Human Endocrine System

The human endocrine system plays a central role in regulating critical physiological processes in the body using chemical messengers called hormones. Hormones are released from endocrine glands, the brain, and other tissues like the heart (atrial natriuretic peptide), kidneys (erythropoietin), and adipose tissue (leptin). Endocrine hormones travel through the bloodstream to target cells throughout the body where they bind to specific protein receptors and cause specific physiological effects. The endocrine system works in tandem with the nervous system to mediate growth, metabolism, reproduction, and behavior.

Glands

The human endocrine system consists of a number of organs and glands located throughout the body. These include the hypothalamus, pituitary gland, pineal gland, thyroid gland, parathyroid gland, adrenal glands, pancreas, ovaries, and testes.

• Hypothalamus: A brain structure linking the nervous and endocrine systems, the hypothalamus plays an important role in regulating the endocrine system. It produces hormones that stimulate or inhibit the release of other hormones from the pituitary gland.
• Pituitary Gland: Often called the “master gland,” this pea-sized structure located at the base of the brain secretes hormones that influence a variety of bodily functions.
• Pineal Gland: A small endocrine gland located in the center of the brain, the pineal gland secretes melatonin to maintain the body's internal clock—the circadian rhythm.
• Thyroid: A butterfly-shaped organ located in the neck that secretes hormones involved in metabolism and growth. The thyroid gland produces thyroxine (T4) and triiodothyronine (T3), which are responsible for regulating the body's metabolism, growth and development, and body temperature.
• Parathyroid Glands: Four small glands located on each side of the thyroid gland. The parathyroid glands secrete parathyroid hormone, which regulates calcium levels in the blood.
• Adrenal Glands: Two triangular-shaped glands positioned above the kidneys. Each gland has an outer cortex and inner medulla. The cortex produces corticosteroids, including cortisol, vital for metabolism and stress responses, and the medulla generates catecholamines, such as epinephrine, essential in acute stress reactions.
• Pancreas: An organ situated behind the stomach that secretes insulin and glucagon, the pancreas helps regulate blood sugar levels.
• Ovaries: Two small glands located in the female pelvis, the ovaries produce female sex hormones, including estrogen and progesterone.
• Testes: Two small organs located in the male scrotum, the testes produce several hormones including testosterone, inhibin B, and anti-mullerian hormone.

Hormones

Hormones (from the Greek horman, meaning “to excite”) are complex molecules that help regulate various biological processes.

Chemical Classification

Hormones are commonly classified by their chemical structure as amino acid-based (amines, peptides, and proteins) or lipid-based (steroids and eicosanoids).

Amino Acid-Based

• Amines: Simple hormones derived from the amino acids tyrosine or tryptophan. They are either produced and released directly into the bloodstream or stored in secretory granules for rapid release into the blood in response to a stimulus. This class includes both water-soluble and lipid-soluble subtypes.
  • Catecholamines and Indoleamines: Water-soluble amines, catecholamines and indoleamines are produced in the adrenal gland and pineal gland. Examples include epinephrine and melatonin.
  • Iodothyronines (Thyroid Hormones): Lipid-soluble amines, iodothyronines are produced in the thyroid. They must be bound to proteins to transit the blood. Examples include triiodothyronine and thyroxine.

• Peptides and Proteins: Complex, water-soluble hormones composed of chains of amino acids. Peptides and proteins are the most common type of hormone.
  • Peptides: Peptides are built from short amino acid chains. Examples include oxytocin and parathyroid hormone.
  • Proteins: Built from long amino acid chains. Examples include insulin and human growth hormone.
  • Glycoproteins: Composed of proteins and carbohydrates. Examples include follicle-stimulating hormone (FSH), luteinizing hormone (LH), and thyroid-stimulating hormone (TSH).

