Hormones and cancer – Depypere
1. Estrogen steroid hormone
17-β-oestradiol, tibolone: steroid bind to receptor as a co-activator and binds DNA
on every cell -> penetrate every membrane to the nucleus => important
regulator
- Estradiol = estrogen steroid hormone
- Produced by the ovaries
o Production by the follicle from menarche to menopause (51-52y)
- Inserted into receptor when OH-group is in cytoplasm and nuclear, dimeric
complex
- Complex will migrate to the DNA -> oestradiol will bind to oestrogen
receptor on the DNA binding -> recruitment repressor for transcription of
DNA for making proteins, collagen, elastin
o Different co-activators and repressors in every patient
- Oestradiol is an agonist that regulates also bone in men
- Oestradiol is a regulator of many things:
o Reproduction – sexual development – cycle – libido
o Skin, hair, eyes
o Mucosa, bone, gut
o Blood vessels, liver function
- Hormonal cycle
o Immature eggs with granulosa cells -> production estradiol
o Oocyte will release when there is a high concentration of estradiol
o Follicles mature by brain FSH to maintain growth (during puberty)
and multiply controlled by hypothalamus
o Endometrial layer changes due to lower hormone levels
o Glands that get deeper: secrete sugar rich fluid for the fertilized egg
to implant in the membrane
- Cells produce estradiol and bind it to proteins low % free form in the
bloodstream -> migrate to capillaries into interstitial fluid of the body
- No estrogen blood vessel get stiff with older women -> pump blood to
raise the blood pressure
Anti-oestrogen drugs - tamoxifen, raloxifene: hormones secreted though glands
trough the bloodstream -> target other organs
1.1 Bone and estrogens
Bone structure
- Trabecular bone
o Spongy
o Favours flexibility
o 20% of bone mass
- Cortical bone
o Compact
o Offers stiffness and biomechanical strength
o 80% of bone mass
1
, - Osteoclasts and osteoblasts
o Essential to maintain bone quality and bone mass
o Osteoclasts: resorb old/damaged bone
o Osteoblasts: make new bone after they got resorbed by the
osteoclast
o Collagen production to form new bone
Bone
- Renewal of the bone: gravity stimulates cells by exercising to become
strong bone => no gravity loose bone
- Changes in bone mass according to cycle of life
o At 25 there is a peak and then decrease but faster in women due to
the decrease in hormone levels -> dead due to osteoporosis
- Osteoporosis = disease of disturbed strength of the bone
o Exposes millions of women to a higher risk of bone fractures, with
life threatening consequences
o Underestimated and prevalent diseases
- Fractures along all sites of the skeleton also increase with age
o Hipfractures
Almost 20% of patients die within the first year after a
hipfracture
>50% will not be able to walk without help within 1year
Although hipfractures compose only 14% of all fractures ->
responsible for 72% of costs of all fractures
o Osteoporotic fractures
1 in 3 women > 50y
2. Breast cancer
2.1 Anatomy
- Apocrine gland producing breast milk
- 15-20 lobes: glandular tissue
- Glandular tissue, fat, connective tissue, blood vessels, important lymphatic
system
- Up to 40 lobules in one lobe
o Lobulus evolve with different stages in life: puberty, menstrual cycle,
pregnancy, lactation, menopause, …
o Dens lymphatic system, superficial and peri-areolar drain, …
Hormones being produced at puberty
- FSH -> stimulate follicles -> growth estrodial -> bloodstream to nipple to
form breast -> gland divide and grow -> side branches for lactation of milk
formed
2
1. Estrogen steroid hormone
17-β-oestradiol, tibolone: steroid bind to receptor as a co-activator and binds DNA
on every cell -> penetrate every membrane to the nucleus => important
regulator
- Estradiol = estrogen steroid hormone
- Produced by the ovaries
o Production by the follicle from menarche to menopause (51-52y)
- Inserted into receptor when OH-group is in cytoplasm and nuclear, dimeric
complex
- Complex will migrate to the DNA -> oestradiol will bind to oestrogen
receptor on the DNA binding -> recruitment repressor for transcription of
DNA for making proteins, collagen, elastin
o Different co-activators and repressors in every patient
- Oestradiol is an agonist that regulates also bone in men
- Oestradiol is a regulator of many things:
o Reproduction – sexual development – cycle – libido
o Skin, hair, eyes
o Mucosa, bone, gut
o Blood vessels, liver function
- Hormonal cycle
o Immature eggs with granulosa cells -> production estradiol
o Oocyte will release when there is a high concentration of estradiol
o Follicles mature by brain FSH to maintain growth (during puberty)
and multiply controlled by hypothalamus
o Endometrial layer changes due to lower hormone levels
o Glands that get deeper: secrete sugar rich fluid for the fertilized egg
to implant in the membrane
- Cells produce estradiol and bind it to proteins low % free form in the
bloodstream -> migrate to capillaries into interstitial fluid of the body
- No estrogen blood vessel get stiff with older women -> pump blood to
raise the blood pressure
Anti-oestrogen drugs - tamoxifen, raloxifene: hormones secreted though glands
trough the bloodstream -> target other organs
1.1 Bone and estrogens
Bone structure
- Trabecular bone
o Spongy
o Favours flexibility
o 20% of bone mass
- Cortical bone
o Compact
o Offers stiffness and biomechanical strength
o 80% of bone mass
1
, - Osteoclasts and osteoblasts
o Essential to maintain bone quality and bone mass
o Osteoclasts: resorb old/damaged bone
o Osteoblasts: make new bone after they got resorbed by the
osteoclast
o Collagen production to form new bone
Bone
- Renewal of the bone: gravity stimulates cells by exercising to become
strong bone => no gravity loose bone
- Changes in bone mass according to cycle of life
o At 25 there is a peak and then decrease but faster in women due to
the decrease in hormone levels -> dead due to osteoporosis
- Osteoporosis = disease of disturbed strength of the bone
o Exposes millions of women to a higher risk of bone fractures, with
life threatening consequences
o Underestimated and prevalent diseases
- Fractures along all sites of the skeleton also increase with age
o Hipfractures
Almost 20% of patients die within the first year after a
hipfracture
>50% will not be able to walk without help within 1year
Although hipfractures compose only 14% of all fractures ->
responsible for 72% of costs of all fractures
o Osteoporotic fractures
1 in 3 women > 50y
2. Breast cancer
2.1 Anatomy
- Apocrine gland producing breast milk
- 15-20 lobes: glandular tissue
- Glandular tissue, fat, connective tissue, blood vessels, important lymphatic
system
- Up to 40 lobules in one lobe
o Lobulus evolve with different stages in life: puberty, menstrual cycle,
pregnancy, lactation, menopause, …
o Dens lymphatic system, superficial and peri-areolar drain, …
Hormones being produced at puberty
- FSH -> stimulate follicles -> growth estrodial -> bloodstream to nipple to
form breast -> gland divide and grow -> side branches for lactation of milk
formed
2
