Endocrinology Biology 640AC - Exam 1 Study Guide (Lecture Notes)

80 flashcards derived from lecture notes covering hormone definitions, signaling pathways, receptors, and steroid/thyroid hormone biology.

What is the definition of a hormone?

A substance secreted into the bloodstream, distributed to all parts of the body by the blood, and stimulates target cells.

What characteristic identifies a hormone target cell?

A target cell is any cell in the body that has a receptor for a given hormone.

What is the definition of a paracrine factor?

A paracrine factor is a growth factor secreted by a cell that is sensed by a neighboring cell that possesses a receptor for that growth factor.

What is the definition of an autocrine factor?

An autocrine factor is a growth factor secreted by a cell that also possesses a receptor for that growth factor, thereby stimulating itself.

Experimentally, which signaling is more difficult to distinguish: endocrine vs paracrine or autocrine vs paracrine?

Autocrine vs. paracrine signaling is more difficult to distinguish, therefore it is often lumped together.

Of the four types of organic molecules that comprise cells, which three are used as hormones?

Proteins, Lipids, and Nucleic Acids are used as hormones.

Name which type of the four organic molecule classes that is used as receptors for hormones.

All receptors are proteins.

What is a neurohormone?

A chemical messenger released by neurons into the bloodstream that acts like a hormone.

What is a neurotransmitter?

A chemical messenger released by neurons across a synaptic cleft to stimulate post-synaptic cell.

What hormone was discovered by Baylis and Starling?

Secretin.

Catecholamines and thyroxine are derived from what amino acid?

Tyrosine.

If yeast provide a model for single-celled eukaryotes and C. elegans a model for primitive multicellular organisms, what major difference between their genomes accommodates the need to coordinate cellular activities with organism function?

There was a great increase for signaling genes in C. elegans compared to yeast cells.

The classic endocrine glands and their secretions were discovered by what experimental approach?

The experimental approach included surgically removing the endocrine gland, observing the physiological effects, then replacement of the gland with extracts of the gland.

What major advance in measuring hormone concentrations was made possible by the studies of Yalow and Berson?

Radioimmunoassay which allowed for quantitative measure of the hormones in the blood.

In a competition assay, which values are in the usable range?

Values within experimental error, mean, and standard deviation, i.e., properly measured/diluted serum samples.

In dose-responses, what are the two major patterns observed when measuring response to increasing hormone concentration?

A sigmoidal curve and a biphasic curve.

What are the 4 major kinds of hormones derived from amino acids and proteins?

Amino acids, amino acid derivatives, peptides, and proteins.

Differentiate the three major endocrine systems found in the body.

1) Endocrine system: glands release hormones to target organs. 2) Neuroendocrine system: hypothalamus releases hormones to the anterior pituitary which releases trophic hormones to endocrine glands to release more hormones to reach the target organ. 3) Nonapeptide endocrine system: hypothalamus releases nonapeptides to the posterior pituitary for storage, then released to its target organ.

Name 3 major catecholamine hormones and their major endocrine sources.

Dopamine is released from the hypothalamus; Norepinephrine and Epinephrine are found in the adrenal gland.

Indolamine hormones are derived from what amino acid?

They are derived from the amino acid Tryptophan.

Name two major Indolamine hormones.

Serotonin and Melatonin.

Which of the two indolamine hormones is secreted by an endocrine gland and what is the name of that gland?

Melatonin is secreted by the pineal gland.

In the early days of peptide hormone studies, scientists speculated peptides were synthesized by a non-ribosomal mechanism similar to that used by bacteria. Was that speculation confirmed by subsequent research?

No—the peptides are synthesized on ribosomes.

In what cellular compartment are prehormones and preprohormones converted into hormones and prohormones, respectively?

Prehormones and preprohormones are converted in the rough endoplasmic reticulum.

In what cellular compartment are prohormones converted into hormones?

Prohormones are converted to hormones in secretory vesicles.

List the 3 common domains of membrane receptors?

The extracellular domain, the transmembrane domain, and the cytoplasmic domain.

In the enzyme-linked receptors, what are the three types of enzymes located in the cytoplasmic domains of each receptor?

Tyrosine Kinases, Serine/Threonine Kinases, and Guanylate cyclases.

In the G protein coupled receptors, name the domain which has seven secondary structure components?

The transmembrane domain consists of 7 helices.

What energy-bearing molecule becomes cAMP?

ATP becomes cAMP.

What enzyme converts the ATP precursor to cAMP?

Adenylyl cyclase converts the ATP precursor to cAMP.

Where in the cell is the cAMP-producing enzyme located?

cAMP is located in the plasma membrane of the cell.

What gives G protein-coupled receptors their name?

GPCRs are named because they bind to trimeric G-proteins.

When a G protein has GDP in its nucleotide binding site, is it active or inactive?

