Hormone Driven Breast Cancer Flashcards
What are endocrine disrupting compounds?
- chemicals in our environment that disrupt our hormones and increase our risk of chronic diseases like cancer
What does disruption of biological rhythms alter?
- our hormones and increases risk of chronic diseases
What is a major component of disruption to our environment?
- built indoor environment
- alters our exposure to natural sunlight and darkness with artificial light
- geographic location and population differences also factors
Why is indoor lighting a problem?
- new spectral composition
- relative to evolutionary timeline, very new and not adapted to
What wavelength do we need to make serotonin? melatonin? vitamin D?
- 480 nm serotonin
- absent 480nm melatonin
- 295nm UVB
What are circadian rhythms?
- physical, mental, and behavioural changes that follow a roughly 24 hour cycle
- responds primarily to light and darkness
- animals, plants, and many tiny microbes
What is the study of circadian rhythms called?
- chronobiology
What two pathways does light act on the body with?
- primary optic tract
- retinohypothalamic tract
What is the primary optic tract?
- governs visual perception and responses
What is the retinohypothalamic tract? What wavelengths is it sensitive to?
- governs circadian, endocrine and neurobehavioural functions
- most sensitive to blue light stimulation energy (459-485nm)
How is light signaled through the retinohypothalamic tract?
- light signals through melanopsin protein that undergoes a chemical change when exposed to light received by intrinsically photosensitive retinal ganglion cells
What are some health effects of circadian clock de-regulation?
- insomnia/sleep disorders
- reduced alertness
- poor cognitive and motor function
- depression
- cancer
- and more
What does the retinohypothalamic tract govern?
- circadian, endocrine and neurobehavioural functions
Which hormones relate to breast cancer and the hypothalamus exposure to light?
- GnRH
- estrogen
- progesterone
- melatonin
- serotonin
- vitamin D (calcitriol)
What is melatonin? When is it secreted? What is it’s precursor?
- “hormone of darkness”
- secreted at night into blood by the pineal gland to initiate sleep(levels vary in daily cycle)
- precursor is serotonin
What does the suprachiasmatic nucleus do when exposed to the first light?
- begins performing functions like raising the body temp and releasing stimulating hormones like cortisol
- delays release of other hormones lie melatonin
What is melatonin a regulator of?
- ERalpha and estrogen production
What are the steps in the melatonin biosynthesis in the pineal gland?
- starts with tryptophan
- rate limiting step: serotonin to N-acetylserotonin
- to melatonin
How does melatonin inhibit the estrogen response pathway?
- through binding to MT1
What is serotonin? Where is it synthesized?
- neurotransmitter and hormone
- functions to regulate mood, appetite, memory, and sleep
- most produced in cells of gut
- modulation of serotonin levels is the major action of many antidepressants
When are serotonin levels highest?
- highest in afternoon
What is needed to make serotonin?
- need wavelength of 480nm
- derived from tryptophan
What is the role of vitamin D in breast cancer?
- higher levels of vitamin D are associated with decreased risk for breast cancer
- low natural light exposure results in low vitamin D (suggests serotonin low as well)
What does vitamin D inhibit? Where does vitamin D inhibit?
- ERalpha and aromatase in the estrogen pathway
- COX-2 of the prostaglandin pathway
- acts in both cancerous breast epithelial cells and breast adipose fibroblasts surrounding the tumor (thus inhibits breast cancer cell proliferation)
In what 4 ways does vitamin D inhibit proliferation?
- induces cell expression of cell cycle arrest proteins and pro-apoptotic cell death proteins (Bax and Bak)
- suppresses inflammation by inhibiting inflammatory enzymes (COZ-2)
- decreases expression of aromatase (final enzyme in synthesis of estrogen)
- down-regulates the expression of estrogen receptor-alpha
How are melatonin and breast cancer related?
- exposure to light at night diminishes melatonin production
- exposure to light at night is correlated with breast and prostate cancer
What hormones are affected by changes in light and biological rhythms?
- GnRH
- estrogen
- progesterone
- testosterone
- vitamin D
- melatonin
What neurotransmitters are affected by changes in light and biological rhythms?
- dopamine and serotonin
What micronutrients are affected by changes in light and biological rhythms?
- iron
What changes in light increase breast cancer risk?
- decreased natural daytime light exposure
- increased exposure to light at night
What are the important effects of vitamin D?
- regulates calcium absorption, effects on cell longevity and immune functions
What conditions are characterized by low serotonin?
- depression
- seasonal affective disorder
- SSRIs: reduced breast cancer risk
How might low serotonin, vitamin D and melatonin result in breast cancer?
- low serotonin depress production of melatonin
- vitamin D activate transcription of initial serotonin-synthesizing gene tryptophan hydroxylase
- low vitamin D leas to low serotonin leading to low melatonin allowing increased estrogen signalling
