Environmental Light, Circadian Rhythm and Breast Cancer

Question 1

What has occurred to humans now that artificial lighting has been introduced?

Answer 1

Humans have spent extended periods of time exposed to artificial light (a new spectral composition), while spending less time being exposed to natural sunlight and darkness we evolved with.

Question 2

Why is artificial light a problem?

Answer 2

• blue 480nm is needed to make serotonin but inhibits melatonin production
• 295nm UVB is needed to make Vitamin D
• artificial light is lacking this wavelength of the broad spectrum noon sun

Question 3

Why does the wavelength 480nm have to be absent to produce melatonin?

Answer 3

• at this wavelength, seratonin is produced

- it has to be absent because light inhibits the production of melatonin

Question 4

What are circadian rhythms?

Answer 4

• physical, mental and behavioral changes that follow a roughly 24-hour cycle
• responds primarily to light and darkness in an organism’s environment
• usually endogenously generated and self-sustaining

Question 5

Where are circadian rhythms found?

Answer 5

In most living things, such as animals, plants and many tiny microbes

Question 6

What are the two ways light acts on the body?

Answer 6

• the primary optic tract governs sight and and responses

- the retinohypothalamic tract is most sensitive to blue light stimulation energy in the wavelength of roughly 459-485nm

Question 7

What is the primary optic tract responsible for?

Answer 7

• visual effects

- visual reflexes

Question 8

What is the Retinohypothalamic tract responsible for?

Answer 8

Acute and longer-term biological/behavioral effects

• acute effects include melatonin secretion
• longer-term effects include circadian regulation

Question 9

What does light signal through?

Answer 9

The melanopsin protein
- it undergoes a chemical change when exposed to light received by intrinsically photosensitive retinal ganglion cells in the back of the eye

Question 10

What are some health effects of the deregulation of the circadian clock?

Answer 10

1. insomnia and sleep disorders
2. reduced alertness
3. poor cognitive and motor function
4. depression, bipolar disorder and seasonal affective disorder
5. cardio-vascular disease
6. altered hormone levels
7. obesity
8. early-onset diabetes
9. altered immune function
10. cancer - breast, prostate and colon

Question 11

What does the retinohypothalamic tract govern?

Answer 11

The circadian, endocrine and neurobehavioural functions

Question 12

What hormones relate to breast cancer and the hypothalamus exposure to light?

Answer 12

• GnRH
• Estrogen
• Progesterone
• Melatonin
• Serotonin
• Vitamin D (Calcitriol)

Question 13

What is melatonin?

Answer 13

• the darkness hormone
• secreted only at night (need absence of 480nm light)
• its precursor is serotonin
• secreted into the blood by the pineal gland to initiate sleep

Question 14

Why do melatonin levels vary in a daily cycle?

Answer 14

It allows the maintenance of the circadian rhythms of many biological functions

Question 15

How does the suprachiasmatic nucleaus (SCN) work?

Answer 15

It works like a clock.

• exposure to first light: the clock in SCN begins performing functions like raising body temperature and releasing stimulating hormones like cortisol
• delays release of hormones such as melatonin until later when darkness arives

Question 16

What is serotonin?

Answer 16

It’s a neurotransmitter that can also function as a hormone

• highest levels in the afternoon (need 480nm light)
• derived from tryptophan (constituent of most protein-based foods)

Question 17

Where is serotonin produced?

Answer 17

• most is produced in the gut, but the remainder is produced in the central nervous system where it functions to regulate mood, appetite, memory and sleep

Question 18

What is Vitamin D essential for?

Answer 18

The formation of normal bones and teeth by maintaining blood levels of calcium and phosphorus but also cell differentiation and development

Question 19

What are some other names for Vitamin D?

Answer 19

• Any of the fat soluble vitamins: D1, D2, D3

- calcitriol = active vitamin D

Question 20

Why is Vitamin not considered a true vitamin but a hormone?

Answer 20

We make most of it (~90%) from a metabolite of cholesterol that is present in the skin when exposed to UV light

• then further processed in the liver and kidneys
• also can be obtained in our diet (milk products and fatty fish)

Question 21

Where are vitamin D receptors found?

Answer 21

• bone
• kidney
• gut
• immune cells
• testis
• breast

Question 22

Why is vitamin D important in cancer?

