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Classification and Mechanism of Action of Hormones

Hormona

For medical students3 min readUpdated 2026-10-10

Hormones are biologically active signaling molecules that regulate cellular function. Their basic classification relies on physicochemical properties (solubility), which directly determines how the molecule transmits its signal: by remaining at the cell membrane or by penetrating the cell interior.

HydrophilicDo not enter the cell. Include proteins, peptides, and most amino acid derivatives.

HydrophobicFreely cross the plasmalemma. These include steroids, prostaglandins, and thyroid hormones.

SpecificityDepends on the presence of the correct receptor, signaling cascade, and final target proteins.

ReceptionOccurs either on the external surface of the plasmalemma or within the cell cytosol.

Physicochemical Classification and Chemical Structure

Globally, all hormones are divided into two large groups based on their affinity for aqueous and lipid environments.

Hydrophilic Hormones

This extensive group includes molecules that are highly soluble in water. Structurally, they are divided into:

Proteins and peptides. These include absolutely all hypothalamic hormones (peptides), as well as secretions of the anterior and intermediate lobes of the pituitary gland (tropic protein hormones, ACTH, MSH, and lipotropin peptides). The thyroid gland secretes the peptide calcitonin, and the parathyroid glands secrete the polypeptide parathyroid hormone (PTH). The pancreas produces a spectrum of polypeptides: insulin, glucagon, somatostatin, VIP, and pancreatic polypeptide (PP). The kidneys secrete renin and the glycoprotein erythropoietin. This group also includes thymic protein hormones, gastrointestinal APUD system peptides (gastrin, secretin, cholecystokinin), and brain neuropeptides.
Amino acid derivatives. The adrenal medulla secretes epinephrine and norepinephrine. Melatonin (the main pineal hormone) and serotonin are derived from tryptophan, while histamine is derived from histidine (synthesized by basophils, mast cells, and GI enteroendocrine cells). Despite containing a cyclic radical, most of these are hydrophilic.

Hydrophobic (Lipophilic) Hormones

This group is relatively small and represented by three classes:

Steroid hormones. Derivatives of cholesterol. These include corticosteroids (mineralocorticoid aldosterone, glucocorticoid hydrocortisone, androgen androstenedione) and sex hormones (estrogens, androgens, progesterone).
Prostaglandins. Derivatives of the fatty acid arachidonic acid containing a cyclopentane ring. They are produced in many tissues (including the kidneys) and exhibit a vast array of effects.
Thyroid hormones (thyroxine, triiodothyronine). Formally derivatives of the amino acid tyrosine, they are an exception—these molecules exhibit pronounced hydrophobic properties.

Mechanism of Action of Hydrophilic Hormones

Because proteins, peptides, and catecholamines cannot cross the lipid bilayer of the membrane, they interact with receptors on the surface of the plasmalemma. The signal is transmitted inside the cell via a cascade of second messengers.

Basic steps of signal transmission:

Reception. The hormone binds to a receptor on the outer membrane.
Enzyme activation. The complex alters the activity of a membrane-bound enzyme (e.g., adenylyl cyclase).
Messenger generation. Adenylyl cyclase converts ATP into a second messenger—cyclic adenosine monophosphate (cAMP)—whose concentration in the cytoplasm changes sharply.
Protein kinase activation. The messenger (cAMP) stimulates a regulatory enzyme (protein kinase).
Phosphorylation. Protein kinases attach a phosphate group to structural or regulatory proteins in the cytoplasm or nucleus.

Phosphorylation changes the conformation of the target protein. If the target is an enzyme, the reaction rate changes (e.g., epinephrine triggers lipid breakdown in this manner). If the target is a nuclear protein, gene activity is modulated.

Mechanism of Action of Hydrophobic Hormones

Steroids and thyroid hormones freely diffuse across the plasmalemma directly into the cytosol.

Inside the cell, the hormone binds to a specific receptor. If no matching receptor is present, the molecule simply diffuses back out.
Successful binding stimulates further influx of the hormone into the cell down its concentration gradient.
The hormone-receptor complex translocates to the nucleus, where it interacts with regulatory regions of DNA.

As a result, the rate of mRNA transcription changes, leading to the activation or inhibition of the synthesis of new proteins.

Specificity and Morphological Classification

The targeted, strictly selective action of a hormone depends on four levels of specificity:

Receptor localization (which cells express them).
Type of intracellular signaling triggered.
Specific final target proteins.
Nature of the response of each chain element (activation or inhibition).

Morphologically, sources of hormones are divided into two main groups:

Central endocrine organs: hypothalamus, pituitary gland (hypophysis), pineal gland ( epiphysis ).
Peripheral endocrine glands: thyroid and parathyroid glands, adrenal glands.

Mnemonic

The three classes of hydrophobic (lipophilic) hormones can be remembered by the acronym SPT: Steroids, Prostaglandins, Thyroid hormones.

Frequently asked questions

Which hormones are synthesized from the amino acid tyrosine?

The following tyrosine derivatives are formed from the amino acid tyrosine:

Catecholamines: dopamine, norepinephrine, epinephrine;
Iodine-containing (thyroid) hormones of the thyroid gland: thyroxine and triiodothyronine.

These substances belong to the chemical class of amino acid derivatives. Thyroid hormones are an exception among amino acid derivatives and exhibit hydrophobic properties; most other amino acid derivatives are hydrophilic.

Which second messengers participate in the signal transduction of hydrophilic hormones?

Intracellular signaling molecules (messengers), whose concentrations change in response to hormone binding to a membrane receptor, participate in hydrophilic hormone signal transduction.

Intracellular second messengers include:

cAMP — cyclic adenosine monophosphate.
cGMP — cyclic guanosine monophosphate.
IP3 — inositol trisphosphate (inositol-1,4,5-trisphosphate).
DAG — diacylglycerol.
Ca²⁺ — calcium ions.

These substances transmit signals to specific proteins and enzymes (such as protein kinases), producing the final alteration in metabolic rate.

Which membrane enzymes are activated when hydrophilic hormones bind to receptors?

When hydrophilic hormones bind to receptors on the outer surface of the membrane, specific membrane enzymes are activated, initiating a cascade of reactions.

The following effector enzymes are activated in signal transduction systems:

Adenylyl cyclase — converts ATP to cAMP.
Guanylyl cyclase — catalyzes the formation of cGMP from GTP.
Phospholipase C — cleaves the membrane phospholipid phosphatidylinositol-4,5-bisphosphate to form IP3 and DAG.

Activation of these enzymes frequently occurs with the participation of G-proteins and leads to the synthesis of intracellular second messengers.

Why are thyroid hormones considered exceptions?

Chemically, they are derivatives of the amino acid tyrosine, but physico-chemically they behave like lipophilic molecules, penetrating the cell membrane and binding to intracellular receptors.

How does a hydrophilic hormone alter cell function without entering the cell?

It transmits a signal to a receptor on the plasmalemma, which activates second messengers (such as cAMP). These trigger a phosphorylation cascade, altering the activity of intracellular enzymes.

What happens if there is no receptor for a steroid hormone in the cell cytosol?

The hormone will freely pass through the membrane into the cell, but finding no target, it will exert no effect and simply diffuse back out into the extracellular environment.

Go deeper

Organs with mixed endocrine function and the diffuse endocrine system (APUD)
Chemical structure of arachidonic acid derivatives (prostaglandins)
Alternative intracellular signaling pathways (beyond the cAMP-dependent cascade)
Histological structure of central endocrine organs (pituitary, pineal gland)