Week 4 Flashcards
What is the precursor of all glucocorticoids and mineralocorticoids?
Cholesterol
What enzyme is responsible for the conversion of testosterone into estradiol?
Aromatase
What are the three zones of synthesis in the adrenal medulla? What do they produce? Give an example?
Zona glomerulosa: produces mineralocorticoids (e.g. aldosterone)
Zona fasciculata: produces corticosteroids (e.g. cortisol)
Zona reticularis: produces androgens (e.g. testosterone)
Medulla: produces catecholamines (e.g. adrenaline)
Which is the only area in the adrenal gland that does NOT produce steroids? What does it produce?
Medulla: produces catecholamines (e.g. adrenaline)
Describe the process by which steroids work in the cell?
Steroids, unlike other drugs, do not bind to extracellular receptors. Steroids have the ability to enter the cell (being lipophilic), allowing them to bind to an intracellular receptor. Once the steroid-receptor complex is formed, the complex translocate into the nucleus. There, the complex will bind to a regulatory site, which will change the transcription sequence, and in turn, the translation of the proteins produced.
What are the 5 steroid receptors?
GR: Glucocorticoid receptor MR: Mineralocorticoid receptor ER: Estrogen receptor PR: Progesterone receptor AR: Androgen receptor
What is responsible for the production of estrogens before puberty? After puberty? During pregnancy? Describe the process of synthesis?
Before puberty, estrogens are synthesized from androgens by the enzyme aromatase in the adrenals. After puberty, most of the estrogens are produced by ovarian follicles stimulated by FSH and LH. Estrogens are also stimulated by placenta during pregnancy.
What is the most common type of estrogen?
17B-oestradiol
What mediates the activity of estrogen?
Cytoplasmic estrogen receptors
List some functions of estrogen?
- In the follicular phase of the menstrual cycle, it stimulates LH and FSH which then trigger ovulation.
- In the luteal phase of menstruation, alongside progesterone, estrogens inhibit the production of FSH and LH.
- They also allow for the development of secondary sexual characteristics (body shape, breast growth …)
- Promotes endometrial repair and fallopian motility
List a side effect of estrogen and describe the underlying cause of this side effect?
Estrogen is a steroid, but steroids are not 100% specific, so its action can cause some overlap with other steroids such as aldosterone which can cause aldosterone-like side effects such as fluid retention.
What are progestogens? What is the most common one?
Estrogen is a steroid, but steroids are not 100% specific, so its action can cause some overlap with other steroids such as aldosterone which can cause aldosterone-like side effects such as fluid retention.
What are some functions of progesterone?
- Inhibits LH and FSH during the luteal phase of the menstrual cycle
- Prepares endometrium for implantation
- Thickens cervical mucus
- Inhibits uterine contractility
- Promotes breast growth
- Suppresses lactation
What are the components of the combined oral contraceptive pill (COCP)?
Estrogen component: Ethinyloestradiol
Progestin component: Norgestrel
Describe the mechanisms of the combined oral contraceptive pill (COCP)?
Suppresses LH and FSH, slows follicular development
Prevents mid-cycle ovulatory surge of LH
Progestin causes asynchronous endometrial development and thickened cervical mucus
List a side effect of the combined oral contraceptive pill (COCP)?
Thromboembolic events
What is a key difference between latest generation and older progestin components in the combined oral contraceptive pill (COCP)?
Latest generation COCP have a progestin component that is much more specific to progesterone, and less androgenic which in turn causes less androgen-like side effects (e.g. hair growth)
What is progestin-only pill (POP)?
Progestin only contraception is a form a contraception that only utilizes progestin pharmacology as opposed to using a combined progestin-estrogen formulation like in the combined oral pill.
List different progestin-only contraception that exist and describe them? Talk about unwanted effects if applicable.
- Progestin-only pill (POP): pill taken continuously within a 3h window every day. Prevents ovulation in only 25-50% of women (prevents pregnancy through a different mechanism that preventing ovulation). The fact that it does not prevent ovulation gives rise to the rare (but possible case) of ectopic pregnancy.
