NBP101: Endocrine System MEEEE

Furlow Study Guide SP2025

What are the different kinds of cell-to-cell signaling?

• Endocrine: hormones secreted into blood, act on distant targets

• Paracrine: signals affect nearby cells

• Neurotransmitters: secreted by neurons at synapses to target cells

What is the difference between a hormone and a neurotransmitter (or paracrine signal)?

• Hormone: Travels through the bloodstream, affects distant cells

• Neurotransmitter: Acts across a synapse on a nearby neuron or target

• Paracrine signal: Diffuses locally to affect nearby cells

How do neural and endocrine signaling compare and contrast?

• Neural signaling: Fast, short-acting, specific target via synapse

• Endocrine signaling: Slower, longer-lasting, broad targets via blood

What are examples of hormone-secreting organs?

• Dedicated glands: Pituitary, thyroid, adrenal glands

• Mixed-function organs: Brain, liver

• Borderline organs: Pancreas, gonads (they contain discrete hormone-secreting structures)

What are the general physiological functions controlled by the endocrine system?

Growth, metabolism, development, reproduction, homeostasis, and response to stress

What is the difference between hydrophilic and lipophilic hormones?

• Hydrophilic: Water-soluble, cannot cross membranes easily, bind to surface receptors

• Lipophilic: Fat-soluble, cross membranes, bind to intracellular receptors

What are amino acid derivative hormones, and what are some examples?

Tyrosine: Epinephrine, Norepinephrine, Dopamine

Tryptophan: Melatonin

What are peptide hormones, and what are some examples?

• The largest class of hormones; all are hydrophilic

• Examples:

  • Posterior & anterior pituitary hormones

  • Hypothalamic releasing/inhibiting hormones (except dopamine)

  • Insulin, glucagon, incretins (e.g., GLP-1), IGF-1, angiotensin II

How are peptide hormones synthesized and processed?

• Made by transcription and translation of hormone-encoding genes

• Processed in the Golgi apparatus

• Packaged in secretory vesicles, stored, and secreted when needed

What are thyroid hormones, and how do they behave?

• T3 (Triiodothyronine) and T4 (Thyroxine)

• Derived from tyrosines on thyroglobulin with 3 or 4 iodines

• Lipophilic in nature, act like steroids

• T3 is the most active form

What are steroid hormones and how are they made?

• Derived from cholesterol via steroidogenic enzymes

• Lipophilic and slightly more water-soluble than cholesterol

• Made in the adrenal cortex and gonads

What determines the specific steroid hormone produced in a cell?

The type and activity of the steroidogenic enzymes present, made only when needed

What receptors do various steroid hormones activate? (lipophilic hormones)

• Cholesterol Derivatives:

• Estrogens (e.g., estradiol) → estrogen receptor

• Androgens (e.g., testosterone) → androgen receptor

• Glucocorticoids (e.g., cortisol) → glucocorticoid receptor

• Mineralocorticoids (e.g., aldosterone) → mineralocorticoid receptor

• Progesterone → progesterone receptor

How are hydrophilic and lipophilic hormones stored and released?

• Hydrophilic hormones: Stored in secretory vesicles, released when needed

• Lipophilic hormones: Not stored—they diffuse out of cells as soon as they are made

What is an example of a hormone that follows a circadian rhythm and what is the significance?

• Cortisol follows a circadian rhythm

• This is considered a feed-forward mechanism, where secretion anticipates daily needs (e.g., waking up)

How are hydrophilic and lipophilic hormones transported in the bloodstream?

• Hydrophilic hormones: Circulate freely in the blood

• Lipophilic hormones: Require carrier proteins for transport

  • Carrier levels affect how much hormone is available to cells or lost in urine

How are peptide (hydrophilic) hormones inactivated (less active)?

Cleaved by general proteases in circulation at multiple amino acid bonds

How are lipophilic hormones inactivated and cleared?

Modified by the liver to become more water-soluble, allowing for renal excretion in urine

Can hormones be activated outside of the gland that secretes them? Give examples.

Yes. Examples include:

• Renin-angiotensin system

• Deiodinases that convert T4 to T3 for thyroid hormone activation

• 5α-reductase converting testosterone to DHT (covered in reproduction lectures)

What types of receptors do hydrophilic versus lipophilic hormones act through?

• Hydrophilic hormones: Bind to membrane receptors (e.g., G protein-coupled receptors)

• Lipophilic hormones: Bind to intracellular or nuclear receptors

What is an example of a membrane receptor signaling pathway for hydrophilic hormones?

