Term
| What cells produce testosterone? |
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Definition
|
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Term
| What cells are responsible for spermatogenesis? |
|
Definition
| Sertoli cells in the seminiferous tubule |
|
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Term
| What hormones induce testosterone production in leydig cells? |
|
Definition
1. GnRH from hypothalamus
2. LH from anterior pituitary |
|
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Term
| What hormones induce spermatogenesis? |
|
Definition
1. GnRH from hypothalamus
2. FSH from anterior pituitary |
|
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Term
| What enzyme converts testosterone to estradiol? |
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Definition
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Term
| List androgenic effects of testosterone |
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Definition
a. Growth and development of internal and external genital glands.
b. Voice change (vocal cords) - increases in length and thickness.
c. Beard and body hairs growth/scalp hair thins and recedes.
d. Skin thickness increases/oily sebaceous gland secretion.
- causes acne
e. Central nervous system. |
|
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Term
| List anabolic effects of testosterone |
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Definition
a. Positive nitrogen balance
b. Protein synthesis
c. Muscle mass
d. Weight gain
e. Accelerated body growth
f. Bone growth
g. Closure of the epiphysis - estradiol effect – testosterone is converted to estrogen by
aromatase. |
|
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Term
| Can testosterone be administered orally? |
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Definition
| No, it is rapidly absorbed but metabolized in the liver |
|
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Term
| How is testosterone administered? |
|
Definition
Testosterone esters are injected i.m. and absorbed slowly for sustained activity.
- esters are metabolized to free testosterone |
|
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Term
| Describe testosterone distribution |
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Definition
| 98% of testosterone in the circulation is bound to a sex hormone - binding globulin. (testosterone - estrogen - binding globulin) and albumin. |
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Term
| Describe the mechanism of action of testosterone |
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Definition
Testosterone is converted to dihydrotestosterone in most target tissues; except the hypothalamus and pituitary
Dihydroxytestosterone can then act on a receptor and affect DNA transcription |
|
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Term
| Define Testosterone propionate (Testex) |
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Definition
|
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Term
| Define Methyltestosterone (Virilron) |
|
Definition
|
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Term
| Define Testosterone Transdermal (Testoderm) |
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Definition
| A testosterone path absorbed slowly |
|
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Term
| Define Oxandrolone (Oxandrin) |
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Definition
An anabolic steroid
Therefore, its ratio of anabolic/androgenic is higher than 2:1 (a natural androgen is 1:1) |
|
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Term
| What disorders would androgens be therapeutically administered for anabolic stimulation? |
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Definition
Used after chronic illness major injury (burns) or chemotherapy leading to tissue atrophy.
Steroids used to stimulate anabolism - enhance tissue repair and re-growth.
(Of course, there are also illegal athletic uses) |
|
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Term
| What is the difference between an anabolic and androgenic steroid? |
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Definition
The ratio of anabolic/androgenic effect
An anabolic steroid ratio is higher than 2:1 (a natural androgen is 1:1) |
|
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Term
| List major side effects of androgens |
|
Definition
1. Jaundice
2. Edema
3. Testicular atrophy (due to negative feedback, low GnRH)
4. Prostate cancer
5. Feminization in men, masculization in women |
|
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Term
| Why do androgens cause jaundice? |
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Definition
| Hepatic cholistasis and accumulation of bile (over months or years of therapy) |
|
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Term
| Why do androgens cause edema? |
|
Definition
Testosterone and aldosterone have similar structure, causing H20 and Na retention
(Especially for anabolic steroids, not so much for testosterone) |
|
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Term
| Why would androgen therapy cause male feminization? |
|
