Table of Contents
Overview: How the Nervous and Endocrine Systems Work Together
The nervous and endocrine systems are two major control systems in animals (especially well-studied in vertebrates and humans). They are not independent: many important body functions are only possible because these two systems are tightly coupled.
In this chapter, the focus is on:
- How nerve cells influence hormone-producing cells
- How hormones influence the nervous system, including the brain
- Special “interface organs” and cell types that link both systems
- Typical examples of “neuroendocrine control loops” (feedback circuits involving both systems)
General properties of hormones and the endocrine system, as well as basic nervous system structure and function, are discussed in other chapters and are not repeated here.
Two Control Systems with Different Strengths
The nervous and endocrine systems differ in their mode and speed of action:
- Nervous system:
- Transmission via action potentials and neurotransmitters
- Very fast (milliseconds to seconds)
- Highly localized (specific synapses)
- Endocrine system:
- Transmission via hormones in the blood or tissue fluid
- Slower (seconds to hours, sometimes days)
- Often widespread effects (throughout the body)
Coupling both systems allows organisms to:
- Translate fast, brief nervous signals into longer-lasting hormonal actions
- Adjust hormone secretion to environmental stimuli detected by the nervous system
- Allow hormones to modulate mood, attention, and behavior by acting on the brain
Neurosecretory Cells: Nerve Cells That Act Like Endocrine Cells
A key element in coupling is the neurosecretory cell:
- Structurally a neuron (has cell body, axon, dendrites)
- Produces hormones or hormone-like substances
- Releases these substances into the blood or interstitial fluid, not only into synaptic clefts
Thus, neurosecretory cells combine:
- Nervous function (electrical excitation, synaptic integration)
- Endocrine function (hormone synthesis and secretion)
Examples:
- In vertebrates, many neurosecretory cells are located in the hypothalamus of the brain and control the pituitary gland.
- In invertebrates (e.g., insects), neurosecretory cells in the brain release hormones that control molting, metamorphosis, and reproduction.
The Hypothalamus–Pituitary Axis: Central Interface in Vertebrates
In vertebrates and humans, the main coupling structure between nervous and endocrine systems is the hypothalamus–pituitary axis (often abbreviated HPA for “hypothalamic–pituitary axis” in a general sense; more specific axes have additional names).
Hypothalamus: Brain Region with Endocrine Control Functions
The hypothalamus is a small but vital brain region that:
- Receives sensory information from almost all parts of the nervous system:
- Internal state (e.g., blood temperature, osmolarity, blood glucose level)
- External information (e.g., light–dark cycle via the eyes, stress signals from higher brain centers)
- Integrates this information
- In response, neurosecretory cells of the hypothalamus release:
- Hormones into the blood
- Or signals into special blood vessels leading to the pituitary
- Or neurohormones transported along axons to the posterior pituitary
The hypothalamus thus transforms neural signals into hormonal signals.
Pituitary Gland: “Master Gland” Under Neural Control
The pituitary gland (hypophysis) is directly connected to the hypothalamus and has two major parts with different kinds of coupling:
Posterior Pituitary (Neurohypophysis)
- Structurally an extension of the hypothalamus
- Contains the axon endings of hypothalamic neurosecretory cells
- Hypothalamic hormones (e.g., oxytocin, vasopressin/ADH) are:
- Synthesized in neuron cell bodies in the hypothalamus
- Transported along axons
- Released from axon terminals into the blood in the posterior pituitary
Here, the link is direct neurosecretion: action potentials in hypothalamic neurons trigger hormone release into the bloodstream.
Anterior Pituitary (Adenohypophysis)
- True endocrine tissue
- Its hormone-producing cells are not neurons
- Controlled by hypothalamic hormones that reach it through a special portal blood vessel system (hypothalamo–hypophyseal portal system)
Sequence:
- Neurosecretory cells in the hypothalamus release releasing or inhibiting hormones into small local capillaries.
- These blood vessels run directly to the anterior pituitary.
- The hypothalamic hormones regulate secretion of anterior pituitary hormones.
Thus, short neural signals in hypothalamic neurons lead to longer-lasting hormone secretion by anterior pituitary cells.
Example Hormone Axes
Anterior pituitary hormones often control other endocrine organs. This leads to multi-step control chains called axes:
- Hypothalamus → Pituitary → Peripheral endocrine gland → Target tissues
Examples (details of the individual hormones are handled in other chapters):
- Stress axis (HPA axis in a narrow sense):
- Hypothalamus: corticotropin-releasing hormone (CRH)
- Pituitary: adrenocorticotropic hormone (ACTH)
- Adrenal cortex: glucocorticoids (e.g., cortisol)
- Thyroid axis (HPT axis):
- Hypothalamus: thyrotropin-releasing hormone (TRH)
- Pituitary: thyroid-stimulating hormone (TSH)
- Thyroid gland: thyroid hormones
- Gonadal axis (HPG axis):
- Hypothalamus: gonadotropin-releasing hormone (GnRH)
- Pituitary: LH (luteinizing hormone) and FSH (follicle-stimulating hormone)
- Gonads: sex hormones
In all these axes, the hypothalamus and pituitary link nervous input to hormone output.
