NCERT grounding
NCERT Class 11, Chapter 19 §19.4 — Mechanism of Hormone Action — opens with a single load-bearing sentence: hormones produce their effects on target tissues by binding to specific proteins called hormone receptors located in the target tissues only. The text then divides receptors into two locations — on the cell membrane (membrane-bound) or inside the cell (intracellular, mostly nuclear) — and explains that binding forms a hormone-receptor complex which sets off biochemical changes (Figures 19.5 a and b). The chapter also classifies hormones into four chemical groups (peptides/proteins, steroids, iodothyronines, amino-acid derivatives) and links each group to the receptor type it uses.
"Hormones which interact with membrane-bound receptors normally do not enter the target cell, but generate second messengers… Hormones which interact with intracellular receptors mostly regulate gene expression or chromosome function."
NCERT Class 11, §19.4
NIOS Biology Chapter 17 supplements this with the feedback-loop view (§17.10), reinforcing that hormone levels themselves are controlled by negative feedback acting on the hypothalamic-pituitary-target axis — but the cellular mechanism description in NCERT remains the syllabus-anchor for NEET. Exercise question 8 of the same chapter asks students to "briefly mention the mechanism of action of FSH", which is essentially a request to verbalise the membrane-receptor route for a protein hormone.
Two-pathway scheme
Every endocrine signal in the human body resolves to one of two cellular routes. The choice is not made by the gland but by the chemistry of the hormone — specifically, whether it can dissolve in the lipid bilayer of the plasma membrane. Water-soluble hormones (peptides, polypeptides, proteins and amino-acid derivatives such as adrenaline) cannot cross the membrane and must therefore signal from outside. Lipid-soluble hormones (steroids and iodothyronines/thyroid hormones) diffuse straight through the bilayer and bind receptors waiting in the cytosol or nucleus.
The two routes differ in speed, duration and the molecular consequence of receptor binding. The surface-receptor route works in seconds-to-minutes through pre-existing enzymes and second messengers; the intracellular route works in minutes-to-hours by switching genes on or off. NEET frequently tests this distinction in disguise — by giving you a hormone and asking which route it uses, or by giving you a route and asking which hormone fits.
Membrane-bound receptor
Surface route
Peptides, proteins, amino-acid derivatives
- Receptor sits on plasma membrane outer face
- Hormone does NOT enter the cell
- Generates second messengers (cAMP, IP3, Ca2+)
- Acts via pre-formed enzymes (e.g., protein kinase A)
- Effect within seconds to minutes; signal amplified
- Examples: insulin, glucagon, FSH, LH, ACTH, ADH, adrenaline
Intracellular receptor
Genomic route
Steroids, iodothyronines
- Receptor sits in cytosol or nucleus
- Hormone DOES enter the cell (lipid-soluble)
- Hormone-receptor complex binds DNA
- Regulates gene expression / chromosome function
- Effect over minutes to hours; longer-lasting
- Examples: cortisol, testosterone, oestradiol, progesterone, T3, T4
Membrane-bound receptor route — step-by-step
When a water-soluble hormone reaches its target cell, it docks into the extracellular domain of a transmembrane receptor. The receptor's intracellular tail then activates a coupled G-protein (or a tyrosine kinase, depending on receptor class). The G-protein in turn activates the membrane enzyme adenylate cyclase, which converts ATP into cyclic AMP (cAMP) — the prototype second messenger first described by Sutherland for the action of glucagon and adrenaline on liver cells.
cAMP then activates protein kinase A, which phosphorylates a panel of target enzymes — switching some on, others off. The net result is a coordinated change in cellular metabolism: in a liver cell, for example, glycogen phosphorylase becomes active and glycogen synthase becomes inactive, so glycogen is broken down to glucose. Crucially, the cascade amplifies the signal: one hormone molecule on the outside can give rise to hundreds of cAMP molecules, each activating a kinase, each phosphorylating many substrate enzymes. This amplification is why minute (nanomolar) blood concentrations of a peptide hormone can produce large physiological responses.
Membrane-bound receptor cascade (e.g., glucagon, adrenaline, FSH)
-
Step 1
Hormone binds surface receptor
Water-soluble hormone docks into the extracellular domain; does not enter the cell.
First messenger -
Step 2
G-protein activated
Receptor's cytoplasmic tail exchanges GDP for GTP on the α-subunit of a coupled G-protein.
Transduction -
Step 3
Adenylate cyclase fires
Gα-GTP activates adenylate cyclase in the membrane; ATP → cAMP.
Enzyme cascade -
Step 4
cAMP & protein kinase A
cAMP releases catalytic subunits of PKA, which phosphorylate target enzymes.
Second messenger -
Step 5
Cellular response
Glycogenolysis, secretion, contraction — depending on cell type. Signal amplified ~104×.
Physiological effect
Figure 1. Membrane-bound receptor pathway used by water-soluble hormones. The hormone (first messenger) does not enter the cell; the surface receptor activates a G-protein, then adenylate cyclase, which generates cAMP. cAMP activates protein kinase A, which phosphorylates target enzymes — producing a cellular response within seconds and amplifying the signal roughly ten-thousand-fold.
Intracellular receptor route — step-by-step
Steroids (cortisol, aldosterone, testosterone, oestradiol, progesterone) and thyroid hormones (T3, T4) are small and lipid-soluble. They cross the plasma membrane by simple diffusion and meet their receptor inside the cell. Steroid receptors are typically cytosolic and translocate to the nucleus on binding; thyroid-hormone receptors are usually already in the nucleus bound to DNA.
