Steroids Flashcards
What are Anabolic Steroids?
Small cholesterol based drugs related to the endogenous androgenic endocrine hormones, including testosterone.
What are two main important actions of steroids?
- Androgenic. 2. Anabolic.
What is the androgenic action of steroids?
Promotes male characteristics.
What is the anabolic action of steroids?
Promotes protein synthesis/build lean muscle mass.
What are endogenous steroid hormones? How do they work?
Small lipid-based hormones based on cholesterol. They activate intracellular receptors that act as hormone regulated transcription factors.
What do Glucocorticoids do?
They regulate inflammation and metabolism.
What do Mineralocorticoids do?
They regulate fluid and salt balance.
What do sex steroids do?
They regulate reproductive physiology, bone density, muscle mass, etc.
Where is testosterone produced?
Leydig cells in the testes.
What part(s) of the brain regulate the production of testosterone and the creation of sperm?
Endocrine signals from the hypothalamus/anterior pituitary,
When do Leydig cells synthesize testosterone?
When LH binds to the extracellular LH receptor on the Leydig cell.
What are the metabolites of testosterone metabolized by?
By cytochrome p450 enzymes.
What is testosterone? What is it converted into and why?
The major form of androgen in circulation. It can be converted to dihydrotestosterone (DHT). It is 10x more potent and is converted to this form to target peripheral tissues.
What converts testosterone into DHT?
5-alpha-reductase.
How are testosterone concentrations kept up in the testis? Is testosterone converted into DHT in the testes.
By androgen binding proteins synthesized by Sertoli cells in the seminiferous tubes. It is not converted in the testes (thus, the concentration must be kept up).
What do Sertoli cells do?
They stimulate spermatogenesis.
How are hormones transported to their target tissues?
After synthesis, they diffuse into the plasma. Then they bind to carrier proteins including sex-hormone binding globulin (SHBG) and Albumin. They can diffuse out of the blood and cross freely into target tissues.
What are androgen receptors? What happens when an androgen binds?
An intracellular receptor that trans-locates into the nucleus, binds DNA, and alters transcription upon androgen binding.
What disorder is caused by mutations in androgen receptors?
Androgen Insensitivity Syndrome (AIS). Genetically XY, but are female.
What are reasons to antagonize androgen action? (Anabolic steroids would make them worse.)
Treatment of: prostate cancer, male pattern baldness, benign prostatic hyperplasia.
What are two ways to antagonize androgen?
- Use GnRH agonists. 2. Use GnRH receptor antagonists.
How does using GnRH agonists antagonize androgen activity?
They suppress the hypothalamus-pituitary-gonadal axis, which decreases the production of FSH and LH, which shuts down testosterone production.
What can GnRH agonists treat? How is it administered?
Prostate cancer and some breast cancers. It is administered continuously.
How does using GnRH receptor antagonist reduce androgen activity?
They block the release of FSH and LH.
How do 5-alpha-reductase inhibitors work?
They block the conversion of testosterone into the more potent DHT.
What can 5a-reductase inhibitors do to prostate tissue?
Slows the growth of prostate tissue and cause cell death.
What is Finasteride?
It is a selective inhibitor of type 2 5a-reductase.
What can topical Finasteride (Propecia) treat?
Male-pattern baldness.
What can oral Finasteride treat? How much can it reduce prostate size in one year?
Benign prostatic hyperplasia (BPH). It can reduce prostate size by up to 25%.
What are the adverse effects of oral Finasteride?
Decreased libido and erectile dysfunction.
What is the mechanism of action for androgen receptor antagonists? (Not 5a reductase.)
Completely inhibits the binding of endogenous androgens to the androgen receptor.
What are 3 androgen receptor antagonists?
- Flutamide. 2. Enzalutamide. 3. Bicalutamide.
What are Androgen receptor antagonists used to treat?
Metastatic prostate cancer and benign prostatic hyperplasia.
What is CYP17?
An enzyme needed for the synthesis of androgens, including testosterone.
What is Abiraterone (Zytiga)? What can it be used for?
A CYP17 inhibitor. It can be used in the treatment of castration-resistant prostate cancer.
What are some medical uses of Anabolic steroids?
Hormone deficiency, treat muscle loss associated with trauma or disease. Gender re-assignment. Anti-aging (controversial) and male contraceptive (experimental).
What is hypogonadism? Can the treatment be administered orally?
Not enough male hormones are made. Can’t be administered orally because it is subject to first-pass metabolism by the liver.
What is Enanthate?
Inject-able testosterone.
What is Cypionate?
Inject-able testosterone.
How are Enanthate and Cypionate administered? What does it do?
Intramuscularly every 2-4 weeks. It increases plasma testosterone to the normal level.
What are the two types of pill contraceptives for women?
- Estrogen/progestin combinations. 2. Progestin only.
How do Estrogen-progestin combination contraceptives work?
Suppresses GnRH, LH, and FSH secretion and follicular development. It works to primarily prevent ovulation.
What are two progestin-only contraceptive drugs?
Norgestrel and Norethindrone.
How are progestin-only contraceptives thought to prevent ovulation?
They alter the frequency of GnRH pulsing and decrease anterior pituitary gland responsiveness to GnRH.
How effective are progestin-only drugs in preventing ovulation?
They prevent it 70-80% of the time.
How effective are progestin-only contraceptive drugs in preventing pregnancy?
96-98%.
Why are progestin-only contraceptive drugs ~97% effective instead of ~75%?
Due to secondary mechanisms: alterations in cervical mucus, endrometrial receptivity, and tubal peristalsis.
What is the goal of male contraceptives?
To suppress endogenous production of sperm reversibly.
What male contraceptives based on testosterone have been tried? How do they work?
Testosterone enanthate which significantly suppresses gonadotropin release, resulting in reduced levels of LH and FSH that can’t stimulate Sertoli cell function.
What 2 male contraceptives based on androgen and progestin have been tried?
- Testosterone enanthate and levonorgestrel. 2. Testosterone undecanoate and inject-able medroxyprogesterone acetate.
How effective were male contraceptives based on androgens and progestin at creating azoospermia in the population on average?
Only about 60% of men achieved the state.
Do Anabolic steroids increase strength and muscle mass without exercise?
Yes.
What are some side-effects of using anabolic steroids?
Hypertension, liver damage, male infertility, acne, mood/behavior changes, early death.
How can you detect steroid use?
By measuring the ratio of testosterone to its metabolites, such as epitestosterone. >4:1 is evidence of use.
