The endocrine system

What is the role of the endocrine system?

Maintains homeostasis via hormones acting on target organs.

How do endocrine glands differ from exocrine glands?

Endocrine: Ductless, hormones into blood; Exocrine: Ducts to surfaces.

Name three organs with secondary endocrine functions.

Kidney (erythropoietin, renin), liver (angiotensinogen), heart (ANP, BNP).

Where is the pituitary gland located?

Sphenoid bone; ~1 cm diameter, 0.5-1 g.

What are the two divisions of the pituitary?

Anterior (adenohypophysis), posterior (neurohypophysis).

How does the hypothalamus communicate with the posterior pituitary?

Via neurons in the hypothalamo-hypophysial tract.

How does the hypothalamus regulate the anterior pituitary?

Via portal blood vessels in the hypothalamo-hypophysial portal.

Where is the thyroid gland located?

Lateral to trachea, inferior to thyroid cartilage; two lobes with isthmus.

What hormones does the thyroid produce?

T3 (triiodothyronine), T4 (thyroxine), calcitonin.

What is required for thyroid hormone synthesis?

Iodine (from seafood, dairy, kelp).

What do parathyroid chief cells produce?

Parathyroid hormone (PTH) for calcium homeostasis.

What are the two regions of the adrenal gland?

Cortex (steroid hormones), medulla (epinephrine, norepinephrine).

What is Cushing’s syndrome?

Excess cortisol; causes weight gain, sweating, thin skin.

What are the endocrine cells of the pancreas?

Islets of Langerhans: Beta (insulin), alpha (glucagon), delta (somatostatin).

Describe the hypothalamus-pituitary-thyroid axis.

Hypothalamus (TRH) → Pituitary (TSH) → Thyroid (T3/T4); negative feedback.

What are the three structural classes of hormones?

Peptide/protein, steroid, amine.

What is the main difference between peptide and steroid hormones?

Peptide: Lipophobic, bind surface receptors; Steroid: Lipophilic, bind nuclear receptors.

Name a hormone produced by the anterior pituitary.

ACTH, FSH, LH, GH, TSH, or prolactin.

What are the four types of cell signalling?

Endocrine, paracrine, autocrine, membrane protein contact.

What is endocrine signalling?

Hormones released into blood, act on distant target cells (e.g., insulin → liver).

What is paracrine signalling?

Molecules act on nearby cells (e.g., somatostatin in pancreas).

What is autocrine signalling?

Molecules act on the same cell that released them (e.g., growth factors).

What is signal transduction?

Extracellular signal binding to receptor triggers intracellular changes.

Name the four main receptor types in cell signalling.

Ligand-gated ion channels, GPCRs, kinase-linked, nuclear receptors.

What do ligand-gated ion channels do?

Open/close to alter ion flux (e.g., Na⁺, Ca²⁺) upon ligand binding.

How do GPCRs function?

Ligand binding activates G-protein, producing second messengers (e.g., cAMP).

What is the role of kinase-linked receptors?

Ligand binding activates kinase, phosphorylating proteins (e.g., insulin receptor).

How do nuclear receptors work?

Bind lipophilic ligands, migrate to nucleus, regulate gene transcription.

What is the difference between Class I and Class II nuclear receptors?

Class I: Cytosolic, homodimers (e.g., steroid hormones); Class II: Nuclear, heterodimers with RXR (e.g., fatty acids).

Why is signal amplification important?

Enhances speed, control, and impact of signals (e.g., hormone, immune responses).

What are the three main hormone categories?

Proteins/polypeptides, steroids, amino acid-derived (thyroid hormones, catecholamines).

How are peptide hormones synthesized and stored?

Synthesized as prohormones in RER, stored in vesicles.

How are steroid hormones transported in blood?

Bound to plasma proteins.

What is the mechanism of action for thyroid hormones?

Bind nuclear receptors, promote/suppress gene transcription, synthesize new proteins.

What is response-driven negative feedback?

Hormone’s effect regulates its secretion (e.g., insulin lowers glucose → reduces insulin).

Give an example of axis-driven negative feedback.

CRH → ACTH → cortisol; cortisol inhibits CRH/ACTH.

What is positive feedback in the endocrine system?

Amplifies response until an event (e.g., oxytocin → childbirth).

What is feed-forward control?

Anticipates change before feedback (e.g., morning cortisol surge).

What stimulates ADH release?

Increased blood osmolarity (detected by hypothalamic osmoreceptors).

How does ADH affect the kidneys?

Increases aquaporin-2 in collecting ducts → more water reabsorption → less urine.

What are the effects of ADH?

Lowers blood osmolarity, increases blood volume.

What stimulates aldosterone secretion?

Low blood pressure/volume → RAAS (renin → angiotensin II → aldosterone).

What is the mechanism of aldosterone?

Binds mineralocorticoid receptor → transcribes ENaC/Na⁺/K⁺ ATPase → sodium reabsorption.

How does aldosterone affect water reabsorption?