1. Epinephrine binds to receptor

2. G protein-coupled receptor

3. Activation of adenylate cyclase

4. Production of cAMP

5. Activation of protein kinase A (PKA)

   Leads to increased liver glycogenolysis

How do lipophilic hormones signal through nuclear receptors?

• Bind to hormone response elements on DNA to regulate transcription

• Examples:

  • Estrogen in uterus/mammary gland

  • Thyroid hormone in brain

• Effects are slower than membrane receptor pathways but longer-lasting

What is the role of negative feedback in hormone regulation?

Negative feedback helps maintain hormone levels within a normal range by reducing secretion when hormone levels are sufficient. Many hormone systems rely on this mechanism.

What do the terms permissiveness, synergism, and antagonism mean in hormone interactions?

• Permissiveness: One hormone enables another to exert its full effect

• Synergism: Two hormones produce a greater effect together than individually

• Antagonism: One hormone opposes the action of another

What general factors regulate endocrine function?

Receptor number or activity, metabolic activation or inactivation of hormones, and hormone transport mechanisms

What are common causes of endocrine disorders?

• Excess hormone activity (e.g., hypersecretion)

• Insufficient hormone activity (e.g., hyposecretion)

• Abnormal receptor function or signaling

• Impaired hormone transport or metabolism

What is the primary goal of glucose homeostasis?

To maintain blood glucose levels within a narrow range to support energy needs, especially for the brain, while avoiding the harmful effects of hyper- or hypoglycemia.

What are the major circulating forms of nutrients and their storage forms? (carbs/fats/proteins)

• Carbohydrates: circulate as glucose, stored as glycogen in liver and muscle

• Fats: circulate as fatty acids, stored as triglycerides in adipose tissue

• Proteins: circulate as amino acids, stored as muscle protein

What fuel can the brain use, and can it store fuel?

The brain can use only glucose (or ketone bodies from the liver) and cannot store glucose.

What do anabolic and catabolic reactions do?

• Anabolic: build molecules and store energy (e.g., glycogenesis, protein synthesis)

• Catabolic: break down molecules to release energy (e.g., glycogenolysis, proteolysis)

What is the absorptive state and what reactions dominate during it?

The period after eating when nutrients are being absorbed. Dominated by anabolic reactions: glycogenesis, lipogenesis, and protein synthesis.

What is the postabsorptive state and what reactions dominate during it?

The period between meals or fasting. Dominated by catabolic reactions: glycogenolysis, gluconeogenesis, lipolysis, and proteolysis.

What are the consequences of hyperglycemia?

High blood glucose can lead to glucosuria, osmotic diuresis, dehydration, and if prolonged, damage to organs.

What is osmotic diuresis?

Increased urination due to high glucose levels in the kidney tubules, which pulls water into the urine by osmosis.

Which cells take up most glucose in the absorptive state, and what do they do with it?

Resting muscle and fat cells (adipocytes) using insulin-stimulated GLUT4 transporters. They store excess glucose as glycogen or fat.

What are the endocrine and exocrine functions of the pancreas?

• Endocrine: hormones secreted into the blood (insulin from beta cells, glucagon from alpha cells)

• Exocrine: digestive enzymes secreted into the gut lumen (considered "outside the body")

What stimulates insulin secretion?

High blood glucose (main), elevated blood amino acids, incretins like GLP-1, and parasympathetic nervous system activity when food enters the digestive tract.

What inhibits insulin secretion?

Low blood glucose, sympathetic nervous system activation, and epinephrine.

What is the main function of insulin in the absorptive state?

To promote nutrient storage by increasing glucose uptake, glycogen synthesis, fat synthesis, and protein synthesis, while inhibiting breakdown pathways.

What is the role of GLUT4 in insulin action?

insulin-sensitive glucose transporter found in adipocytes and resting skeletal muscle, which increases glucose uptake when insulin is present.

Does the brain need insulin for glucose uptake?

No. The brain takes up glucose independently of insulin.

What about the liver and contracting skeletal muscle—do they need insulin for glucose uptake?

No. The liver uses GLUT2 (always present) and can take up glucose without insulin; contracting skeletal muscle can also take up glucose independently of insulin.

What are insulin's effects on carbohydrate metabolism?

(glycogenesis, glycogenolysis, gluconeogenesis, blood glucose levels)

Increases glycogenesis, decreases glycogenolysis and gluconeogenesis, thereby lowering blood glucose levels.

What are insulin’s effects on fat and protein metabolism?