The hormone-receptor complex acts as a transcription factor. Its DNA-binding domain recognises a specific hormone-response element in the promoter of target genes, recruiting (or releasing) RNA polymerase II and so altering the transcription rate. New mRNA is exported, translated into new protein, and the protein executes the physiological response. Because every step requires synthesis, the effect takes minutes to hours to appear — but the new proteins persist, so the response is durable.
Figure 2. Intracellular-receptor pathway used by steroids and thyroid hormones. The hormone diffuses through the lipid bilayer, binds a cytosolic (or nuclear) receptor, and the hormone-receptor complex acts as a transcription factor on a hormone-response element — modulating gene expression and producing new protein. NEET 2019 marked this as "binding to DNA and forming a gene-hormone complex".
Second messengers — the inside relay
NCERT names three second messengers explicitly: cyclic AMP, IP3 and Ca2+. cAMP is the workhorse for hormones using adenylate cyclase — glucagon, adrenaline (β-adrenergic), ACTH, FSH, LH, TSH, ADH (kidney V2 receptor) and PTH. Hormones whose receptor activates phospholipase C instead generate IP3, which releases Ca2+ from the endoplasmic reticulum; the Ca2+ then binds calmodulin and activates a separate set of kinases. Adrenaline acting on α1-adrenergic receptors, and angiotensin II on its AT1 receptor, use this IP3/Ca2+ arm.
cyclic AMP (cAMP)
Made from ATP by adenylate cyclase; activates protein kinase A.
Used by glucagon, adrenaline (β), FSH, LH, ACTH, TSH, ADH (V2), PTH.
Most NEET-cited second messengerIP3
Inositol 1,4,5-trisphosphate, released by phospholipase C.
Opens Ca2+ channels on the endoplasmic reticulum.
Lipid-derived messengerCa2+
Released by IP3 from ER; binds calmodulin.
Activates Ca2+/calmodulin-dependent kinases; triggers secretion, contraction.
Universal intracellular signal104×
Signal amplification
A single hormone molecule on a surface receptor can ultimately trigger thousands of phosphorylated substrate molecules through the G-protein → cAMP → PKA cascade — which is why peptide hormones are effective at picomolar to nanomolar blood concentrations.
Receptor specificity, up- and down-regulation
NCERT states the specificity rule cleanly: "Each receptor is specific to one hormone only." Specificity is therefore not a property of the hormone (which circulates everywhere in blood) but of the receptor — only cells that express that receptor can read the message. This is why insulin acts on muscle, adipose and liver but not, say, on red blood cells, and why ADH acts on the collecting duct but not on neurons.
Receptor numbers themselves are dynamic. Prolonged exposure to a high hormone concentration typically down-regulates receptor density (a target cell removes receptors from the surface by endocytosis), so the response weakens — this is one mechanism of insulin resistance in type-2 diabetes. Conversely, chronically low hormone levels can up-regulate receptor number, restoring sensitivity. Both processes operate on top of the negative feedback loops described in NIOS §17.10, where the hypothalamus and pituitary themselves adjust hormone release in response to circulating levels.
*Adrenaline is a tyrosine derivative — water-soluble, like peptides, and uses surface receptors despite being a small molecule.
Worked examples
Adrenaline (epinephrine) is an amino-acid derivative, yet — unlike thyroxine (also a tyrosine derivative) — it uses a membrane-bound receptor. Explain.
Although both are made from tyrosine, the chemical modifications they undergo determine solubility. Adrenaline retains its catechol-amine character and is water-soluble; it cannot cross the plasma membrane and therefore signals via a surface β- or α-adrenergic receptor, generating cAMP or IP3. Thyroid hormones (T3, T4) are iodinated and joined together, becoming lipid-soluble; they cross the membrane and bind intracellular (nuclear) receptors that regulate gene expression. The receptor location is set by solubility, not by the precursor amino acid.
Briefly mention the mechanism of action of FSH (NCERT Class 11 Exercise 8).
FSH is a glycoprotein hormone secreted by the anterior pituitary. Being water-soluble, it binds the FSH-receptor on the surface of granulosa cells in the ovary or Sertoli cells in the testis. The receptor is G-protein coupled; binding activates adenylate cyclase, raises intracellular cAMP, and activates protein kinase A. PKA phosphorylates target enzymes and transcription factors that promote follicular growth and oestrogen synthesis in females and support spermatogenesis in males.
A drug blocks adenylate cyclase in liver cells. Which one of the following hormones will lose its glucose-mobilising effect — insulin, glucagon, cortisol, or thyroxine?
Glucagon. Glucagon is a peptide hormone whose surface receptor activates adenylate cyclase to make cAMP, which drives glycogenolysis through PKA. Block adenylate cyclase and the cAMP-dependent cascade collapses. Cortisol and thyroxine reach the genome through intracellular receptors (cAMP-independent), and insulin uses a different receptor (tyrosine-kinase-coupled) — none of these would be affected by blocking adenylate cyclase alone.
Why does cortisol take longer to act than adrenaline even though both are released from the adrenal gland in response to stress?
Adrenaline (from the adrenal medulla) is water-soluble and acts through surface receptors and cAMP — pre-formed enzymes are phosphorylated within seconds, producing immediate effects (raised heart rate, glycogenolysis, vasoconstriction). Cortisol (from the adrenal cortex) is a steroid; it crosses the cell membrane, binds an intracellular receptor and modulates gene transcription. Because new mRNA and protein synthesis are required, cortisol effects (gluconeogenesis, anti-inflammation, immunosuppression) appear over minutes to hours but persist much longer than the adrenaline burst.