Physicochemical classification and chemical structure
Globally, all hormones are divided into two large groups depending on their affinity for aqueous and lipid environments.
- Hydrophilic hormones
This extensive group includes molecules that are highly soluble in water. According to their chemical structure, 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. The pancreas produces a whole spectrum of polypeptides: insulin, glucagon, somatostatin, VIP, and PP. The kidneys secrete renin and the glycoprotein erythropoietin. This group also includes thymic protein hormones, peptides of the gastrointestinal APUD system (gastrin, secretin, cholecystokinin), and brain neuropeptides.
- Amino acid derivatives. The adrenal medulla secretes epinephrine and norepinephrine. Melatonin (the main pineal hormone) and serotonin are formed from tryptophan, while histamine is formed from histidine (synthesized by basophils, mast cells, and gastrointestinal endocrinocytes). Despite the presence of a cyclic radical, most of them are hydrophilic.
- Hydrophobic (lipophilic) hormones
This group is relatively small and represented by three classes:
- Steroid hormones. These are cholesterol derivatives. They include corticosteroids (the mineralocorticoid aldosterone, the glucocorticoid hydrocortisone, the androgen androstenedione) and sex hormones (estrogens, androgens, progesterone).
- Prostaglandins. Derivatives of the fatty acid arachidonic acid, containing a cyclopentane ring. Formed in many tissues (including the kidneys) and possess a tremendous variety of effects.
- Thyroid hormones (thyroxine, triiodothyronine). Formally, they are derivatives of the amino acid tyrosine, but this is an exception — the 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 stages of signal transmission:
- Reception. The hormone binds to the receptor on the outer membrane.
- Enzyme activation. The complex alters the activity of a membrane-bound enzyme (e.g., adenylate cyclase).
- Messenger generation. Adenylate cyclase converts ATP into a second messenger — cyclic adenosine monophosphate (cAMP), the concentration of which in the cytoplasm changes dramatically.
- 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 alters the conformation of the target protein. If the target is an enzyme, the reaction rate changes (for example, epinephrine triggers fat 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 through the plasmalemma directly into the cytosol.
- Inside the cell, the hormone binds to a specific receptor. If a suitable receptor is not present, the molecule simply diffuses back out.
- Successful binding stimulates further influx of the hormone into the cell along the 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:
- Localization of receptors (on which cells they are expressed).
- Type of triggered intracellular signaling.
- Specific final target proteins.
- Nature of the reaction of each element in the chain (activation or inhibition).
Morphologically, sources of hormones are divided into two main groups:
- Central endocrine organs: hypothalamus, pituitary gland, pineal gland.
- Peripheral endocrine glands: thyroid and parathyroid glands, adrenal glands.
Briefly: answers to topical questions
Which hormones are synthesized from the amino acid tyrosine?
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), the concentration of which changes in response to hormone binding to a membrane receptor, participate in the signal transduction of hydrophilic hormones.
The role of second messengers inside the cell is performed by:
- cAMP — cyclic adenosine monophosphate.
- cGMP — cyclic guanosine monophosphate.
- IP3 — inositol trisphosphate (inositol-1,4,5-trisphosphate).
- DAG — diacylglycerol.
- Ca²⁺ — calcium ions.
These substances transmit the signal to specific proteins and enzymes (e.g., protein kinases), ensuring the final change in metabolic rate.
Which membrane enzymes are activated upon binding of hydrophilic hormones to receptors?
Upon binding of hydrophilic hormones to receptors on the outer surface of the membrane, specific membrane enzymes that trigger a reaction cascade are activated.
The following effector enzymes are activated in signal transduction systems:
- Adenylate cyclase — converts ATP to cAMP.
- Guanylate cyclase — catalyzes the formation of cGMP from GTP.
- Phospholipase C — hydrolyzes the membrane phospholipid phosphatidylinositol 4,5-bisphosphate to form IP3 and DAG.
Activation of these enzymes often occurs with the participation of G proteins and leads to the synthesis of intracellular secondary messengers.
You can remember the three classes of hydrophobic (lipophilic) hormones using the abbreviation SPT: Steroids, Prostaglandins, Thyroid hormones.
Class and exam questions
Why are thyroid hormones classified as exceptions?
By chemical nature, they are derivatives of the amino acid tyrosine, but physico-chemically they behave like lipophilic molecules, penetrating the membrane and binding to intracellular receptors.
How does a hydrophilic hormone change cell function without penetrating it?
It transmits a signal to the receptor on the plasmalemma, which activates secondary messengers (e.g., cAMP). They trigger a phosphorylation cascade, changing the activity of intracellular enzymes.
What will happen if there is no receptor for a steroid hormone in the cell cytosol?
The hormone will freely pass through the membrane inside, but, having found no target, it will have no effect and will simply diffuse back into the extracellular environment.
What else to study on this topic
- Organs with mixed endocrine function and the diffuse endocrine system (APUD)
- Chemical structure of arachidonic acid derivatives (prostaglandins)
- Alternative pathways of intracellular signaling (besides the cAMP-dependent cascade)
- Histological structure of central endocrine organs (pituitary gland, pineal gland)
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