Promotes fat storage (lipogenesis) and protein synthesis; inhibits lipolysis and proteolysis.

What is the primary role of glucagon in the body?

Glucagon acts as a postabsorptive state hormone that increases blood glucose levels by promoting catabolic processes such as glycogenolysis and gluconeogenesis.

Where is glucagon secreted from?

alpha cells in the islets of Langerhans of the pancreas.

What are the effects of glucagon on carbohydrate metabolism?

Increases glycogenolysis and gluconeogenesis in the liver, leading to an increase in plasma glucose levels.

What are the effects of glucagon on fat metabolism?

Stimulates lipolysis, releasing fatty acids from adipose tissue. These fatty acids can be used by the liver to produce ketoacids (limited ketogenesis), which are alternative energy sources.

What are glucagon’s effects on protein metabolism?

no significant direct effect

What is the major stimulus for glucagon secretion?

Low blood glucose levels.

What are other stimuli for glucagon secretion besides low glucose?

Low blood fatty acid levels and high blood amino acid levels (especially after a high-protein, low-carb meal) to protect against hypoglycemia caused by insulin release.

What inhibits glucagon secretion?

High blood glucose levels.

Does glucagon have a direct effect on the brain?

No

How does glucagon indirectly support the brain's energy needs?

By stimulating peripheral tissues to use alternative fuels (like fatty acids and ketones), helps preserve glucose

Does glucagon have a direct effect on skeletal muscle?

no

What changes occur in skeletal muscle in the absence of insulin during the postabsorptive state?

Increased glycogen breakdown, decreased glucose uptake, and decreased proteolysis due to low insulin levels.

What are the two main types of diabetes mellitus?

Type I diabetes and Type II diabetes.

What are general features of Type I diabetes mellitus?

It is typically caused by autoimmune destruction of pancreatic beta cells, leading to an absolute insulin deficiency.

What are general features of Type II diabetes mellitus?

Characterized by insulin resistance and a relative insulin deficiency; most common form of diabetes.

Which type of diabetes is more common?

Type II diabetes is more common than Type I.

What is the significance of HbA1c measurement?

It reflects average blood glucose over the past 2–3 months and is used to diagnose and monitor diabetes.

What are general treatments and lifestyle changes for Type I and Type II diabetes?

• Type I: Insulin injections are necessary

• Type II: Lifestyle changes (diet, exercise), oral medications, and sometimes insulin if blood glucose cannot be controlled otherwise

What happens to carbohydrate metabolism in untreated diabetes mellitus?

• Increased liver glucose output

• Decreased glucose uptake by cells

• Increased gluconeogenesis

• Hyperglycemia

• Glucosuria when renal threshold is exceeded

• Osmotic diuresis and dehydration

• Hunger (polyphagia) and excessive thirst (polydipsia)

What is the cause and consequence of glucosuria in diabetes?

When blood glucose exceeds the renal reabsorption threshold, glucose appears in urine (glucosuria), leading to osmotic diuresis.

What is the consequence of osmotic diuresis?

Causes dehydration, which can impair circulation and neural function if untreated.

What happens to fat metabolism in untreated diabetes?

• Decreased triglyceride synthesis

• Increased lipolysis

• Increased blood fatty acids used by liver to produce ketones and ketoacids

• Ketones cause a sweet odor

• Ketoacids can lead to metabolic acidosis

What are the consequences of increased ketoacid production in diabetes?

• Metabolic acidosis (low blood pH)

• Compensatory increase in ventilation

• Risk of diabetic coma if untreated

What happens to protein metabolism in untreated diabetes?

• Decreased amino acid uptake by muscle

• Increased proteolysis (muscle wasting)

• Amino acids used as substrates for gluconeogenesis

Which hormones are primarily controlled by the hypothalamus and pituitary?

Hormones that are regulated via releasing or inhibiting factors from the hypothalamus affecting the anterior pituitary (e.g., ACTH, TSH, LH, FSH, GH, prolactin), and hormones released directly from the posterior pituitary (e.g., oxytocin, ADH)

How do hormones that respond directly to changes in blood constituents differ from those under hypothalamus/pituitary control?

These hormones (like insulin, glucagon, aldosterone) are released directly by endocrine glands in response to changes in blood chemistry, not primarily regulated by hypothalamic or pituitary signals.

Name the two parts of the pituitary gland and their general characteristics

Anterior pituitary - glandular tissue, produces and secretes hormones in response to hypothalamic signals.
Posterior pituitary - neural tissue, stores and releases hormones made by the hypothalamus

What is the anatomical connection between the hypothalamus and anterior pituitary?

