PHRM 825 Lecture 11- Androgens

what cells produce a majority of testosterone

Leydig cells

plasma levels of testosterone in men and women

men: 0.6 ug/dL

women: 0.03 ug/dL

explain the regulation of testosterone synthesis

hypothalamus releases GnRH --> anterior pituitary releases LH --> Leydig cells are activated and produce testosterone

what is the role of 5a- reductase in testosterone

converts testosterone to 5a-dihydrotestosterone which is the more potent and active androgen

inactive forms of testosterone ready to be excreted

androsterone and etiocholanolone

intermediates in testosterone synthesis pathway

produced in adrenal glands

weak androgen effects

androstenedione

dihydroepiandrosterone (DHEA)

dihydroepiandrosterone sulfate (DHEAS)

physiological effects of testosterone

growth promoting properties

stimulation of sexual function

stimulation of erythrocyte production

decrease in HDL levels

clinical uses of androgens

-androgen replacement therapy

-gynecologic disorders- endometriosis or postmenopausal symptoms

-protein anabolic agents

-andropause

synthetic androgens

-methyltestosterone

-testosterone enanthate

-testosterone propionate

-testosterone cypionate

17-alkyl form

more active orally

methyltestosterone

ester forms

prolonged absorption time and greater activity for IM administration

testosterone propionate, enanthate, cypionate

health risks from anabolic steroid use in sports

harmful changes in cholesterol

acne

high BP

hepatic dysfunction

testicular atrophy

block conversion from testosterone to 5a-dihydrotestosterone

5a-reductase inhibitors

block the binding of endogenous androgens to the receptor

steroidal and non steroidal

Androgen receptor antagonists

5a-reductase inhibitor

benign prostatic hyperplasia, male pattern baldness, hirsutism in women

Finasteride

5-alpha reductase inhibitor

benign prostatic hyperplasia

male pattern baldness

Dutasteride

steroidal androgen receptor antagonist

hirsutism in women

excessive sexual drive in men

Cyproterone acetate

steroidal androgen receptor antagonist

hirsutism in women

acne

Spironolactone

non-steroidal androgen receptor inhibitor

prostate cancer

flutamide

non-steroidal antiadrogen

metastatic castration-resistant prostate cancer

enzalutamide