Androgens and Anti-Androgens Flashcards
What regulates androgen production in the testes?
Leydig cells in the testes turn cholesterol into testosterone.
LH regulates the initial step in this process, by binding to LHr. This stimulates intracellular signalling pathways which promotes:
cholesterol transport into mitochondria
transcription of testosterone biosynthesis genes
What do Testosterone and dihydrotestosterone bind to?
Where are weak acting androgens produced + 2 examples, how do they bind to testosterone receptors + what can they also be converted into?
Testosterone + dihydrotestosterone can bind to cell receptors + regulate protein expression.
Weak acting androgens are produced in zona reticularis of adrenal glands eg dehydroepiandrosterone, androstenedione.
Weak acting androgens bind to testosterone receptors w weaker affinity - but can also be converted to testosterone in the peripheral tissues if produced at high amounts
What is the male dominant sex steroid?
Effects it has on sertoli cells, what can it be converted into?
Testosterone is the male dominant sex steroid. functions:
- promotes spermatogenesis in Sertoli cells
- stimulates AMH & Inhibin B release from Sertoli cells –> Mullerian duct regression + neg feedback to ant pituitary
Testosterone is converted to DHT in males by 5AR (absent in females)–> secondary sex characteristics
What is the female dominant sex steroid?
2 functions
What happens to oestrogen sensitivity before and after puberty?
Oestrogen = dominant sex steroid in females
- It stimulates folliculogenesis
- Develops female secondary sex characteristics
Before puberty, the hypothalamus & ant pituitary are v sensitive to neg feedback from testosterone + oestrogen.
Sensitivity decreases in puberty to allow more steroid production for sexual development
How are testosterone and DHT linked?
what do they both bind to - but how are they different
2 functions of DHT - therefore how R these pharmacologically EXPLOITED?
What can Inadequate DHT metabolism cause?
In most target cells (excluding myocytes), testosterone is converted to DHT by 5-alpha-reductase
Testosterone and DHT both bind to the same nuclear receptor, but the testosterone-receptor complex is less stable. Therefore DHT formation amplifies actions of testosterone
DHT increases prostate growth- blocking 5AR used in prostate cancer
DHT linked w hair loss - 5AR inhibitors treat male pattern baldness
Inadequate DHT metabolism may cause BPH, acne & hirsutism
What are the types of DHT?
5-alpha reductase converts testosterone to DHT
- Type I is found in the scalp & skin
- Type II in the genital skin & prostate
3 effects of testosterone? + how they r used clinically
- Develops secondary male sex characteristics
- Induces bone & muscle growth - hence anabolic steroids (mimic testosterone) can treat osteoporosis & muscle wasting diseases
- Stimulates EPO secretion, hence anabolic steroids used for anaemia
Several androgens (e.g. testosterone, nandrolone, oxymetholone and stanozolol, etc.) are used for prolonged periods and their continuous use can cause adverse effects
5 negative effects of androgens?
- Hypertension & oedema - steroids retain Ca, Na & water
- Cholestatic jaundice- anabolic steroids linked w liver cancer
- Neg feedback reduces LH and FSH, leading to less spermatogenesis and testicular regression
- Gynaecomastia – excess androgens converted to oestrogens by aromatase
- Other effects: virilisation in females, hirsutism, male pattern baldness, acne, premature epiphyseal closure in children, headaches, anx/depression, decreased glucose, acute renal failure.
3 key characteristics of a nuclear receptor? ( LDA)
What are the 3 actvation steps for Ligand Activated Transcription Factors?
Ligand binding to its binding site causes shift in a-helix
Receptor dimerises, moves into nucleus + binds to specific DNA sequences
This causes recruitment of DNA modifying enzymes e.g. histone deacetylases, other transcription factors & RNA polymerase to form promoters of hormone responsive genes.
What type of genes are hormone responsive?
how many nuclear receptors genes do humans have + how is it a super family?
Hormone responsive Genes inc:
Functional tissue specific genes
Tissue development & differentiation genes
Cell cycle & proliferation genes
There are 48 nuclear receptor genes in humans
All share a common domain structure that is activated by ligand binding
What are the main steroid receptors and their ligands?
4 sexual dimorphisms between males & females?
BMR, upper/ lower body strength, 3 things men have larger, brain
Average BMR ~6-10% percent higher in males than females
Females have ~40–60% the upper body strength of males & 70–75% lower body strength, smaller hearts, trachea, lungs
Testosterone acts on the brain- behavioural changes
(Differences in brain physiology ≠ differences in intellect)
6 effects of testosterone & DHT on secondary characteristics between males and females?
Males have: ~
Greater muscularity, esp shoulder girdle
Stronger bone growth, greater shoulder to pelvic girdle ratio (GH secretion)
Heavier skull, larger hands & feet
Deep voice due to increase growth of larynx
Pubic hair continuous w abdo and chest hair
Prominent subcutaneous veins due to lack of SC fat
Describe the production and function of androgens in females
what can testosterone insufficiency in menopausal females lead to?
key function of androgens?
Androgens produced by adrenal, ovarian & adipose tissues but circulate at lower levels than males.
AR maintains follicle health during ovulation.
In the female brain, androgens regulate sexual activity, libido & mating behaviour.
Testosterone insufficiency in menopausal females–> low libido, fatigue, hair loss, osteopenia, osteoporosis & decreased body mass.
A key function of androgens = aromatisation to estrogens
What are the other effects of testosterone and steroids?
3 main ways in which prostate cancer is treated?
Abiraterone acetate: Block androgen at receptors, preventing prostate growth. Useful in BPH & PC
Anti-androgens (flutamide, Bicalutamide, Enzalutamide, Nilutamide): compete w testosterone + DHT, blocking their action
5AR inhibitors (finasteride & dutasteride): suppress DHT mediated prostate cell expansion
