Photoperiod

1
Photoperiod reproduction
2
Overview

• Seasonal changes in physiology
• The Photo-neuroendocrine System
• Melatonin biosynthesis
• Regulation by photoperiod
• Melatonin target tissues
• Hypothalamus, pituitary pars tuberalis
• Photorefractoriness and circannual rhythms

3
Seasonal Rhythms

• In the course of a year, daily rhythms of
  behaviour follow fluctuations of daylength
• Environmental changes at increasing latitude,
  e.g.
• Photoperiod
• Temperature
• Food availablitity
• Many species adapt physiology in anticipation of
  these changes and to increase survival of their
  offspring
• Photoperiod is the most accurate environmental
  indicator of seasonal time

Brandstätter and Ackerl, unpubl.
4
Seasonal Physiological Rhythms

• Photoperiodic regulation of seasonal physiology
  in lab conditions

Brandstätter, unpubl. data
5
Seasonal Reproduction and Prolactin / Moulting
rhythms are synchronsed differently in diferent
mammals
Open circles Testis volume
Shaded area Mating season
Closed circles Plasma prolactin
6
Timing of Seasonal Reproduction
NB Timing of reproduction governed by length of
gestation
7
Circannual Rhythms
Testis Diameter (mm) Filled Circles
Plasma Testosterone (ng/ml) Open Circles
Almeida Lincoln 1984

• Occur in long-lived seasonal species (e.g. sheep)
• Occur in constant photoperiod (i.e. endogenous
  control)
• Equatorial species
• Melatonin target tissues?
• Photoperiod entrains circannual rhythms to annual
  cycle

8
Seasonal Changes in Gonadotrophin Releasing
Hormone (GnRH) Secretion
9
The Photo-neuroendocrine System

• Pineal melatonin is a key hormonal clock output
• Melatonin is synthesised and secreted at night
• Rhythmic melatonin secretion is driven by a
  poly-synaptic output pathway from the
  suprachiasmatic nuclei (SCN)
• Release of noradrenaline (NA) stimulates pineal

Moore 1996
10
The Photo-neuroendocrine System Pineal
Regulation by Photoperiod
Syrian hamster
Soay sheep
Maywood et al 1993
Hazlerigg et al 2004
11
Melatonin Biosynthesis

• Synthesised from tryptophan
• Key rate-limiting enzyme in melatonin
  biosynthesis is arylalkylamine-N-acetyltransferase
  (AA-NAT)
• AA-NAT activity is stimulated by noradrenergic
  stimulation of the pineal gland (output from the
  SCN)

Arendt 1995
12
Species Differences in Mammalian AA-NAT Regulation
Coon et al 1995
Borjigin et al 1995
13
How does Changing Photoperiod Regulate Physiology?

• In mammals, Melatonin is essential for
  photoperiodic time measurement
• Removal of pineal blocks responses
• Melatonin infusion experiments have been done to
  determine how changing melatonin secretion
  controls reproductive activation

14
Timed Infusion Experiments in PinX Hamsters
4
saline, 16 h
MEL, 8 h
MEL, 16 h
2
Paired testis weight (g)


0
Alternate day/night
Nightly
15
Decoding the Melatonin Signal

• Importance of melatonin signal parameters
  investigated in pinealectomised hamsters
• Carefully controlled melatonin signals imposed by
  timed injections/infusions
• Key parameter is melatonin signal duration
• Long duration melatonin short day response
• Short duration melatonin long day response

16
Where how does melatonin act?
17
Receptor autoradiography
Helliwell and Williams 1992
Modified from Wittkowski et al 1992
18
Melatonin Receptors

• Major mammalian subtypes MT1 and MT2 (previously
  Mel1a and Mel1b)
• G-protein-coupled receptors
• MT1 receptors implicated in seasonal
  neuroendocrinology
• Strong expression
• Absence of functional MT2 in hamsters
• Melatonin receptors expressed in many
  neuroendocrine tissues

Reppert 1997
19
Melatonin Target Sites in the Brain

• Most species express melatonin receptors in
  multiple brain structures
• Much inter-species variation
• Two major candidate sites for effects on
  reproductive activation
• 1 - Mediobasal hypothalamus (MBH)
• 2 - Pars tuberalis (PT)

20
The Case for the MBH
21
Mediobasal Hypothalamus Lesion (hamster)
Melatonin Infusion
Photoperiod Change
Open circle MBH-X Filled circle Sham control
Maywood and Hastings 1995
22
Mediobasal Hypothalamus Lesion (sheep)
Lincoln 2002
23
Summary of Mediobasal Hypothalamus Lesion Studies

• Attenuate effect of photoperiod (and melatonin
  infusion) on reproductive status and body weight
• No obvious effect on prolactin secretion
• Is prolactin regulated via a separate melatonin
  target site (e.g. the PT)?

24
The Case for the PT
25
Receptor autoradiography
Helliwell and Williams 1992
Modified from Wittkowski et al 1992
26
?TSH is photoperiodically regulated in the sheep
PT
Hanon et al, 2008 Current Biology
27
Functional TSH-receptors in the sheep
neuroendocrine system
Hanon et al, 2008 Current Biology
28
Photoperiodic DIO2 regulation explains springtime
need for T4 in the sheep basal hypothalamus
Hanon et al, 2008 Current Biology
29
?TSH and DIO2 are both induced in first 10 days
following transfer to Long Days
Hanon et al, 2008 Current Biology
30
TSH rapidly induces DIO2 expression in sheep
hypothalamus
ME / PT primary culture, 3-h
Icv Infusion to SP sheep, 5-days
Hanon et al, 2008 Current Biology
31
GnRH Neurosecretory Cell
T3
T3
Melatonin
Tanycyte
TSH
PT Thyrotrophs
Tuberalin?
PD Endocrine Cells
FSH, LH, Prolactin
32
Tuberalis uber alles model
Classical 2 site model
Morgan Hazlerigg, 2008 J Neuroendocrinology
33
Selected Further Reading

• Paul et al (2008) Phil Trans Roy SocB 363341
• Morgan Hazlerigg (2008) J Neuroendocrinol
  20820
• Hanon et al (2008) Current Biology 181147
• Hazlerigg Loudon (2008) Current Biology 18R795