Hormone Biochemistry
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Direct answer
Insulin circulates free, acts within minutes at a surface receptor and is cleared in five to eight minutes; cortisol rides on transcortin and acts for hours through nuclear receptors — the contrast encodes the whole classification. Peptide hormones (insulin, PTH, pituitary hormones) are stored preformed in vesicles, water-soluble and membrane-bound; steroids (cortisol, aldosterone, sex steroids) are made from cholesterol on demand, travel on carriers (CBG, SHBG, albumin) and act on intracellular receptors as transcription regulators. The amine derivatives split: catecholamines behave like peptides, while thyroid hormone — tyrosine-derived, iodinated, lipophilic — is the classic exception, binding nuclear receptors, with over 99.9% of circulating T4 carried on thyroxine-binding globulin. Only the free fraction is biologically active.
What you must remember
- Class behaviour table (in prose): peptides — preformed stores, membrane receptors, second messengers, half-lives of minutes; steroids — synthesised on demand (no storage), carrier-bound, hormone response elements, half-lives of hours; thyroid hormone — synthesised ahead and stored uniquely in colloid, carrier-bound, nuclear receptor.
- Transport proteins: thyroxine-binding globulin (T4, T3), transcortin or CBG (cortisol), sex hormone-binding globulin (testosterone and oestradiol), albumin as the promiscuous reserve — pregnancy and oral contraceptives raise TBG and CBG, raising total hormone while free stays normal.
- Measurement principles: sandwich (two-site, non-competitive) immunoassays suit large peptides like TSH; competitive assays suit small molecules like T4 and steroids; radioimmunoassay earned Yalow and Berson the 1977 Nobel Prize.
- Feedback axes: hypothalamic-releasing hormone → pituitary trophin → target gland hormone, with negative feedback at both levels; primary gland failure raises the trophin, secondary (pituitary) failure lowers everything.
- Pulsatility: GnRH must pulse; continuous exposure down-regulates gonadotrophs — the deliberate mechanism of leuprolide in precocious puberty and prostate cancer.
- Permissive interactions: cortisol permits catecholamine vasoconstriction and lipolysis; thyroid hormone potentiates catecholamine effects — the reason thyrotoxicosis mimics adrenergic excess.
- Processing gives diagnostics: proinsulin cleavage yields equimolar C-peptide (a marker of endogenous secretion); T4 to T3 conversion by 5'-deiodinase generates the active hormone peripherally.
- Free hormone principle: the unbound fraction determines both action and clearance, so free T4, free testosterone or corrected values beat totals whenever binding proteins shift.
A worked case: the pregnant woman with a high total T4
A woman at 14 weeks of gestation has a total thyroxine of 16 µg/dL (high) but feels well, with a normal free T4 and a slightly low TSH. Oestrogen increases hepatic synthesis of thyroxine-binding globulin, so more T4 is bound and the measured total rises — but the free, active fraction is unchanged, and the pituitary's verdict (a TSH at the low end of normal for pregnancy) confirms euthyroidism. Interpretive discipline saves this patient from misdiagnosis: in pregnancy, always order free T4 with TSH and use trimester-specific reference ranges; total hormone assays are traps in any state that changes binding proteins — the oral contraceptive pill (high TBG), nephrotic syndrome (lost TBG) or acromegaly-altered clearance. The same logic governs cortisol: raised total in pregnancy from CBG without Cushingoid physiology, and low total in nephrotic-range proteinuria without adrenal failure.
Where students slip
The classification examiners actually probe is the amine family's split: catecholamines act like peptides (membrane receptors, seconds), thyroid hormone like steroids (nuclear receptor, delayed) — merging them into one behaviour loses the discriminating mark. Second, "stored versus synthesised on demand" separates peptides (stored) from steroids (no storage — the adrenal cannot hoard cortisol), a favourite viva one-liner. Third, C-peptide's use is reversed in factitious hypoglycaemia: exogenous insulin drives glucose down with suppressed C-peptide, while insulinoma shows paired elevation. Fourth, GnRH's continuous administration suppresses rather than stimulates — candidates forget down-regulation and predict stimulation. Fifth, the axis rule "primary high, secondary low" applies to the trophin: primary hypothyroidism raises TSH; and in every axis, the trophin's direction is the map to the lesion's level.
Frequently asked questions
Why do peptide hormones act faster than steroid hormones?
They are preformed and act at membrane receptors through second messengers within seconds to minutes, while steroids require new gene transcription over hours.
What happens to total thyroxine in pregnancy, and why?
It rises because oestrogen increases thyroxine-binding globulin; free T4 remains normal, which is why free assays with trimester-specific TSH ranges are used.
What distinguishes sandwich from competitive immunoassays?
Sandwich (two-site) assays measure large antigens like TSH with high sensitivity; competitive assays are needed for small molecules like steroids and T4.
Why must GnRH be delivered in pulses?
Continuous GnRH down-regulates pituitary gonadotroph receptors, suppressing LH and FSH — the basis of leuprolide therapy.
What does C-peptide measure?
Equimolar endogenous insulin secretion, distinguishing insulinoma (high insulin with high C-peptide) from injected insulin (high insulin with low C-peptide).