Pineal Melatonin: transducer of biological time

1
Pineal Melatonin transducer of biological time

• Bhaskar N Joshi
• Department of Zoology
• Gulbarga University Gulbarga 585106 India
• bjo.shi_at_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
• SADs
• 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 Kleins 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
Thank You

• Melatonin