It is inactive if it has GDP in it’s binding site.

A G protein has GTP in its nucleotide binding site, is it active or inactive?

It is active if it has GTP in it’s binding site.

Briefly describe the series of activation steps in GPCR signaling pathway from its initiation with hormone binding, through cAMP, to activation of CREB.

The ligand binds GPCR, activating it. Activated GPCR activates G-aGDP(beta)(gamma). GDP dissociates from G(alpha)(beta)(gamma) complex. GTP binds G(alpha)(beta)(gamma). G(alpha)GTP(beta)(gamma) dissociates into G(alpha)-GTP and G(beta)(gamma). cAMP binds regulatory subunit of Protein Kinase A (PKA). PKA dissociates from PKA(cat) = active PKA. Active PKA phosphorylates cytoplasmic protein. Active PKA phosphorylates transcription factor CREB.

When an active GPCR activates a G protein what nucleotide is lost and which one is gained?

GDP is lost and GTP is gained.

When a G protein called Gs binds adenylyl cyclase, does cyclase activity increase or decrease?

Increase.

When a G protein called Gi binds adenylyl cyclase, does cyclase activity increase or decrease?

Decrease.

When a Ga protein hydrolyzes GTP to GDP, what happens to the activity of the G protein?

It inactivates itself.

Describe how the inactive signaling enzyme protein kinase A (PKA) is activated?

Two cAMPs bind each regulatory subunit. Two regulatory subunits are associated with two catalytic subunits. Then both catalytic subunits are now active.

Describe how the active signaling enzyme protein kinase A (PKA) is inactivated?

When cAMPs dissociate from the regulatory subunits, a regulatory subunit binds catalytic subunits and deactivates.

What is the active form of CREB?

The active form of CREB is phosphorylated CREB found in the nucleus.

What is the inactive form of CREB?

The inactive form of CREB is not phosphorylated and it is found in the cytoplasm.

What macromolecule does active CREB bind?

CREB binds to DNA at cAMP response elements.

Name the five major classes of steroid hormone.

Progestins, androgens, estrogens, glucocorticoids, and mineralocorticoids.

Given the steroid precursor structure below, number the carbon atoms.

Cannot determine without the structure image.

Given the structure shown below, circle the carbon atom that is modified by the enzyme 5a-reductase.

Cannot determine without the structure image.

Given the cholesterol structure below, name each of the rings.

Cannot determine without the structure image.

Name the steroid hormone that is precursor to androgens, glucocorticoids and mineralocorticoids.

Progesterone.

Name the steroid hormone that is precursor to estradiol.

Testosterone.

When steroids enter target cells, what protein do they bind to bring about changes in gene activity in the target cell nucleus?

Steroid hormone receptors, a type of nuclear receptor protein.

Name the two cellular compartments in which inactive steroid receptors may be found?

Cytoplasm and nucleus.

Name the cellular compartment in which active steroid receptors are found.

Nucleus.

When a steroid binds its receptor, what happens to the conformation of the receptor?

A conformational change switches the receptor from the inactive form to the active form.

When a steroid binds its receptor, what effect does the change induced have on chaperones bound to the receptor?

Chaperone dissociation from the receptor occurs.

What does chaperone dissociation expose on steroid receptors?

Zn finger for DNA-binding and the nuclear organization domains.

What is the source of the phosphate group when activated nuclear receptors are phosphorylated?

From ATP, via the action of protein kinases.

What does exposure of the nuclear localization signal near the DNA binding domain lead to in an activated receptor?

Transport of the activated receptor into the nucleus from the cytoplasm.

Nuclear receptors that reside in the nucleus in the inactive state do not bind DNA. What mechanism prevents DNA binding?

Chaperone binding prevents DNA binding.

Each steroid receptor has two Zn fingers. One binds DNA, what does the other bind?

The second Zn finger mediates dimerization by binding to the partner receptor.

Each steroid receptor has two Zn fingers. What do each of the Zn fingers bind?

First Zn finger binds DNA at the hormone response element; the second Zn finger mediates dimerization by binding another receptor.

A hormone response element (HRE) that binds androgen receptors is called a(n) ___ response element.

Androgen response element.

A hormone response element (HRE) that binds glucocorticoid receptors is called a(n) ___ response element.

Glucocorticoid response element.

The cartoon model of nuclear receptors shows the ligand-bound active receptor dimer bound to DNA, giving the impression it just sits there. In reality over a 3-hr period, how many times do estrogen receptors bind to the ERE?

On average, they bind about every 40 minutes so 4-5 times over a 3-hr period.

What kind of steroid receptor is hypothesized to mediate rapid, non-genomic functions of steroid hormones, such as progesterone activation of amphibian oocytes?

A membrane receptor.

What is testosterone converted to in some of its target cells before binding the androgen receptor?

