hormone signaling pathways

What two key characteristics must hormone receptors possess due to the low concentration of hormones in the body?

They must be specific and sensitive enough to detect their presence.

What two major body systems are linked by the hypothalamus and pituitary gland to maintain homeostasis?

The neuronal and endocrinological systems.

What lipid molecule, which is also an alcohol due to its -OH group, serves as a precursor for steroid hormones?

Cholesterol.

What property of cholesterol allows it to pass through the lipid bilayer and the blood-brain barrier?

It is both lipophilic (lipid) and hydrophilic (due to its -OH group).

Steroid hormones are grouped into two classes based on the receptors they bind to. What are these two classes?

Corticosteroids and sex steroids.

Which type of corticosteroids are typically made in the adrenal cortex?

Glucocorticoids and mineralocorticoids.

What are the three subtypes of sex steroids?

Androgens, oestrogens, and progestogens.

The _ domain of a nuclear receptor is involved in transcription regulation and is located at the N-terminus.

N-terminal

What is the function of the DNA binding domain (DBD) in a nuclear receptor?

It binds directly to specific sequences on the DNA.

The DNA binding domain of a nuclear receptor contains structures called '_', which are formed by cysteine residues coordinating with a zinc atom.

zinc fingers

How do zinc fingers in the DNA binding domain (DBD) interact with DNA?

They form a looped structure that can access the major groove of the DNA double helix.

What is the function of the flexible 'hinge region' in a nuclear receptor's structure?

It acts as a flexible connector between other domains.

Which domain of a nuclear receptor binds to the hormone or ligand?

The ligand binding domain (LBD).

What event triggers the conformational change in a nuclear receptor, releasing inhibitory proteins?

A ligand binding to the ligand binding domain (LBD).

After activation by a ligand, where does the nuclear receptor complex translocate to?

The nucleus.

What is the long-term cellular outcome after an active receptor-ligand complex binds to DNA?

Activation or repression of the transcription of nearby genes (primary response).

In the secondary response to hormone signaling, what two simultaneous actions do the primary-response proteins perform?

They shut off the primary-response genes while turning on secondary-response genes.

In its inactive state in the cytoplasm, the glucocorticoid receptor (GR) is bound to what kind of proteins?

HSP70 and FKBP52 chaperone proteins.

What is the primary medical use for drugs that target the glucocorticoid receptor (GR), such as dexamethasone?

They produce anti-inflammatory and immunosuppression effects.

What are two potential negative side effects of long-term use of glucocorticoid receptor agonists?

Bone loss and glucose dysregulation.

Cortisol is the final product of which physiological axis, which is activated in response to stress?

The hypothalamic-pituitary-adrenal (HPA) axis.

In the HPA axis, the hypothalamus releases CRH, which stimulates the pituitary to release what hormone?

Adrenocorticotropic hormone (ACTH).

What is the target organ of adrenocorticotropic hormone (ACTH) in the bloodstream?

The adrenal glands.

The arrival of ACTH at the adrenal glands stimulates the release of which hormone?

Cortisol (a glucocorticoid).

A condition characterized by too little cortisol due to damage to the adrenal glands is known as what?

Primary adrenal insufficiency.

In diagnosing adrenal issues, if a patient is given ACTH and their adrenal glands fail to produce cortisol, what does this indicate?

The adrenal glands are faulty.

What is the name of the life-threatening condition caused by a sudden lack of cortisol during severe stress?

Addisonian crisis.

What syndrome is caused by having too much cortisol in the body?

Cushing's syndrome.

Besides long-term steroid use, what is a common cause of Cushing's syndrome related to the pituitary gland?

An adenoma (tumor) growing in the pituitary gland, leading to increased ACTH production.

List three symptoms associated with Cushing's syndrome.

Weight gain, raised blood pressure, puffy face, and hair growth.

Type 1 diabetes is most often caused by the autoimmune destruction of what cell type?

beta cells (in the pancreas).

How is the insulin receptor initially synthesized and processed before it becomes a functional dimer?

It is transcribed as a monomer, cleaved, and then rejoined by disulfide bonds before dimerizing.

What is the immediate consequence of insulin binding to its receptor?

A conformational change brings the tyrosine kinase domains together, causing them to cross-phosphorylate (autophosphorylation).

After the insulin receptor is activated, what docking protein does it phosphorylate on tyrosine residues?

IRS1 (Insulin Receptor Substrate 1).

The phosphorylated tyrosine sites on IRS1 allow for the binding of what lipid kinase?

PI3K (Phosphoinositide 3-kinase).

What lipid second messenger does PI3K synthesize at the plasma membrane?

PtdIns(3,4,5)P3 (PIP3).

The second messenger PIP3 recruits _, which then directly phosphorylates the serine/threonine kinase Akt.

PDK (phosphoinositide-dependent kinase)

One major downstream effect of Akt activation is glucose uptake. How does Akt achieve this?

It triggers the translocation of GLUT4 vesicles to the cell membrane.

In terms of metabolism, activation of Akt promotes the synthesis of what two types of molecules?

Glycogen and fatty acids.

How does Akt promote cell growth and survival?

It activates mTORC1 and inhibits pro-apoptotic proteins like Bad and FoxO.

Akt phosphorylates TSC2, which permits the activation of _ and its downstream targets like S6K and SREBP1c.

mTORC1

Name one of the four key protein families or molecules that Akt can phosphorylate.

FOXO transcription factors, TSC2, GSK3-beta or TBC1D4.

What is the purpose of using long-acting 'background' insulin in Type 1 diabetes treatment?

To provide a constant baseline level of insulin replacement.

In Type 1 diabetes treatment, what is the purpose of administering fast-acting 'bolus' insulin?

To manage the glucose increase that occurs with meals.

What dangerous condition can result from an excess of insulin?

Hypoglycemia (too little blood sugar).

Why is hypoglycemia particularly dangerous for the brain?

The brain can only metabolize glucose for energy.

Type 2 diabetes can result from impaired insulin secretion, _, or both.

insulin resistance

List three common symptoms of Type 2 diabetes.

Thirst, frequent urination, tiredness, weight loss, slow-healing cuts, thrush, or blurred vision.

What are three long-term circulatory or tissue-damage complications associated with diabetes?

Circulatory problems, foot ulcers, and diabetic retinal damage/blindness.

What is one potential treatment for Type 2 diabetes that involves stimulating a specific receptor to increase insulin production and slow food absorption?

GLP1R (Glucagon-like peptide-1 receptor) stimulation.