6.1 Endocrine Organs and Hormones

What are the three classes of cell-to-cell chemical communication?

Endocrine: hormones released by specialised glands to act on distant target cells via the bloodstream. Paracrine: signals act on nearby cells. Autocrine: signals act on the same cell that released them.

What are the four chemical classes of endocrine hormones? Give one example of each

Proteins (e.g. insulin, gonadotrophin), Peptides (e.g. thyrotrophin-releasing hormone), Amino acid derivatives/catecholamines (e.g. epinephrine/adrenaline), and Steroids (e.g. glucocorticoids, vitamin D3).

What is the structural basis for steroid hormones, and how does this differ from peptide hormones?

Steroid hormones are derived from the cholesterol steroid nucleus (four fused rings). Peptide/protein hormones are chains of amino acids (e.g. insulin has A and B chains linked by disulfide bonds). Tyrosine derivatives such as thyroxine and adrenaline are derived from the amino acid tyrosine.

Describe the classical nuclear receptor signalling pathway for steroid hormones.

A lipid-soluble steroid ligand diffuses into the cell and binds to an intracellular receptor (often bound to heat shock protein, HSP). The receptor–ligand complex dimerises, translocates to the nucleus, and binds steroid response elements (SRE) in DNA, recruiting co-activators to drive mRNA and protein synthesis, producing the cell response.

What is the extra-nuclear (non-classical) steroid receptor pathway?

Steroid receptors located at the plasma membrane activate rapid cytoplasmic signalling cascades (e.g. Sos → Ras → Raf → MEK → ERK1/2). ERK1/2 can then enter the nucleus and phosphorylate transcription factors to alter gene expression, producing effects faster than classical genomic signalling.

Name the major endocrine organs and a key hormone secreted by each.

Hypothalamus (TRH, CRH, GnRH, GHRH, somatostatin, dopamine), Pituitary (GH, TSH, ACTH, LH, FSH, PRL, ADH, oxytocin), Thyroid (T3, T4, calcitonin), Parathyroid (PTH), Adrenal cortex (cortisol, aldosterone, androgens), Adrenal medulla (adrenaline, noradrenaline), Pancreas (insulin), Ovaries (oestradiol, progesterone), Testes (testosterone), Pineal (melatonin).

Proteins: insulin, erythropoietin. Peptides: TRH (thyrotrophin-releasing hormone). Small molecule amino acid derivatives: adrenaline, melatonin. Steroids: cortisol, testosterone.

Which endocrine organs are considered non-classical? Give examples of their hormones.

Cardiovascular system (ANP, endothelins, NO), Kidney (erythropoietin, renin), Adipose tissue (leptin, adiponectin, resistin), and Bone (FGF-23, osteocalcin) are non-classical endocrine organs that also secrete hormones.

What is the role of GnRH and what does it stimulate?

Gonadotropin-releasing hormone (GnRH) is released episodically from the hypothalamus and acts on the anterior pituitary to stimulate synthesis and release of the gonadotrophins LH (luteinising hormone) and FSH (follicle-stimulating hormone), which in turn regulate sex hormone secretion and reproductive processes in both sexes.

List the hypothalamic hormones and whether each stimulates (+) or inhibits (-) the anterior pit.

TRH (+) → TSH. CRH (+) → ACTH. GnRH (+) → LH and FSH. GHRH (+) → Growth Hormone. Somatostatin (–) → Growth Hormone. Dopamine (–) → Prolactin.

How does the posterior pituitary differ from the anterior pituitary in how it releases hormones?

The posterior pituitary releases ADH and oxytocin, which are produced by hypothalamic neurosecretory cells and transported along axons to axon terminals, where they are secreted directly into the bloodstream. The anterior pituitary instead synthesises its own hormones in response to hypothalamic releasing/inhibiting hormones delivered via the portal blood system.

List the five major anterior pituitary hormones and the target organ/effect of each.

TSH → thyroid (stimulates T3/T4 secretion). ACTH → adrenal cortex (stimulates cortisol). LH + FSH → gonads (sex hormone secretion and reproduction). GH → liver and many tissues (anabolic and growth responses). Prolactin → mammary gland (lactation; suppresses gonadal function).

