17.2 Hormones

Types and Functions of Hormones

Hormones are chemical messengers released into the bloodstream that regulate processes throughout the body. They fall into three structural categories, and that structure determines how they interact with target cells.

Types of Hormones by Structure

Peptide and protein hormones are chains of amino acids that range from just a few amino acids to hundreds. They're synthesized by ribosomes, just like other proteins. Because they're water-soluble, they can't cross the cell membrane on their own. Examples include insulin, growth hormone, and antidiuretic hormone (ADH).

Steroid hormones are derived from cholesterol, which makes them lipid-soluble. That lipid solubility is the key detail: they can diffuse directly through the phospholipid bilayer of cell membranes to reach intracellular receptors. Examples include cortisol, testosterone, and estrogen.

Amine hormones are derived from the amino acids tyrosine or tryptophan. This category includes two subgroups that behave very differently:

• Catecholamines (epinephrine, norepinephrine) are water-soluble and act like peptide hormones, binding to membrane receptors.
• Thyroid hormones ($T_3$ and $T_4$) are lipid-soluble and act more like steroid hormones, crossing the membrane and binding to intracellular receptors.

Intracellular vs. Membrane Receptors

The structure of a hormone determines where its receptor is located, which in turn determines how the signal reaches the cell's machinery.

Intracellular receptors are found in the cytoplasm or nucleus. Lipid-soluble hormones (steroids and thyroid hormones) pass through the membrane and bind these receptors directly. The hormone-receptor complex then acts as a transcription factor, binding to DNA and regulating gene expression. This mechanism is slower but produces longer-lasting effects because it changes which proteins the cell makes.

Cell membrane receptors sit on the surface of the target cell. Water-soluble hormones (peptides, proteins, and catecholamines) can't cross the membrane, so they bind to these external receptors instead. That binding triggers intracellular signaling cascades using second messengers like cAMP or $IP_3$, which amplify the signal inside the cell. The responses tend to be faster but shorter-lived than those from intracellular receptors.

A target cell is any cell that has the specific receptor for a given hormone. If a cell lacks the receptor, the hormone has no effect on it, even if it's circulating right past it in the blood.

Hormone Signaling and Regulation

Hormone Signaling Pathways

Both major second-messenger pathways start the same way: a hormone binds a G protein-coupled receptor (GPCR) on the cell surface, which activates an associated G protein. What happens next depends on the pathway.

cAMP (cyclic adenosine monophosphate) pathway:

1. Hormone binds to a GPCR, activating the associated G protein.
2. The activated G protein stimulates adenylyl cyclase, an enzyme that converts $ATP$ to $cAMP$.
3. $cAMP$ activates protein kinase A (PKA).
4. PKA phosphorylates target proteins, modifying their activity and producing the cellular response (e.g., glycogen breakdown, changes in lipid metabolism).

$IP_3$ (inositol triphosphate) pathway:

1. Hormone binds to a GPCR, activating the associated G protein.
2. The activated G protein stimulates phospholipase C (PLC), which cleaves the membrane lipid $PIP_2$ into two second messengers: $IP_3$ and DAG (diacylglycerol).
3. $IP_3$ travels through the cytoplasm and binds to receptors on the endoplasmic reticulum, triggering the release of stored $Ca^{2+}$.
4. The rise in intracellular calcium, together with DAG, activates protein kinase C (PKC), which phosphorylates target proteins and produces the cellular response (e.g., neurotransmitter release, smooth muscle contraction).

Factors in Hormone Response

Even when a hormone reaches a target cell, several factors determine how strong the response will be:

• Hormone concentration in the blood: Higher concentrations generally produce a greater response, but only up to a point. Once all available receptors are occupied, the response plateaus (saturation).
• Receptor availability and affinity:
  • The number of receptors on the cell surface sets an upper limit on the response.
  • The affinity (binding strength) between hormone and receptor influences how effectively signal transduction begins.
• Post-receptor signaling efficiency: The response also depends on whether the necessary intracellular enzymes (adenylyl cyclase, PLC, PKA, PKC) and substrates ($ATP$, $PIP_2$) are available in sufficient quantities.
• Desensitization and downregulation: With prolonged hormone exposure, cells reduce their sensitivity. Receptors can be internalized or degraded, decreasing the number on the cell surface and weakening the response over time. This is why chronically elevated hormone levels don't keep producing the same effect.

Regulation of Hormone Production

The body uses several mechanisms to keep hormone levels within a functional range:

Negative feedback loops are the most common regulatory mechanism. When hormone levels rise above the set point, that increase inhibits further production and release from the endocrine gland. When levels fall, production ramps back up. For example, rising $T_3$ and $T_4$ levels inhibit the release of thyroid-stimulating hormone (TSH) from the anterior pituitary, which in turn reduces thyroid hormone production.

Positive feedback loops are rare in the endocrine system. Instead of shutting down, rising hormone levels stimulate even more release, creating a self-amplifying cycle. The classic example is oxytocin during childbirth: oxytocin stimulates uterine contractions, which push the baby against the cervix, which triggers more oxytocin release. The cycle only breaks when the baby is delivered.

Neural stimuli allow the nervous system to directly trigger hormone release. The hypothalamus controls the anterior pituitary by secreting releasing hormones (like GHRH, which stimulates growth hormone release) and inhibiting hormones (like somatostatin, which suppresses it).

Humoral stimuli involve changes in blood levels of ions, nutrients, or other substances. For example, rising blood glucose stimulates insulin secretion from pancreatic beta cells, while falling blood glucose stimulates glucagon secretion from alpha cells. Together, these responses maintain glucose homeostasis.

Endocrine System Overview

Components and Functions

The endocrine system is made up of hormone-producing glands and tissues that coordinate to maintain homeostasis. Unlike exocrine glands (which secrete into ducts), endocrine glands are ductless and release hormones directly into the bloodstream for transport to distant target tissues.

Hormones are synthesized within specialized cells of these glands through various biochemical pathways, depending on the hormone type. Once released, hormones travel through the blood either freely (water-soluble hormones dissolve in plasma) or bound to carrier proteins (lipid-soluble hormones like steroids and thyroid hormones need protein carriers since they don't dissolve well in blood). Binding to carrier proteins also protects hormones from being broken down too quickly.

Hormone levels are further regulated by metabolism and clearance. The liver modifies hormones chemically, and the kidneys excrete them. The rate of this clearance, combined with the rate of secretion, determines how long a hormone's signal lasts in the body.