- Intramuscular depot: Depot-Provera is an intramuscular injection that gradually leaches into the blood and prevents pregnancy over a span of 8-12 week. Prevents ovulation and therefore, no risk of ectopic pregnancy.
- Subcutaneous implant: Subcutaneous device that releases etonogestrel and works for a period of three years
- Intrauterine System (IUS): Levonorgestrel-releasing IUD that lasts 3-6 years
What is the active agent in the emergency contraceptive pill?
Levonorgestrel (progestin) or Ulipristal (Selective Progestin Receptor Modulator – SPRM)
List some non-contraceptive uses of estrogens and progestins?
Hormone replacement therapy: mainly estrogens for post-menopausal women
Dysmenorrhea: Progestins (and NSAIDS)
Abortion: mifepristone (SPRM)
List a common condition in which aromatase inhibitors are used and give the reasoning?
The growth of 60% of breast cancers is dependent on estrogen acting at cytoplasmic estrogen receptors. In post-menopausal women, most estrogen is derived from aromatase from androgens in the adrenal cortex. Aromatase inhibitors reduce estrogen synthesis and slow the growth of ER+ breast tumors.
What aromatase inhibitors are used in breast cancer? Lis the class of drugs and an example?
Reversible and non-steroidal: anastrozole
Irreversible and steroidal: exemestane
What is the biggest unwanted effect from the use of aromatase inhibitors? Why?
Osteoporosis, because they inhibit the production of estrogen.
What is the mechanism of action of SERM (selective estrogen receptor modulators)? What is its effect on ER+ breast tumor growth?
Block estrogen action at specific ER receptors. Reduces ER+ breast tumor growth in both pre- and post-menopausal women (blocks estrogen from all sources – ovarian, adrenal as opposed to aromatase inhibitors that only block estrogen production in the adrenal by blocking aromatase action).
Compare and contrast the unwanted effects of aromatase inhibitors and SERM and how it relates to their mechanism of action. Give examples.
Aromatase inhibitors prevent the production of estrogen in the adrenals. It prevents the growth of ER+ breast tumors in post-menopausal women whose only source of estrogen comes out of the adrenals. Blocking their only source of estrogen causes very low estrogen which increases risks of osteoporosis.
SERMs work by antagonizing the cytoplasmic estrogen receptors themselves. SERMs however have different actions at different ER subtypes. Drugs like tamoxifen antagonize ER-alpha (breast, hypothalamus, endometrium) receptors which inhibit ER+ breast tumor growth, while partially agonizing estrogen at ER-beta (bones, brain) receptors which gives a protection from osteoporosis.
Where in the body is testosterone produced in males?
Pre-pubertally: in the adrenals
Post-pubertally: Leydig cells in the testes (and some from the adrenals)
What are some physiological effects of androgens?
Development of primary and secondary sexual characteristics Spermatogenesis Increased bone and lean muscle mass Increased hemoglobin Aggression, hirsutism and libido
List a side effect of DHT (dihydro-testosterone)?
Promotes prostate growth
Male-pattern baldness
What are anabolic-androgenic steroids (AAS)? Give an example?
Testosterone derivatives. An example is stanozolol.
What is the physiological effect of anabolic androgenic steroids?
Increase lean muscle mass (With or without training)
Accelerate recovery from injury
List 5 side effects of anabolic androgenic steroid use?
Testicular shrinkage Hypertension Severe acne Heart attack Stroke
What are the two ways by which androgenic effects can be inhibited?
5a reductase inhibitors work as DHT (dihydro-testosterone) is produced from testosterone through 5a reductase, and therefore inhibiting that pathway also inhibits the production of DHT.
Directly inhibiting androgen receptors
Give an example of a 5a reductase inhibitor? Give two possible uses?
Finasteride. Could be used in benign prostatic hyperplasia, or male-pattern baldness
List an example of an androgen receptor antagonist and give two possible uses?
Flutamide and it is used mainly in prostate cancer, but could also be used for hirsutism or transgenderization.
