The Endocrine System: Overview and Mechanisms (Chapter 16, Part A)

The Endocrine System

Endocrine System Overview

The endocrine system works alongside the nervous system to coordinate and integrate the activity of body cells. It primarily influences metabolic activities through hormones transported in the blood. Endocrine responses are slower but longer-lasting than those of the nervous system.

• Endocrine system: Acts with the nervous system to regulate body functions.

• Hormones: Chemical messengers secreted into the blood, affecting distant target cells.

• Endocrinology: The study of hormones and endocrine organs.

Comparison of Nervous and Endocrine Systems

The nervous and endocrine systems differ in their signaling mechanisms and effects.

Nervous System	Endocrine System
Initiates responses rapidly	Initiates responses slowly
Short-duration responses	Long-duration responses
Acts via action potentials and neurotransmitters	Acts via hormones released into the blood
Acts at specific locations (axon pathways)	Acts at diffuse locations (targets anywhere blood reaches)
Neurotransmitters act over short distances	Hormones act over long distances

Functions of the Endocrine System

• Reproduction

• Growth and development

• Maintenance of electrolyte, water, and nutrient balance

• Regulation of cellular metabolism and energy balance

• Mobilization of body defenses

Endocrine vs. Exocrine Glands

• Exocrine glands: Produce nonhormonal substances (e.g., sweat, saliva); have ducts to carry secretions to membrane surfaces.

• Endocrine glands: Produce hormones; lack ducts.

Major Endocrine Organs

• Pituitary gland

• Thyroid gland

• Parathyroid glands

• Adrenal glands

• Pineal gland

• Hypothalamus: Considered a neuroendocrine organ

• Some organs have both exocrine and endocrine functions (e.g., pancreas, gonads, placenta)

• Other hormone-producing tissues: adipose cells, thymus, cells in the small intestine, stomach, kidneys, and heart

Location of Selected Endocrine Organs

Endocrine organs are distributed throughout the body, including the brain, neck, abdomen, and pelvis.

Chemical Messengers of the Endocrine System

• Hormones: Long-distance chemical signals in blood or lymph

• Autocrines: Chemicals that exert effects on the same cells that secrete them

• Paracrines: Chemicals that affect nearby cells other than those that secrete them

• Autocrines and paracrines are local messengers, not considered part of the endocrine system

Classes of Hormones

• Amino acid-based hormones: Includes amino acid derivatives, peptides, and proteins

• Steroids: Synthesized from cholesterol (e.g., gonadal and adrenocortical hormones)

• Eicosanoids: Sometimes considered hormones, but mostly classified as paracrines

Target Cells and Hormone Action

• Only cells with specific receptors for a hormone are affected (target cells)

• Hormones alter target cell activity by:

  • Altering plasma membrane permeability or membrane potential

  • Stimulating synthesis of enzymes or proteins

  • Activating or deactivating enzymes

  • Inducing secretory activity

  • Stimulating mitosis

Mechanisms of Hormone Action

• Water-soluble hormones (all amino acid-based except thyroid hormone):

  • Act on plasma membrane receptors

  • Act via G protein second messengers

  • Cannot enter the cell

• Lipid-soluble hormones (steroid and thyroid hormones):

  • Act on intracellular receptors that directly activate genes

  • Can enter the cell

Hormone Signaling Mechanisms

Plasma Membrane Receptors and Second-Messenger Systems

Amino acid-based hormones (except thyroid hormone) exert effects through second-messenger systems. Two main systems:

• Cyclic AMP (cAMP)

• PIP2-calcium

Cyclic AMP (cAMP) Signaling Mechanism

1. Hormone (first messenger) binds to receptor

2. Receptor activates a G protein

3. G protein activates or inhibits adenylate cyclase

4. Adenylate cyclase converts ATP to cAMP (second messenger)

5. cAMP activates protein kinases that phosphorylate other proteins

• Phosphorylated proteins are activated or inactivated

• cAMP is rapidly degraded by phosphodiesterase, stopping the cascade

• Cascades have a large amplification effect

PIP2-Calcium Signaling Mechanism

• Hormone-activated G protein activates phospholipase C

• Phospholipase C splits PIP2 into two second messengers:

  • Diacylglycerol (DAG): Activates protein kinases

  • Inositol triphosphate (IP3): Causes Ca2+ release from intracellular stores

• Calcium ions act as another second messenger, binding to calmodulin and activating enzymes that amplify the cellular response

Other Signaling Mechanisms

• cGMP (cyclic guanosine monophosphate): Second messenger for selected hormones

• Some hormones (e.g., insulin) work without second messengers, using tyrosine kinase receptors

Intracellular Receptors and Direct Gene Activation

• Lipid-soluble steroid and thyroid hormones diffuse into target cells and bind with intracellular receptors

• Receptor-hormone complex enters the nucleus and binds to specific DNA regions

• Initiates DNA transcription to produce mRNA

• mRNA is translated into specific proteins with various functions (e.g., metabolic activities, structural purposes)

Hormone Regulation and Target Cell Specificity

Hormone Release

• Blood levels of hormones are controlled by negative feedback systems

• Increased hormone effects on target organs can inhibit further release

• Hormone release is triggered by:

  • Endocrine gland stimuli

  • Nervous system modulation

Types of Endocrine Gland Stimuli

• Humoral stimuli: Changing blood levels of ions/nutrients directly stimulate hormone secretion (e.g., low Ca2+ stimulates parathyroid hormone release)

• Neural stimuli: Nerve fibers stimulate hormone release (e.g., sympathetic nervous system stimulates adrenal medulla)

• Hormonal stimuli: Hormones stimulate other endocrine organs to release their hormones (e.g., hypothalamic hormones stimulate anterior pituitary)

Target Cell Specificity

• Target cells must have specific receptors for a hormone

• Activation depends on:

  1. Blood levels of hormone

  2. Number of receptors on/in target cell

  3. Affinity (strength) of binding between receptor and hormone

• Up-regulation: Target cells form more receptors in response to low hormone levels

• Down-regulation: Target cells lose receptors in response to high hormone levels

Half-Life, Onset, and Duration of Hormone Activity

• Hormones circulate in blood either free or bound to plasma proteins

• Concentration reflects rate of release and speed of inactivation/removal

• Removal by degrading enzymes, kidneys, or liver

• Half-life: Time required for hormone level to decrease by half (varies by hormone)

• Response times vary (immediate to days); duration usually limited (seconds to hours)

• Half-life, onset, and duration depend on whether hormone is water- or lipid-soluble

Lipid-Soluble Hormones	Water-Soluble Hormones
All steroid hormones and thyroid hormone	All amino acid-based hormones except thyroid hormone
Adrenal cortex, gonads, thyroid gland	All other endocrine glands
Bound to plasma proteins	Usually free in plasma
Long half-life (must be metabolized by liver)	Short half-life (removed by kidneys)
Inside cell	On plasma membrane
Activates genes, causing synthesis of new proteins	Usually acts through second-messenger systems

Interaction of Hormones at Target Cells

• Permissiveness: One hormone cannot exert its effects without another hormone being present (e.g., reproductive hormones need thyroid hormone)

• Synergism: More than one hormone produces the same effects, causing amplification (e.g., glucagon and epinephrine both cause liver to release glucose)

• Antagonism: One or more hormones oppose the action of another (e.g., insulin and glucagon)