Answer 22

It signals for antiproliferation

Question 23

How is breast cancer and the hormones associated?

Answer 23

Breast cancer has been found to be associated with low levels of melatonin, serotonin and vitamin D

Question 24

What environmental changes have been associated with the increased risk of chronic diseases like cancer?

Answer 24

• disruption of biological rhythms (daily, monthly, seasonally) alters hormones
• the new “built indoor environment”/artificial light which alters the exposure to natural sunlight and darkness
• geological location and population differences also affect the exposure to light (different latitudes and living in cities/rural areas)

Question 25

What is the exposure to LAN associated with?

Answer 25

- Light at Night (LAN) | - it is correlated with breast and prostate cancer

Question 26

Why is the shift to darkness such a key factor?

Answer 26

- It's a key factor in the production of melatonin and sleep regulation - exposure to light at night diminishes melatonin production - since light stimulates serotonin production, altered levels may lead to low levels of melatonin

Question 27

What is the relationship between breast cancer, light and circadian rhythm?

Answer 27

- changes in exposure to light affects biological rhythms, which alters teh metabolism of key hormones (includes GnRH, estrogen, progesterone, testosterone, vitamin D and melatonin) - alters neurotransmitters including dopamine and serotonin - alters micronutrients including iron These changes all increase the risk for chronic disease including breast cancer

Question 28

Summarize the problem with decreased natural daytime light and increased artificial light exposure.

Answer 28

Decreased natural daytime light exposure and increased artificial light exposure at night leads to an increased risk of breast cancer

Question 29

What is the rate limiting step in the melatonin biosynthesis in the pineal gland?

Answer 29

5HT, serotonin to N-acetylserotonin (NAS) | - the process starts with tryptophan and ends with melatonin (N-acetyl-5-hydroxytryptamine)

Question 30

Are Vitamin D levels also circadian?

Answer 30

Yes, like serotonin and body temperature, the serum concentration of vitamin D peaks after mid-day

Question 31

What is the role of Vitamin D?

Answer 31

- regulates calcium absorption | - has important effects on cell longevity and immune functions

Question 32

What are the three essential elements in our biological clocks?

Answer 32

1. A central oscillator that keeps time in the SCN 2. The ability to sense time cues from the environment and to reset the clock as the seasons change; and varying light cues 3. A series of outputs tied to distinct phases of the oscillator that regulate activity and physiology

Question 33

Define the period of in Circadian clocks

Answer 33

The time to complete one cycle (top of one peak to the next peak)

Question 34

Define the amplitude of rhythm in Circadian clocks

Answer 34

One half of the peak-to-trough distance (one wave is 2 amplitudes)

Question 35

What is a phase defined in?

Answer 35

Zeitgeber time (ZT)

Question 36

What is Zeitgeber time?

Answer 36

Zeitgebers are cues and can be any stimulus that imparts time information to the clock - have the ability to entrain the clock

Question 37

Where does the central clock reside in mammals?

Answer 37

In the suprachiasmatic nucleus (SCN), which is a small region in the hypothalamus of the brain that contains ca. 20000 neurons

Question 38

What are the roles of the SCN?

Answer 38

- produces a rhythmic output that consists of a multitude of neural and hormonal signals that influence sleep and activity - signals set the peripheral clocks present in the body

Question 39

How is the SCN clock reset? And what is it sensed by?

Answer 39

- by external light of specific wavelengths | - this is sensed by the ganglion cells of the retinal and carried by the RHT

Question 40

When is the major anabolic period for estrogen?

Answer 40

Between 6-9am

Question 41

What does the central clock of the SCN control?

Answer 41

- rest/activity rhythms | - entrained on a daily basis by the dark/light circle

Question 42

When does estrogen and testosterone peak?

Answer 42

During the rest period in humans

Question 43

What is the reverse transcript of erythroblastosis gene-alpha (Rec-erb-alpha)?

Answer 43

A nuclear receptor oncogene | - first discovered in the 1980s

Question 44

What is the ligand for Rev-erb-alpha? What does the receptor-ligand combination do?

Answer 44

- heme - this receptor ligand combination inhibits and fine tunes the clock, allowing the anabolic processes controlled by estrogen and testosterone to move forward