Feedback Loops Involving Nervous and Endocrine Systems
The coupling is not one-way. Hormones produced under neural control can, in turn, influence the nervous system, including their own control centers. This organization usually forms feedback loops.
Negative Feedback
Most hormone axes are controlled by negative feedback:
- Rising levels of a hormone reduce further secretion.
- This stabilizes the internal environment.
Typical scheme:
- Hypothalamus releases a releasing hormone.
- Pituitary secretes a tropic hormone.
- Peripheral endocrine gland produces a peripheral hormone.
- Peripheral hormone:
- Inhibits hypothalamus (less releasing hormone)
- Inhibits pituitary (less tropic hormone)
As a result, hormone concentrations oscillate around an appropriate level instead of rising without limit.
Neural signals (e.g., stress, fear, changes in temperature) can temporarily override or adjust this set point, leading to increased or decreased hormone secretion.
Positive Feedback (Rare)
In some special cases, hormone secretion is increased by positive feedback:
- A hormone stimulates processes that further increase its own secretion.
- This is usually short-lived and ends through external changes or exhaustion of resources.
Positive feedback involving neuroendocrine coupling is less common but occurs in certain reproductive processes (details in reproductive chapters).
Hormonal Modulation of Nervous System Activity
Just as nerves control hormone secretion, hormones strongly influence the nervous system.
Hormones Acting on the Brain
Many hormones can cross the blood–brain barrier or act on specific brain regions:
- Metabolic and appetite hormones influence:
- Hunger and satiety centers
- Reward systems
- Stress hormones affect:
- Vigilance and attention
- Fear and anxiety circuits
- Sex hormones modulate:
- Sexual behavior
- Aggression and parental behavior
- Thyroid hormones influence:
- Brain development
- General excitability and mental activity
Thus, hormones are important chemical messengers for:
- Long-term modulation of mood and behavior
- Developmental processes in the nervous system
- Adjustment of the brain’s response to stimuli
Neurotransmitters vs. Neurohormones
Some substances can function both as neurotransmitters and hormones, depending on where and how they are released:
- As neurotransmitters:
- Released into synaptic clefts
- Act locally and quickly on postsynaptic cells
- As neurohormones:
- Released into the blood
- Act more slowly on distant cells and organs
This dual role further blurs the boundary between nervous and endocrine signaling and is central to their coupling.
Autonomic Nervous System and Endocrine Response
The autonomic (vegetative) nervous system is another important interface:
- It regulates involuntary functions (heart rate, digestion, blood vessel diameter, etc.).
- It directly innervates some endocrine glands and influences hormone release.
Example: Sympathetic System and Adrenal Medulla
The sympathetic nervous system activates the adrenal medulla (the inner part of the adrenal gland):
- Sympathetic preganglionic neurons send action potentials to the adrenal medulla.
- Cells of the adrenal medulla (modified neurons) release catecholamines (e.g., adrenaline/epinephrine) into the blood.
- These hormones prepare the body for “fight or flight”:
- Increased heart rate
- Mobilization of energy reserves
- Redirected blood flow (e.g., to muscles)
Here, a direct neural signal leads to a rapid hormonal stress response that reaches the whole body.
Temporal Coordination: Short-Term vs. Long-Term Control
Coupling of nervous and endocrine systems makes it possible to coordinate body functions over different time scales:
- Very fast responses (seconds):
- Purely neural or mixed neuro–hormonal (e.g., acute stress response via sympathetic nerves and adrenal medulla)
- Intermediate responses (minutes to hours):
- Hypothalamus–pituitary–peripheral gland axes
- Adaptation to changes in environment (temperature, food intake, etc.)
- Long-term responses (days to years):
- Growth, sexual maturation, seasonal reproduction
- Long-term stress adaptation
- Biological rhythms (sleep–wake cycle, annual cycles)
Neural signals initiate or adjust endocrine programs; hormones, in turn, shape how the nervous system reacts over longer periods.
Biological Rhythms and Clock Systems
Certain endocrine functions are organized in rhythms (e.g., daily or annual). The coupling with the nervous system is essential here:
- Light information from the eyes reaches specific brain regions that control biological clocks.
- These clock centers regulate:
- Hypothalamic activity
- Hormone release patterns (e.g., daily rhythm of certain hormones)
Consequences:
- Many hormones show circadian rhythms (approximately 24-hour cycles).
- Behaviors such as sleep–wake cycles, feeding times, and reproductive behaviors are synchronized to environmental cycles through neuroendocrine coupling.
Integration of Environmental Signals, Internal State, and Behavior
By tightly linking the nervous and endocrine systems, organisms can align:
- External stimuli (e.g., light–dark changes, presence of predators or mates)
- Internal status (energy reserves, hydration, reproductive readiness)
- Appropriate physiological responses and behaviors
Key aspects of this integration:
- Nervous system:
- Detects and interprets complex environmental and internal signals
- Initiates rapid, targeted responses
- Informs endocrine centers (especially the hypothalamus)
- Endocrine system:
- Converts these signals into coordinated body-wide changes
- Stabilizes the internal environment (homeostasis)
- Supports long-term adjustments and developmental programs
This coupling is essential for survival: it ensures that organs, tissues, and behavior are tuned to each other and to the changing environment.