Increases sodium reabsorption → raises osmolarity → stimulates ADH → water reabsorption.

What is the role of ANP in fluid balance?

Promotes sodium/water excretion, counteracts ADH/aldosterone.

What is the histological structure of the thyroid gland?

Follicular cells surrounding colloid-filled follicles (store thyroglobulin); parafollicular cells secrete calcitonin.

How are thyroid hormones (T3, T4) synthesized?

Tyrosine + iodine → MIT/DIT on thyroglobulin; coupling forms T3 (MIT+DIT) or T4 (DIT+DIT); stored in colloid.

How are T3/T4 transported in blood?

99.98% T4, 99.7% T3 bound to TBG, TTR, albumin; free T4 (0.02%), T3 (0.3%) active.

What are the zones of the adrenal cortex and their hormones?

Zona glomerulosa (aldosterone), zona fasciculata (cortisol), zona reticularis (androgens).

How is cortisol synthesized?

From cholesterol in zona fasciculata via enzymatic modifications; not stored, released upon synthesis.

Describe the hypothalamic-pituitary-thyroid axis.

TRH (hypothalamus) → TSH (pituitary) → T3/T4 (thyroid); high T3/T4 inhibit TRH/TSH.

Describe the hypothalamic-pituitary-adrenal axis for cortisol.

CRH (hypothalamus) → ACTH (pituitary) → cortisol (zona fasciculata); high cortisol inhibits CRH/ACTH.

What is the mechanism of action for T3?

Enters cell, binds nuclear receptor, initiates transcription → mRNA → new proteins.

How does cortisol act on target cells?

Binds glucocorticoid receptor (cytoplasm), translocates to nucleus, initiates/represses gene expression.

What are the metabolic effects of thyroid hormones?

Increase Na⁺/K⁺ ATPase, glucose absorption, glycogenolysis, gluconeogenesis, lipolysis; net catabolic protein turnover.

What are the effects of cortisol?

Stimulates gluconeogenesis, proteolysis, lipolysis; increases calcium excretion; suppresses immunity.

Why are thyroid hormones essential for growth?

Promote CNS maturation and bone growth (fetal/neonatal).

What are the effects of untreated congenital hypothyroidism?

Short stature, delayed bone age/puberty, infertility, cognitive impairment, thickened skin, enlarged tongue.

What does a high TSH level in neonatal screening suggest?

Hypothyroidism (e.g., underdeveloped thyroid gland).

How is congenital hypothyroidism treated?

Levothyroxine by 3 weeks, monitor TSH/T4 levels.

What are the symptoms of hyperthyroidism?

High metabolic rate, sweating, nervousness, tremor, tachycardia, heat sensitivity, weight loss, bulging eyes, scanty periods.

How does radioactive iodine (¹³¹I) treat hyperthyroidism?

Oral, taken up by thyroid, emits β-radiation to damage follicular cells; lasts ~2 months, may cause hypothyroidism.

How do thiourelene drugs (e.g., carbimazole) work?

Inhibit thyroperoxidase → reduce iodination of thyroglobulin → lower T3/T4 synthesis; act over 3-4 weeks.

What is the first-line treatment for hypothyroidism?

Levothyroxine; mimics T4, converts to T3, restores metabolism/growth.

Why is insulin administered by injection for T1D?

Peptide hormone; degraded in GI tract if taken orally.

What are the types of insulin by duration of action?

Rapid-acting (3-4h), short-acting (6-8h), intermediate (13-20h), long-acting (>24h).

How does metformin treat T2D?

Reduces hepatic gluconeogenesis, increases muscle glucose uptake, reduces gut carbohydrate absorption; activates AMP-kinase.

What is the mechanism of thiazolidinediones (e.g., pioglitazone)?

PPARγ agonists → upregulate lipoprotein lipase, fatty acid transporters, glucose transporter 4 → increase glucose uptake.

How do sulphonylureas (e.g., glibenclamide) work?

Block ATP-sensitive K⁺ channels in β-cells → depolarization → Ca²⁺ influx → insulin release.

What are incretins, and how do gliptins enhance their action?

GLP-1/GIP stimulate insulin, inhibit glucagon; gliptins inhibit DPP-4 → increase incretin levels.

How do GLP-1 receptor agonists (e.g., semaglutide) work?

Mimic GLP-1, stimulate GPCR → increase insulin, reduce glucagon, slow gastric emptying, promote satiety.

What is the mechanism of gliflozins (e.g., dapagliflozin)?

Inhibit SGLT2 in proximal tubule → increase renal glucose excretion.

What hormones are replaced in Addison’s disease?

Hydrocortisone (cortisol), fludrocortisone (aldosterone), DHEA (androgens).

What causes Cushing’s syndrome?

Pituitary/adrenal tumours or long-term high-dose corticosteroids; leads to excess cortisol.

How do combined oral contraceptives prevent pregnancy?

Inhibit GnRH (hypothalamus), FSH/LH (pituitary) → prevent ovulation; reduce implantation likelihood.