The hypothalamic-pituitary portal system—a specialized blood vessel network that transports hypothalamic releasing/inhibiting hormones directly to the anterior pituitary.

How is the posterior pituitary connected to the hypothalamus?

By the neural stalk, through which axons from hypothalamic neurons extend, releasing hormones like ADH and oxytocin directly into the bloodstream.

What is the connecting stalk between hypothalamus and pituitary called?

infundibulum

What hormones are released by the axon termini of neurons in the posterior pituitary?

vasopressin (ADH) and oxytocin

Where are vasopressin and oxytocin synthesized?

In the cell bodies of hypothalamic neurons clustered in specific regions called nuclei.

How do vasopressin and oxytocin reach the posterior pituitary?

They are transported down the axons of hypothalamic neurons to the posterior pituitary and released into the capillary bed upon stimulation.

What triggers increased vasopressin (ADH) secretion?

Increased plasma osmolarity (main trigger) and large drops in blood pressure (less common).

What are the effects of vasopressin (ADH)?

Raises blood pressure by causing systemic vasoconstriction and increasing water reabsorption in the kidneys.

How do hypothalamic releasing and inhibiting hormones reach the anterior pituitary?

They are released into a capillary bed at the base of the hypothalamus and travel through the hypothalamic–pituitary portal system to a second capillary bed in the anterior pituitary.

What is the function of hypothalamic releasing and inhibiting hormones?

They regulate the synthesis and secretion of hormones produced by the anterior pituitary.

What are the general effects of anterior pituitary hormones?

Most are tropic hormones, meaning they regulate the growth and hormone production of other endocrine glands.

What are the hormones made by the anterior pituitary and their basic effects?

• ACTH (Adrenocorticotropic hormone) – Stimulates cortisol production in adrenal cortex

• TSH (Thyroid-stimulating hormone) – Stimulates thyroid hormone production

• LH (Luteinizing hormone) – Stimulates sex hormone production (testosterone, estrogen/progesterone)

• FSH (Follicle-stimulating hormone) – Stimulates gamete production (sperm, ova)

• GH (Growth hormone) – Promotes tissue growth, mainly via IGF-1 from liver

• Prolactin – Stimulates milk production in mammary glands

What does the term “tropic hormone” mean?

A hormone that stimulates another endocrine gland to grow and/or secrete its hormones.

What is the role of hypothalamic releasing and inhibiting hormones?

They regulate anterior pituitary hormone secretion by stimulating or inhibiting hormone production in anterior pituitary cells.

Why are hypothalamic hormones difficult to measure in systemic blood?

They act locally through the hypothalamic–pituitary portal system and are present in very low concentrations in the general circulation.

What do clinicians measure to assess endocrine function?

Hormone levels from the anterior pituitary and peripheral endocrine glands, not hypothalamic hormones.

What does CRH (corticotropin-releasing hormone) stimulate?

It stimulates the anterior pituitary to release ACTH (adrenocorticotropic hormone).

What does ACTH stimulate?

The adrenal cortex to release cortisol.

What is the CRH–ACTH–cortisol axis an example of?

A hormonal cascade regulated by negative feedback, where rising cortisol levels inhibit CRH and ACTH secretion.

What does TRH (thyrotropin-releasing hormone) stimulate?

The anterior pituitary to release TSH (thyroid-stimulating hormone).

What does thyroid-stimulating hormone (TSH) stimulate?

The thyroid gland to release thyroid hormones (T3 and T4).

What is the TRH–TSH–thyroid hormone axis an example of?

Negative feedback regulation, where increased thyroid hormone levels inhibit TRH and TSH secretion.

What is a primary endocrine disorder?

A disorder caused by a problem in the endocrine gland itself, which is the final target in a hormone axis (e.g., adrenal cortex, thyroid gland).

What is a secondary endocrine disorder?

A disorder caused by a problem in the anterior pituitary, which secretes tropic hormones that act on peripheral endocrine glands

What is a tertiary endocrine disorder?

A disorder caused by a problem in the hypothalamus, which affects the release of releasing/inhibiting hormones that control the anterior pituitary.

What positively regulates growth hormone (GH) secretion?

Growth hormone-releasing hormone (GHRH) from the hypothalamus.

What negatively regulates growth hormone (GH) secretion?

Somatostatin, which inhibits GHRH and GH secretion.

What physiological state promotes GH secretion in this course?

deep sleep

What are the two major categories of GH effects?

Growth effects and metabolic effects