Androgens Flashcards
Hypothalamic “releasing hormones” target the…
Anterior pituitary
Pituitary “stimulating hormones” target…
Various systemic organs and glands
Hormones released by the
- Anterior pituitary
- Posterior pituitary
- GH, TSH, ACTH, LH, FSH, PRL
2. ADH, oxytocin
Negative feedback
Elevated levels of hormones inhibit further release from hypothalamus and anterior pituitary
Regulates release of hormones to prevent over stimulation of target tissues
3 classes of gonadal hormones
Androgens (ex: testosterone)
Estrogens (ex: estradiol)
Progestins (ex: progesterone)
3 hormones that regulate gonadal hormones
Gonadotropin-releasing hormone (GnRH - from hypothalamus) Luteinizing hormone (LH - from pituitary) Follicle-stimulating hormone (FSH - from pituitary)
Pulsate vs Constant release of GnRH
Pulsate: stimulates release of LH and FSH from pituitary (normal activity)
Constant: inhibits secretion of LH and FSH (down regulation and desensitization of GnRH receptors)
LH
function and location
Stimulates testosterone production in the Leydig cells in the testes
FSH
function and location
Stimulates spermatogenesis in Sertoli cells of the testes
Inhibins
Produced by Sertoli cells
Inhibits FSH production
Testosterone
from blood to cell
Circulates in blood bound to sex hormone binding globulin (can only pass through membrane when it is unbound)
Enters target cells and binds to intracellular androgen receptors (normally bound to heat shock proteins, will dissociate when test binds)
AR forms a dimer and translocates to the nucleus
Initiates gene transcription
Sex hormone binding globulin
The way testosterone is transported in the blood
But testosterone can only pass into cells when it is unbound
Testosterone can be converted to ____ by ____
what other male sex hormone
5alpha-dihydrotestosterone (DHT)
In target tissues
By 5alpha-reductase
DHT
5alpha-dihydrotestosterone
More potent agonist of the androgen receptor
Testosterone can be converted to what other hormone? By what enzyme?
Small amounts can be converted to estrogen
Done by aromatase, whose levels are higher in adipose tissue
What tissues are affected by:
- Dihydrotestosterone (4)
- Testosterone (4)
- Estradiol (2)
- External genitalia, skin, hair, prostate
- Muscle, bone marrow, bone, brain
- Bone, brain
Cortisol
Causes negative regulation of sex hormones
Produced in the adrenal gland
Decrease testosterone levels in men (from inhibition of GnRH secretion)
Inhibit ovulation in women (from suppression of LH, estrogen and progestin secretion)
Hypogonadism
Diminished functional activity of the gonads
Can be congenital or acquired
Symptoms: low sex drive, erectile dysfunction, mood disturbances, fatigue and sleep disruptions, delayed sexual development
Testosterone
- Lipid or water soluble
- High or low oral bioavailability
- Lipid
2. Low (metabolized by the liver before entering systemic circulation)
Testosterone enanthate
Ester derivative of testosterone
Used for androgen replacement therapy
Administered as an intramuscular injection
Highly lipophilic and diffuses slowly from injection site
Ester group is cleaved by cellular enzyme, then free testosterone enters systemic circulation
2 brand names used for androgen replacement therapy (and how they are absorbed)
- Androderm (transdermal patch)
- Striant (buccal system)
Both have direct absorption of testosterone into systemic circulation to avoid first pass
Anabolic steroids
Synthetic derivatives of testosterone
More anabolic (muscle building) than androgenic
Used by athletes to increase body mass, strength, and performance
Many designer drugs to escape detection in urine
Typically illegal due to many adverse effects
Benign prostate hyperplasia
Non-malignant
Symptoms may include urinary retention
Need androgen suppression therapy
Prostate cancer
Malignant, uncontrolled growth
High prevalence of metastasis
Need androgen suppression therapy
GnRH Analogs
Can act as agonists or antagonists
Pulsatile application can be used to increase FSH and LH to promote ovulation
Long term use overrides hypothalamic GnRH pulses (to decrease FSH and LH secretion, and test and estrogen secretion)
Leuprolin
GnRH analog
Non-pulsatile application used for precocious puberty and prostate cancer
Subcutaneous implantation of pellet
Undesirable initial “flare” of increased testosterone (antagonist given until levels drop)
GnRH Antagonist
Binds to and blocks GnRH receptor
Decreases LH and FSH and results in decreased testosterone levels
Degarelix
GnRH antagonist
Synthetic peptide that binds to GnRH receptor
Used to teat advanced prostate cancer
Does not cause initial flare like leuprorelin
3 points in time where the effects of androgens can be suppressed
- Testosterone biosynthesis
- Testosterone –> DHT conversion
- Androgen receptor
Ketoconazole
Antifungal
Can technically be used to suppress androgen levels (but not typically)
Spironolactone
Diuretic used for cardiac failure
Can technically be used to suppress androgen levels (but not typically)
Can block biosynthesis of testosterone from cholesterol
Finasteride
Similar structure to testosterone
Competes for binding to 5alpha reductase
Decreases the levels of DHT
Used to treat BPH (reduces prostate size and resolves urinary retention) and male pattern baldness
Flutamide
Synthetic, non-steroidal anti-androgen
Androgen receptor antagonist (competitive)
Used in combination with GnRH antagonists (leuprorelin) in prostate cancer
Cyproterone
Used to treat excess sex drive
Androgen receptor antagonist (competitive)
