5. Hormones and cancer Flashcards
What are the different types of hormones?
- Peptides
- steroids
- Amine
What is De novo synthesis and give examples where it occurs?
When complex molecules are constructed from simple molecules instead of from partial degradation then recycling. e.g. cholesterol production in the liver
What are steroid hormones and how are they produced?
Steroid hormones help control metabolism, inflammation, immune functions, salt and water balance, development of sexual characteristics, and the ability to withstand illness and injury.
Steroid hormones are made using cholesterol (which can come from diet or made by liver) and made into steroids in the steroid-producing cells in adrenal glands and gonads.
What are the types of steroids?
- Androgens - sexual development in male
- oestrogens - sexual development in female
- glucocorticoids - regulate glucose homeostasis
- mineralocorticoids - regulate water and electrolyte balance
- progestins - prevent pregnancy by inhibiting ovulation
What are steroid hormones used for?
They have high hydrophilicity so can cross membrane and bind to intracellular receptors- a type of these would be nuclear receptors AKA transcription factors so steroid hormones can bind to TFs and affect gene expression and protein production
What are the downsides of exogenous hormones?
Diethylstilbestrol (form of oestrogen) was used to decrease miscarriage risk in prego women but increased breast cancer risk and vaginal/cervical cancers in daughters.
Combines menopausal therapy (progestin and oestrogen) increased risk of endometrial cancers and only given to those with hysterectomy
Early exposure to oestrogen e.g. early puberty, late menopause, late/no first pregnancy risk breast cancer
Insulin is associated with higher risk of kidney, stomach, pancreatic, liver and respiratory cancer. Insulin-like growth factors (IGFs) are associated with prostate, breast and bowel cancers.
How does ERalpha interact with ERE?
In the nucleus, ERa interacts with EREs and recruits coactivators such as steroid receptor coactivators such as SRC-1 in the p160 family, which then recruit CREB binding protein in the p300 family which has intrinsic histone acetyltransferase (HAT) activity. This histone acetylation near the ERE opens up the chromatin and facilitates RNA polymerase II transcription. RNA polymerase II is then phosphorylated by coactivators to form an elongation-competent form.
How does ERE independent signalling work?
ERE-independent signalling also occurs wherein ER does not bind to the DNA itself, but interacts with transcription factors such as SP1 and AP1.
Name 2 exocrine glands
The breast and prostate are both exocrine glands meaning they secrete substances outside of the body via ducts. 90% of breast and prostate cancers occur in the luminal epithelial layer and they can be diagnosed by a loss in the basal cell layer. The breast and the prostate both consist of several branching glands and secrete fluids out of the body via the nipple or urethra.
What effects does ERalpha and ERbeta signalling have on both men and women?
ERa and ERb are expressed on different parts of the body and can have opposing effects if they are present on the same cells.
In women, oestrogen signalling is important for the growth and development of the uterus, fallopian tubes, vagina and breasts. It is also responsible for the moulding of body contours and the pubertal growth spurt in long bones and epiphyseal closure.
In men, oestrogen signalling contributes to the growth spurt, skeletal maturation and epiphyseal closure.
How is menstrual cycle controlled by hormones?
The menstrual cycle is controlled by the neuroendocrine system as follows:
· GnRH is released from the hypothalamus
· LH and FSH secretion from anterior pituitary stimulated
· FSH and LH stimulates growth and maturation of ovarian follicles and FSH stimulates oestrogen release
· LH induces ovulation and transforms the granulosa into the corpus luteum which is an actively secreting gland
· Ovaries produce oestrogen and progesterone which negatively feedback onto hypothalamus and pituitary.
Symptoms of breast cancer include:
· New lump in breast tissue
· Swelling of the breast
· Skin irritation and dimpling
· Breast or nipple pain
· Nipple retraction
· Nipple discharge
· Redness, flaking, or thickening of nipple or breast
The genes with familial mutations associated with breast cancers include:
BRCA1 and BRCA2 – key roles in DNA repair and cell cycle
ATM – gene underlying ataxia-telangiectasia
BARD1 – regulates cell apoptosis
how are breast cancers detected?
Breast cancers are detected through screening (e.g. mammography, MRI) and diagnostic tests (e.g. biopsies) and monitoring tests are used to assess the effect of the treatment.
How are they treated?
ER+ breast cancer was initially treated using oophorectomy until drugs modulating the oestrogen receptor were developed including:
· Synthetic steroidal and non-steroidal oestrogens
· Anti-oestrogens (antagonists)
· Non-ER-modulating drugs (aromatase inhibitors)
Anti-oestrogen drugs include the selective oestrogen receptor modulator (SERM) Tamoxifen and the selective oestrogen down-regulator (SERD) Fulvestrant.