What is the end effect of the TSH axis from the hypothalamus to the target tissue?

Hypothalamus releases TRH → anterior pituitary releases TSH → thyroid releases T3/T4 → increased metabolic rate and thermogenesis (heat production by the body). Cortisol and T3/T4 provide negative feedback to both the hypothalamus and pituitary.

What are T3, T4, and rT3, and how do they differ in biological activity?

Thyroxine (T4) has four iodine atoms and is the main thyroid secretion. In peripheral tissues T4 is de-iodinated to tri-iodothyronine (T3), which has 3–4× greater biological activity than T4. Alternatively, T4 can be converted to reverse-T3 (rT3), which is biologically inactive. The relative balance of T3 to rT3 determines overall thyroid hormone activity.

What type of molecules are thyroid hormones, and how are they chemically unique?

Thyroid hormones (T3 and T4) are small molecule tyrosine derivatives that are unique in containing iodine atoms in their structure. They are not steroids or peptides, but amino acid derivatives derived from tyrosine.

What are the three zones of the adrenal cortex and which hormone class does each produce?

The adrenal cortex has three zones: zona glomerulosa (outermost) produces mineralocorticoids such as aldosterone; zona fasciculata (middle, largest) produces glucocorticoids such as cortisol; zona reticularis (innermost) produces androgens. The adrenal medulla (centre) produces catecholamines.

What are the functions of aldosterone and cortisol?

Aldosterone (mineralocorticoid) promotes renal Na⁺ reabsorption and K⁺ excretion, regulating fluid and electrolyte balance. Cortisol (glucocorticoid) promotes tissue protein breakdown and mobilisation of glycerol and free fatty acids from adipose tissue, raising blood glucose in stress responses.

What are the three catecholamines of the adrenal medulla and their roles?

Adrenaline (epinephrine) is the stress hormone that activates fight-or-flight: raises blood flow to muscles, increases heart output, dilates pupils, and raises blood glucose. Noradrenaline (norepinephrine) is the main sympathetic neurotransmitter in the cardiovascular system, increasing and maintaining blood pressure. Dopamine mediates the reward response, motor control, and neuromodulation.

Why is a single serum cortisol measurement uninformative, and how is adrenal function properly tested?

Cortisol fluctuates widely and shows marked diurnal variation (highest in the morning, lowest at night), making single-point measurements unreliable. Adrenal function is properly assessed using a dynamic function test — measuring cortisol production following stimulation of the adrenal cortex by synthetic ACTH (the Short Synacthen Test).

Describe the hypothalamic-pituitary-adrenal (HPA) axis and its feedback mechanism.

Stress or the sleep/wake cycle stimulates the hypothalamus to release CRF/CRH → anterior pituitary releases ACTH → adrenal cortex produces cortisol. Cortisol feeds back negatively (–) on both the hypothalamus and anterior pituitary to inhibit further CRH and ACTH release, completing the negative feedback loop.

Compare testosterone and estradiol: source, class, and sex distribution.

Testosterone is the principal androgen (steroid), synthesised by the testes in males and ovaries in females — adult males have 7–8× more than females. Estradiol is the principal oestrogen (steroid), synthesised by the ovaries in females and testes in males; circulating levels vary throughout the menstrual cycle.

What is sex hormone-binding globulin (SHBG) and what is its clinical significance?

SHBG is a carrier protein in the blood that binds testosterone and oestrogens. Plasma SHBG is approximately twice as high in females as males. Increased SHBG results in more oestradiol-like effects (less free testosterone), while decreased SHBG results in more testosterone-like effects (more free testosterone). Changes in SHBG can therefore alter the hormonal balance without changing total hormone production.

What is the role of LH and FSH in gonadal function in both sexes?

LH and FSH (gonadotrophins from the anterior pituitary) act co-operatively in both males and females. In females: FSH stimulates follicle development; LH triggers ovulation and stimulates oestradiol and progesterone. In males: FSH supports spermatogenesis; LH stimulates Leydig cells to produce testosterone. Both are released in response to hypothalamic GnRH.