Definition
| Testosterone is converted by aromatase to estradiol |
|
|
Term
|
Definition
Breast enlargement in men
Observed in 80% of strength athletes |
|
|
Term
| Describe the mechanism of action of Gonadotropin-releasing hormone for therapy (Leuprolide) |
|
Definition
Inhibits LH secretion (as a “superactive analog”) which leads to a
reduction in testosterone production and release
Prostatic cancer is a primary application. |
|
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Term
| Define and describe Finasteride (Proscar) |
|
Definition
Inhibition of 5α- reductase greatly reduces the conversion of
inactive testosterone to the activated metabolite – dihydrotestosterone
(to treat prostatic hypertrophy and male pattern baldness) |
|
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Term
| How does Spironolactone treat hirsutism? |
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Definition
| It is a weak androgen receptor antagonist since its structure is similar to testosterone |
|
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Term
| Define and describe Flutamide (Eulexin) |
|
Definition
A non-steroidal androgen receptor; inhibits translocation of activated androgen receptor to nucleus
Most effective when used with Leuprolide |
|
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Term
| List the pathway of biosyntheis of estrogen |
|
Definition
| Acetate -> cholesterol -> progerterone -> testosterone -> (aromatase) estradiol |
|
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Term
| Describe the hormonal regulation of ovarian steroids |
|
Definition
| Hypothalamus releases GnRH in 24-hr pulses, anterior pituitary releases FSH and LH, ovaries release estrogen and progesterone |
|
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Term
| What are the three stages of the menstrual cycle? |
|
Definition
| Menses, follicular, luteal |
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Term
| What hormone increases during pregnancy within the first 60 days? |
|
Definition
|
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Term
| What maintains the corteus leuteum to produce estrogen and progesterone when HCG secretion goes down after day 60? |
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Definition
|
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Term
| List biological activity of estrogen |
|
Definition
| Female secondary sexual characteristics. Protective effect on bone and CV system |
|
|
Term
| What is the role of progesterone? |
|
Definition
Actions are secondary to estrogen.
- necessary for complete sexual development, menstrual regulation and
pregnancy. |
|
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Term
| What is the role of Selective Estrogen Receptor Modulators (SERM)? |
|
Definition
| Act at the ER and produce modulate estradiol activity. |
|
|
Term
| What are the two estrogen receptors? |
|
Definition
ER-α found in reproductive tissue
ER-ß found in CV and bone tissue |
|
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Term
| Describe ADME of estrogen |
|
Definition
a. Readily absorbed.
b. First pass metabolism in liver (if non-synthetic)
c. Synthetic estrogens resistant to metabolism - effective orally
d. Bound to sex hormone-binding globulin (SHBG) and albumin |
|
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Term
|
Definition
Natural conjugated estrogen
Sulfated esters of estrone |
|
|
Term
| Define Estinyl (ethinyl estradiol) |
|
Definition
|
|
Term
| Define Diethylstilbesterol (Stilphostrol) |
|
Definition
|
|
Term
| List side effects of estrogen |
|
Definition
a. Nausea - most common
b. Other; fluid retention, CV (stroke, thromboembolism), chloasma (skin darkening), breast cancer |
|
|
Term
|
Definition
Drugs are also referred to as SERM (selective ER modifiers ) –
bind to ER α or β.
Produce differing degrees of estradiol Agonist/antagonist activity |
|
|
Term
| Define and describe Tamoxifen (Nolvadex) |
|
Definition
- used for breast cancer
- produces mixed agonist/antagonist activity |
|
|
Term
| Define and describe Raloxifene (Evista) |
|
Definition
- Selective agonist for the ER-β / ER-α antagonist
- used to treat or prevent postmenopausal osteoporosis. |
|
|
Term
| Define and describe Anastrozole (Arimidex) |
|
Definition
- Inhibits aromatase to abolish adrenal-generated androstenedione ---> estradiol in peripheral tissues (e.g. fat muscle).
- Used in advanced breast cancer and cancer metastasis following Tamoxifen. |
|
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Term
| Define and describe Progesterone acetate (Cyclin) |
|
Definition
A progestin
- i.m. administration – poor GI absorption.
- Available as a gel for local intra-vaginal therapy. |
|
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Term
| Define and describe Norethindrone (Norlutin) |
|
Definition
| A synthetic progestin with good oral activity- used in oral contraceptives |
|
|
Term
| Define RU-486 (Mifepristone) |
|
Definition
11β- substituted derivative of norethindrone
Acts as a competitive receptor antagonist
Used to produce a medical abortion – prevents implantation of fertilized ovum.
FDA approved in 2000. |
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