Lecture 60 Flashcards
What is a hormone?
1) A hormone is a chemical messenger that is synthesized and secreted by specialized cells in response to an external signal
2) For the most part, hormones are synthesized in one tissue and effect another
What are 4 major steroid hormones?
1) Cortisol
2) Aldosterone
3) Estradiol
4) Testosterone
What are characteristics of cortisol?
1) Synthesized in the adrenal glands
2) 21 Carbons
3) Affects the liver
4) Increases gluconeogenesis (gluconeogenic enzymes)
What are characteristics of aldosterone?
1) Synthesized in adrenal glands
2) 21 Carbons
3) Affects the kidney
4) Increases Na+ reabsorption & increases K+ excretion
What are characteristics of estradiol?
1) Synthesized in ovary (also small amounts in adrenal glands)
2) 18 Carbons
3) Affects the Uterus
4) Increases uterine mass
What are characteristics of testosterone?
1) Synthesized in the testes (small amounts in the adrenal glands)
2) 19 Carbons
3) Affects muscle
4) Increases muscle mass
What is the structure of a general steroid hormone?
1) 4 ring structure, with each ring labeled A, B, C, or D
2) Carbons 20 and 21 are branched off of carbon 17
What is the structure of cortisol?
1) 21 hydroxylase
2) 17 hydroxylase
3) 11 hydroxylase
What are the hydroxyl groups in cortisol important for its function?
Hydroxyl groups are important for the gluconeogenic activity of cortisol
What is the structure of aldosterone?
1) 21 hydroxylase
2) 18 hydroxylase
3) 11 hydroxylase
What is the same in the structures of estradiol & testosterone?
17 hydroxylase
What is different in the structures of estradiol & testosterone?
1) Estradiol contains a phenolic A ring
2) Testosterone contains an A ring with a double bond between carbons 4 & 5
Describe the pathway by which cortisol is produced
1) Stress induces the hypothalamus to produces corticotropic releasing factor (CRF)
2) CRF induces the pituitary gland to release Adrenocorticotropic Hormone (ACTH)
3) ACTH induces the adrenal glands to produce cortisol
How is the cortisol production pathway regulated?
Cortisol autoregulates its own production pathway when it is present in high levels by inhibiting corticotropic releasing factor (CRF) & Adrenocorticotropic hormone (ACTH)
What is the same between ACTH and Melanocyte Stimulating Hormone (MSH)?
Both hormones contain an identical first 13 amino acids
What occurs in adrenal insufficiency?
Elevated levels of ACTH cause binding to MSH receptor and causes skin darkening
What is Addison’s disease?
1) Addison’s disease is a disorder that occurs when your body produces insufficient amounts of certain hormones produced by your adrenal glands
2) In Addison’s disease, your adrenal glands produce too little cortisol and often insufficient levels of aldosterone as well
3) It is usually first observed in the oral cavity
What is the function of desmolase?
1) A desmolase enzyme is one that catalyzes the formation or destruction of carbon-carbon bonds within a molecule
2) Splits side chains of cholesterol
3) Allows you to add hydroxyl groups
4) 21, 17, 11, 18 hydroxylase
What are three characteristics of steroids?
1) Derived from cholesterol
2) Similar in strucure
3) Effective at very small concentrations (10^-8M)
What are two functions of ACTH?
1) Allows cholesterol to be released from adrenal storage
2) Activates desmolase
How are water insoluble cholesterols transported through the blood?
1) Steroid hormones bound by certain plasma proteins
2) Cortisol is bound by CBG (Cortisol binding globulin)
3) Estradiol + Testosterone are bound by sex hormone binding globulin (SHBG)
4) Aldosterone is bound by Aldosterone Binding Globulin (ABG)
What mediates the specificity of steroid hormones?
1) Specificity is due to the presence of high affinity intracellular receptors that are specific for the specific hormone
2) Hormones travel to all cells, but only activate those with these intracellular receptors
3) Activated receptor is transported to the nucleus to affect transcription
4) Hormones contain DNA binding domains with zinc fingers that bind to hormone response elements
How can cofactors assist hormone receptors?
1) They can either be coactivators or corepressors
2) A number of coactivators are histone acetyl transferases
a) Histone acetyl transferases cause histone acetylation so that histones bind less tightly to DNA, allowing looser DNA & more transcription (affect RNA Pol 2)
How was steroid hormone action mediated in breast cancer trials?
1) Rats were given breast cancer with the use of DMBA & removal of ovaries (ovariectimized)
2) Only worked in 30% of women
3) Women respond to endocrine ablative therapy if they have breast cancer and are estrogen receptor positive (ER+)
4) Tamoxifen is an antiestrogen (blocks estrogen receptors)
5) Can also use aromitase inhibitor to prevent formation of estradiol from testosterone?
