Pituitary and Gonadal Hormones III Flashcards
Two cells located in the testis?
Sertoli
Leydig
Hypothalamic-Pituitary-testes axis :
LH produces what and in which cells?
FSH produces what and in which cells?
LH : Testosterone in Leydig cells
FSH : components needed for spermatogenesis (hormone binding protein/globulin or androgen binding protein) in Sertoli cells
Hypothalamic-Pituitary-testes axis :
Testosterone inhibits the release of what? (2)
GnRH
Gonadotropins
Sertoli cells produce what? (2) roles?
Inhibin : inhibits FSH release
Activin : stimulates FSH release
Testosterone is synthesized from which hormones? In which cells is it produced?
Free cholesterol
Pregnenolone
Leydig cells
What happens to testosterone adipose, liver and hypothalamus?
Converted to estradiol by aromatase
Where is testosterone degraded? Where is it secreted?
Liver
Urine
Testosterone is bound to what in circulation?
When it enters the cell, it is converted to what and with which enzyme?
Bound to SHBG
Converted into dihydrotestosterone
5a-reductase
Is dihydrotestosterone (DHT) and more potent or less potent agonist of the androgen receptor?
More potent
After testo. is converted to DHT and binds to receptor, what happens and where does it do?
Ligand-receptor dimerizes and translocates to nucleus to initiate transcription
What is the final action of testosterone (DHT) once it initiates transcription?
Induces metabolic changes:
- Increase lean body mass
- Increase liver synthesis of clotting factors
- Decrease HDL and hormone binding protein
3 clinical uses of androgens?
Male hypogonadism (low testosterone) Osteoporosis Postpartum reduction of breast, endometriosis and postmenopausal hormone replacement in women
Two types of male hypogonadism?
What are the symptoms? (4)
- Congenital
- Acquired
Delayed sexual development, low sex drive, erectile dysfunction, mood disturbances
Do androgens have low or high bioavailability?
Low
3 examples of drugs involved in androgen replacement therapy? How are they administered?
Testosterone enanthate : IM injectable
Androderm : Transdermal patch
Striant : Buccal system
2 types of anabolic steroids?
Testosterone
Oxymetholone
Androgen Suppression Therapy are effective in which cases? (6)
Precocious puberty Male pattern baldness Hypersexuality Transgender hormone therapy Benign Prostate Hyperplasia Prostate Cancer
2 GnRH analogs?
What is the MOA (initially (1) and more long-term (3) )
Nafarelin Leuprolide -Initially gonadotropin release is increased -Receptors are desensitized -Gonadrotropin release is decreased -Release of testosterone is decreased
How is leuprolide administered?
What is an undesirable effect and how is this treated?
As subcutaneous pellets
Undesirable initial flare (increase in testosterone)
AR antagonists are given until testosterone decreases
Example of GnRH antagonist? Where does it act?
Degarelix
Blocks GnRH receptors
What are the effects of Degarelix (GnRH antagonist)?
What disease does it treat?
Decreases gonadotropin release (decrease in testosterone levels)
-Advanced prostate cancer
Does Degarelix cause an initial flare and increase in testosterone like GnRH agonists?
No
2 Testosterone Synthesis suppressors?
Ketoconazole
Spironolactone
High doses of Ketoconazole inhibit _____ and _____ hormone synthesis
Adrenal
Gonadal
What is the MOA of ketoconazole?
Displaces DHT and estrogen from SHBP in plasma
What is the MOA of spironolactone?
Inhibits testosterone synthesis by reducing 17a-hydroxylase activity
(Competes with DHT for AR binding)
2 5a-reductase inhibitors?
5a-reductase
Finasteride
MOA of 5a-reductase?
Converts testosterone to more potent DHT
MOA of finasteride?
competes with testosterone for binding with 5a-reductase
food-derived substances that could inhibit 5a-reductase?
Saw Palmetto berries
2 androgen receptor antagonists?
Flutamide
Spironolactone
MOA of flutamide?
Used in combination with ________ in prostate cancer?
AR blocker
GnRH analogs