Dihydrotestosterone (DHT).

When cortisol is converted to cortisone in some target cells possessing both mineral corticoid and glucocorticoid receptors what effect does this have on mineral corticoid receptors?

Cortisone only binds glucocorticoid receptors, so it won’t activate mineralocorticoid receptors.

Metabolism of steroids does two things, what are they?

Reduction and conjugation.

Thyroxine is derived from the amino acid residue ___.

Tyrosine.

While both catecholamines and thyroxine are both synthesized from tyrosine, how does thyroxine synthesis differ from catecholamine synthesis? (Not usually asked on tests)

Catecholamines are made from free tyrosine by hydroxylation and decarboxylation; thyroxine is synthesized from tyrosine residues in thyroglobulin via iodination and coupling.

What is the name of the serum protein that carries 90-99% of circulating T3 and T4?

Thyroxine-binding globulin (TBG).

Which form of thyroxine, T3 or T4, is considered to be the active form of the hormone?

T3.

The mechanism for steroid hormone entry into target cells is poorly understood. Thyroxine is also a hydrophobic molecule, but has a known transport protein called .

Monocarboxylate transporter 8 (MCT8).

Thyroid hormone receptors are nuclear receptors like steroid receptors. Most of the time the inactive receptors are found in what part of the cell?

Nucleus.

When bound to thyroid response elements (TRE), what is the stable, presumably functional dimer like? How does this differ from steroid receptor binding to SREs?

TREs form heterodimers; steroid receptors typically form homodimers when activated.

When T4 is deiodinated to T3 what is the effect on hormone activity?

Hormone activity increases.

When T4 is deiodinated to reverse T3, what happens to its activity via the classic thyroid receptor?

Its activity is lost; it does not bind to the classic thyroid receptor.

When T4 is deamidated and decarboxylated, what happens to its water solubility?

Water solubility increases, facilitating clearance.

What part of prostaglandin molecules distinguishes one type from another; ring substitution or chain substitution?

Ring substitution.

What kind of receptors do prostaglandins typically bind?

GPCRs (G protein-coupled receptors).

Name the steroid hormone that is precursor to androgens, glucocorticoids and mineralocorticoids.

Progesterone.

Name the steroid hormone that is precursor to estradiol.

Testosterone.

When steroids enter target cells, what protein do they bind to bring about changes in gene activity in the target cell nucleus?

Steroid hormone receptors, a type of nuclear receptor protein.

Name the two cellular compartments in which inactive steroid receptors may be found?

Cytoplasm and nucleus.

Name the cellular compartment in which active steroid receptors are found.

Nucleus.

When a steroid binds its receptor, what happens to the conformation of the receptor?

Conformational change switches the receptor from the inactive form to the active form.

When a steroid binds its receptor, what effect does the change induced have on chaperones bound to the receptor?

Chaperones dissociate from the receptor.

What does chaperone dissociation expose on steroid receptors?

Zn finger for DNA-binding and the nuclear organization domains.

What is the source of the phosphate group when activated nuclear receptors are phosphorylated?

From ATP, via the action of protein kinases.

What does exposure of the nuclear localization signal near the DNA binding domain lead to in an activated receptor?

Transport of the activated receptor into the nucleus from the cytoplasm.

Nuclear receptors that reside in the nucleus in the inactive state do not bind DNA. What mechanism prevents DNA binding?

Chaperone binding prevents DNA binding.

Each steroid receptor has two Zn fingers. One binds DNA, what does the other bind?

The second Zn finger mediates dimerization by binding to the partner receptor.

Each steroid receptor has two Zn fingers. What do each of the Zn fingers bind?

First Zn finger binds DNA at the hormone response element; the second Zn finger mediates dimerization by binding another receptor.

A hormone response element (HRE) that binds androgen receptors is called a(n) ___ response element.

Androgen response element.

A hormone response element (HRE) that binds glucocorticoid receptors is called a(n) ___ response element.

Glucocorticoid response element.

The cartoon model of nuclear receptors shows the ligand-bound active receptor dimer bound to DNA, giving the impression it just sits there. In reality over a 3-hr period, how many times do estrogen receptors bind to the ERE?

On average, they bind about every 40 minutes so 4-5 times over a 3-hr period.

What kind of steroid receptor is hypothesized to mediate rapid, non-genomic functions of steroid hormones, such as progesterone activation of amphibian oocytes?

A membrane receptor.

What is testosterone converted to in some of its target cells before binding the androgen receptor?

Dihydrotestosterone (DHT).

When cortisol is converted to cortisone in some target cells possessing both mineral corticoid and glucocorticoid receptors what effect does this have on mineral corticoid receptors?

Cortisone only binds glucocorticoid receptors, so it won’t activate mineralocorticoid receptors.

Metabolism of steroids does two things, what are they?

Reduction and conjugation.