Myers Flashcards

What three biological processes do Androgens (Testes) regulate?

What three biological processes do Estrogens (Ovary, Placenta) regulate?

What two biological processes does Progesterone (ovary and placenta) regulate?

What four biological processes do Glucocorticoids (cortisol, adrenal cortex) regulate?

What two biological processes do Mineralocorticoids (aldosterone, adrenal cortex) regulate?

All steroid hormones are derived from what molecule?

Where are cholesterol esters stored? How are they taken up by steroidogenic tissues? How are they liberated?

What is a secondary source of cholesterol?

Where does Esterification occur on the cholesterol ring?

What does Esterification do?

What is the first rate limiting step in steroid hormone formation? What protein allows this step to happen?

What is the first rate limiting ENZYMATIC step of steroid hormone formation? What mediates this step? What is the resulting steroid precursor?

Unlike cholesterol, Pregnenolone has greater _________ and can permeate the IMM and OMM and diffuse throughout the cell

Is progesterone a biologically active steroid?

Post-ovulation, what is the major female circulating hormone?

Are 17-alpha hydroxypregnenolone and 17-alpha hydroxyprogesterone biologically active?

Biologically, what is the most active glucocorticoid in humans?

What is the target organ of glucocorticoids? What do they regulate?

All members of the CYP_C11 family are _________ enzymes.

The conversion of 17-alpha hydroxypregnenolone to DHEA via P450_C17 lyase activity is dependent on what two things?

What is the main male androgen?

When do DHEA levels begin to drop in males?

What is the most biologically active Estrogen?

What are the three Mineralocorticoids? Are they weak or strong biologically?

What are the three Glucocorticoids? Classify them as biologically weak or strong?

What are the five Androgens? Classify them as weak or strong.

What is the most potent of all androgens?

What are the three Estrogens? Classify them as biologically weak or strong.

5-alpha dihydrotestosterone (5-alpha DHT) plays a critical role developmentally in males. What happens to males born with a defect or deficiency in this androgen?

How can cortisol be converted to coritsone? What does this do?

How can Progesterone be converted to 20-alpha dihydroprogesterone? How can it be converted to 5-alpha dihydroprogesterone? What do these forms do, and where are they important?

In circulation, steroid hormones are largely bound (95-99%) by binding globulins. What is the specific binding globulin for Estradiol and Testosterone?

In circulation, steroid hormones are largely bound (95-99%) by binding globulins. What is the specific binding globulin for Progesterone, Gluco- & Mineralocorticoids?

In circulation, steroid hormones are largely bound (95-99%) by binding globulins. What binds all steroids, but weaker than specific globulins?

Which fraction (free or unfree) of the steroid hormone is biologically active?

What is the purpose of the bound steroids?

What are the two primary means of steroid clearance?

What is the primary enzyme involved in steroid clearance?

How are steroids metabolized in the liver?

How are steroids metabolized by the kidney?

What are the five major defects associated with Steroidogenesis?

What is the most common major defect in Steroidogenesis?

This is an AR defect that presents in newborns. There is an inability to synthesize 11-deoxy-cortisol and 11-deoxy-corticosterone, which results in an inability to produce what two major steroid hormones? The result of this is that Progesterone and 17-alpha hydroxyprogesterone are diverted to androgen synthesis. This leads to masculinization of the female, as well as to salt wasting. What is the name of the disease, and what enzyme is defected?

In this defect in Steroidogenesis, there is an inability to produce cortisol and aldosterone. 11-deoxycortisol and 11-deoxycorticosterone are the major steroids produced in the adrenal gland. These are weak glucocorticoids and mineralocorticoids, but feedback is broken on regulation of their synthesis so they increase in concentration, giving them a greater effect. This can push toward hypertension. What is the defect involved?

In this AR defect in Steroidogenesis, there is an inability to produce 17-hydroxyprogesterone or 17-hydroxypregnenolone. Therefore, cannot make androgens OR cortisol. Can synthesize aldosterone and corticosterone though. Results in a cortisol deficiency and no androgens. What is the defect?

In this defect in Steroidogenesis, there is an inability to synthesize steroids. What is it?

In this defect in Steroidogenesis, there is an inability to synthesize 5-alpha DHT. This results in a failure of testicular descent and masculinization of male genitalia.

What is the primary source for steroid formation?

To be steroidogenic, a molecule must express what two things?

What is the function of metabolism in steroidogenesis?

Steroid hormones mediate their cellular signaling via ligand activated transcription factors known as what?

The Nuclear Receptor Superfamily are members of what family of transcription factors?

What is the major function of the Nuclear Receptor Superfamily?

What modulates the transcription function of a receptor?

