially an appendage of the brain • The 'penis of the brain • The mammalian pineal gland is secretory • In fish, amphibians and reptiles directly photoreceptive (the 'third eye') • In birds it has mixed photoreceptor and secretory function

11. Hypothetical Protovertebrate Vigh an Vigh-Teichmann, 1999

12. Lamprey Wurtman 1968

13. Teleost Fish Wurtman 1968

14. Frog Wurtman 1968

15. Lizard Wurtman 1968

16. Albino Rat Wurtman 1968

17. Human Pineal Gland

18. Epiphysis Cerebri in situ

19. Pineal Photoreceptor of Adult Frog

20. Cell Types in the Pineal Gland of Diverse Vertebrates A – Pinealocyte of fish & amphibians B – Pinealocytes of reptiles & birds C – Mammalian pinealocytes

21. Circadian clock regulation of melatonin biosynthesis

22. Diagrammatic representation of the control of production and the functions of melatonin, with regard to seasonal and circadian timing mechanisms . Josephine Arendt 2002

23. PHYSIOLOGICAL FUNCTIONS OF MELATONIN IN MAMMALS • When seasonal functions such as reproduction, pelage (coat growth and color), appetite, bodyweight are primarily timed by daylength, species are referred to as photoperiodic. • Long-duration melatonin is equivalent to short days and short-duration melatonin is equivalent to long days.

24. PHYSIOLOGICAL FUNCTIONS OF MELATONIN IN MAMMALS • Reproduction in domestic ruminants and the winter coat of animals such as mink, arctic foxes, and cashmere goats. • Manipulated by photoperiod and melatonin administration. • Commercial preparations of melatonin have been developed to this end.

25. PHYSIOLOGICAL FUNCTIONS OF MELATONIN IN MAMMALS • Timing of puberty. • Perception of photoperiod by fetus. • Melatonin injections to the mother can dictate the timing of postnatal reproductive development. • In vitro melatonin inhibits gonadotropin-releasing hormone (GnRH)-induced luteinizing hormone (LH) release by cultured rat pituitary glands from prepubertal animals.

26. Role of the Pineal Gland and Melatonin in Circadian Rhythms • Signal for circadian organization • Pinealectomy of rodents in constant light leads to disruption of the circadian system • SAD’s • Sleep-wake cycles

27. Average concentrations of melatonin in plasma (green) saliva (blue) and 6-sulphatoxymelatonin (aMT6s) in urine (red). Measurements by radioimmunoassay. (From: Josephine Arendt)

28. Hypothetical Protovertebrate 

29. The Eyes • “to suppose that the eye with all its inimitable contrivances . . . . .could have been formed by natural selection, seems, I confess, absurd in the highest degree” - Darwin 1860 Casting a Genetic Light on the Evolution of Eyes – Russell Fernald Science Vol 313, 2006

30. Light on Ancient photoreceptors • Two types of photoreceptors in early multi cellular organisms • Rhabdomeric – protostomes (worms, molluscs and arthropods • Cliliary – deuterostomes (vertebrates and their kin)

31. Rhabdomeric cells use microvilli whereas the ciliary ones use cilia for photoreception • Gene expression studies in Platynereis (Apical cells) • Lacally – Nature Nov 2004

32. Did pineal gland evolve to improve vision? • David Klein’s theory: • Retinaldehy + rhdopsin + light – generate electrical signal • Retialdehyde +arylalkylamines – toxic to eye • Evolution of AANAT to convert serotonin to menlatonin • Melatonin became a signal for darkness.

33. ThankYou • Melatonin