Androgens: 12 Flashcards
What is important to know about testosterone?
Most important androgen secreted by testis.
Average of 8 mg of testosterone produced daily.
-mostly by leydig cells
Plasma levels of testosterone in men is 0.6 mcg/dL after puberty – decreases after 50.
-in women it’s 0.03mcg/dL to make estradiol.
On average 0.6mcg/dL of testosterone is in the male blood stream, what is the breakdown of bound vs unbound?
65% is bound to SHBG (sex-hormone binding globulin).
33% is bound to albumin.
2% is free.
How is testosterone synthesis regulated?
The hypothalamus releases GnRH which stimulates the anterior pituitary to release LH and FSH.
LH will promote the production of testosterone in the testis by the leydig cells.
Too much testosterone production will inhibit GnRH, LH and FSH.
What is follicle stimulating hormone used for?
Released from the anterior pituitary, it works in the testis specifically on sertoli cells to create sperm.
Testosterone itself is a weak prodrug. What is it converted to?
In the ovaries and testis, aromatase will make ring 1 aromatic converting testosterone to 17B-estradiol.
In target tissues, 5a-reductase will remove the 3-4 double bond and add a hydrogen to make 5a-dihydrotestosterone. More potent and Major active androgen.
How is testosterone excreted?
In the liver it is inactivated and conjugated then excreted in the urine.
Changing 17B-hydroxyl group to ketone and remove the 3-4 double bond and add a hydrogen will inactivate the testosterone.
Inactive forms are androsterone and etiocholanolone.
What are the three adrenal androgens and their significance?
Androstenedione, DHEA and DHEAS.
They are intermediates of the testosterone synthesis pathway released into the bloodstream.
Produced in adrenal glands with weak androgen effects.
We think this is a reservoir our body uses when we need these hormones.
What are the physiological effects of testosterone?
Responsible for many of the puberty changes.
Growth promoting properties…
-Penile and scrotal growth
-Thicker and oilier skin
-Pubic, axillary and beard hair
-Deepening of the voice
-Skeletal growth followed by epiphyseal closure
-Increase in lean body mass (positive N balance)
Stimulation and maintenance of sexual function.
Stimulate erythrocyte production.
Decrease in HDL levels. (men more at risk for CV problems).
What are the clinical uses of androgens?
Androgen replacement therapy in men.
Gynecologic disorders.
Protein anabolic agents.
Andropause.
How are androgens used in androgen replacement therapy in men?
Male hypogonadism - testosterone deficiency
Hypopituitarism
-Still infertile due to lack of FSH
How are androgens used in gynecologic disorders?
Adverse effects possible
Endometriosis: uterine tissue growth outside uterus (use danazol as a weak androgen)
controversial but CAN be used with estrogens for replacement therapy in postmenopausal period.
-eliminate endometrial bleeding and enhance libido
How are androgens used as protein anabolic agents?
Reverses protein loss after trauma, surgery or prolonged immobilization along with dietary and exercise.
How are androgens used in andropause?
Since testosterone decreases after 50 in males you can intervene with testosterone.
Why is the methyltestosterone more orally active than other synthetic androgens?
Methyltestosterone has a 17a-methyl group making it a tertiary alcohol which cannot be converted to a ketone.
Why are the synthetic ester forms not administered orally?
Propionate, enanthate and cypionate all have prolonged absorption time and greater activity for IM administration.
The 17-ester increases Log P so it will remain at the injection site for long time and diffuse slowly and maintain levels in the body.