Which domain of the nuclear receptor is highly variable and receptor specific, and associates with co-repressors or co-activators, thereby regulating transcription? Co-repressors and co-activators are ezymes that modify histone structure through acetylation or deacytlation.

Which domain of the nuclear receptor is highly conserved, and has two zinc finger binding regions: has specific interaction with DNA recognition sequences (cis elements). There is a weak dimerization sequence: the nuclear receptors function as homo/heterodimers

Which region of the nuclear receptor has a nuclear localization sequence? This signals transport of receptor to nucleus either upon synthesis or signals transport of the receptor to nucleus upon steroid hormone binding.

Which domain within the nuclear receptor provides structure allowing each receptor to recognize and bind to its specific ligand with high affinity? This is a second strong dimerization domain. The Activating Factor (AF-2) domain within this domain binds co-activators or co-repressors and regulates transcription

Which domain within the Ligand Binding Domain associates with co-repressors or co-activators after hormone induced conformational change?

This nuclear receptor type is the classic steroid hormone receptor family (ER, AR, PR, GR, MR). Its ligands easily penetrate through the lipid bilayer. These receptors are located in the cytoplasm in the unliganded state. They are associated with heat shock proteins and other chaperone proteins to stabilize the receptor structure and keep it in the cytoplasm.

What is the purpose of the heat shock and other chaperone proteins associated with the inactive (unliganded state) of Type I Nuclear Receptors?

With Type I Nuclear Receptors, what 4 things happen upon Ligand Binding?

These are DNA sequences that serve as binding sites for the nuclear receptor in the regulatory region (5'-flanking to the transcription start site) of the target gene.
These are variations of a 'core' steroid response element and are typically gene specific
They function as an 'inverted palindrome'

Upon DNA binding, nuclear receptors recruit ___________, which increase the transcription rate of the target gene.

What do Histone Acetyltransferases (HATs) do?

What is the typical Histone Acetyltransferase (HAT) for nuclear receptors?

HATs (typically SRC 1, 2, 3) _________ Arg/Lys residues in Histone 3 and 4. This reduces the ________ of the histone and thus the protein: DNA interaction between the nucleosome and DNA. This then facilitates ___________ formation (loose chromatin structure). There is then recruitment of _______ __________ ___. Transcription initiation and an increased rate of transcription occurs, which increases ________, and _______ _______. What is the final result?

Upon DNA binding, nuclear receptors recruit ____________, which decrease the transcription rate of target genes that are repressed by that hormone.

What are the major Co-Repressors?

Histone Deactylases (HDACs) _________ the Arg/Lys residues on Histone 3 and 4. This increases the ________ and thus increases protein: DNA interaction. This then condenses the chromatin structure, resulting in _____________ formation. _____ _________ ____ dissociates and cannot be recruited to target genes, resulting in decreased transcription. ________ and ________ levels decrease. What is the end result?

This type of receptors have ligands that can easily penetrate through the lipid bilayer. They are located in the nucleus, and are DNA bound in the unliganded state. A conformational change results from ligand binding.
Common types are retinoic acid receptors, vitamin D receptors, thyroid hormone receptors, and PPARs.

Type I Nuclear Receptors are DNA-bound in the ________ state, whereas Type II Nuclear Receptors are DNA bound in the _________ state.

In Type II Nuclear Receptors, the cis elements serve as an '________ _________' usually with a variable N spacer sequence of 0-5 nucleotides.

The degree of transcriptional modification by a nuclear receptor is proportional to the __________ of that given hormone. What is this known as?

These are invaluable tools for treating endocrine diseases, such as cancer.

This invaluable tool for preventing endocrine diseases blocks the ability of the receptor to bind ligand, and therefore the receptor remains in a pre-ligand binding state for that class. What is the tool, and what is an example of it?

This invaluable tool for preventing endocrine diseases changes the conformation of the receptor such that the receptor switches from binding co-activators to co-repressors and actively suppresses target genes. What is the tool, and what is an example of it?

This invaluable tool for preventing endocrine diseases blocks the function of the receptor on some but not all target genes. It is cell type dependent. What is it, and what is an example of it?

What are the two most common heat shock proteins and chaperone proteins associated with Type I Nuclear Receptors?

In the Type I Nuclear Receptors what specifically dictates whether co-activators or co-repressors are recruited?

The Cis elements associated with the Type I Nuclear Receptors are palindromic, and are separated by what? They are not always perfectly palindromic, but can vary a little (70-80% conserved). What does the variations allow?

Within the Type II Nuclear Receptors, this is a member of the retinoic acid family, and can form a heterodimer partner with all type II receptors.

In the Type II Nuclear Receptors, what dictates whether co-activators or co-repressors are recruited?

What are the 5 Type I receptor family members, and what specific ligand is associated with each?

What are the four Type II receptor family members, and what specific ligand is associated with each?