Lipid-Based

• Steroids: Steroids are lipid-soluble hormones derived from cholesterol and produced in the gonads (testes or ovaries) and adrenal glands. Examples include cortisol, testosterone, and estrogen.
• Eicosanoids: Eicosanoids are lipid-derived hormones that (almost always) act locally. Rather than circulating in the blood to target cells, eicosanoids primarily act near the location of synthesis. Despite this, they can also operate as endocrine regulators, indirectly impacting the activities of cells located far away. Examples include prostaglandins, thromboxanes, leukotrienes, and lipoxins.

Communication Systems

Hormones utilize distinct pathways from their synthesis site to their action site. Endocrine signaling involves hormone transport through the bloodstream to distant target cells, exemplified by insulin's role in regulating body-wide blood glucose levels. Paracrine signaling happens when paracrine factors are released into the extracellular space, affecting nearby cells within the same tissue, as observed in growth factor actions during tissue repair. Autocrine signaling involves hormones acting on the cells that secrete them, common in immune responses. Finally, intracrine signaling takes place entirely within the originating cell, crucial in some gene expression processes.

Action Pathways

There are two primary pathways by which hormones influence target cells. Second-messenger systems rely on cell surface receptors and usually produce direct changes in the function of the target cell. Direct gene activation occurs when hormones bind to intracellular receptors. The hormone-receptor complex interacts with short sections of DNA, called hormone response elements (HREs), stimulating the expression of specific genes that contain the blueprints for building desired proteins and enzymes. The ultimate effect depends on the pathway.

• Second-Messenger System: Most amino acid-based hormones are water-soluble (hydrophilic) and cannot pass through a target cell’s plasma membrane. Because of this, they affect target cells by binding to a protein receptor on the surface cell’s surface. Once the hormone (first messenger) binds to a receptor, that receptor activates an enzyme that creates signaling molecules (secondary messengers), triggering a cascade of enzyme activations that amplify the response and propagate it throughout the cell.
• Direct Gene Activation: Steroid hormones and thyroid-based amines are lipophilic and can diffuse through cell membranes to bind with specific intracellular receptors in the cytoplasm or nucleus. Once bound, the hormone-receptor complex enters the nucleus, binds to DNA, and activates gene expression. The end-products of these expressed genes, often enzymes, are the main drivers of the biologic effects of lipophilic hormones.

System Regulation

Endocrine system activity is carefully regulated through three primary control methods: humoral control, hormonal control, and nervous system control. These control systems employ negative feedback loops that provide stability and tight regulation of hormonal effects on homeostasis. Positive feedback loops also exist but are very rare in the endocrine system. Most hormones are regulated by more than one of these systems at the same time.

Humoral Control

Humoral controls directly regulate the release of hormones based on the current blood concentration of certain substances. For instance, blood glucose is a stimulus for the pancreas to release insulin. As blood glucose increases, more insulin is secreted. Insulin lowers the amount of glucose in the blood by promoting its uptake into cells to make energy and by increasing glucose storage in the liver. Decreasing blood glucose in turn inhibits the release of insulin so blood sugar doesn’t continue to fall. At the same time, declining blood sugar triggers the release of glucagon from the pancreas. Glucagon exerts the opposite effect by stimulating the liver to release glucose into the bloodstream to raise and maintain blood glucose levels. This completes the loop and allows the body to maintain blood sugar levels within a narrow, consistent range even when large amounts of glucose are entering the bloodstream, such as after eating.

Hormonal Control

Tropic hormones control the production and release of other hormones. Most hormones produced and secreted by the pituitary gland are considered tropic hormones. For example, the pituitary gland secretes gonadotropins, such as follicle-stimulating hormone (FSH) and luteinizing hormone (LH), which stimulate the production of sex hormones like testosterone, estrogen, and progesterone in the gonads. These exert their own effects as steroid hormones, but the increasing concentration of sex hormones in the blood completes another negative feedback loop by suppressing further release of LH and FSH.

Some tropic hormones can also directly inhibit the release of other hormones. Somatostatin, produced by delta cells found throughout the digestive system, is one such hormone. It inhibits insulin and glucagon secretion from the pancreas and limits the release of other gastrointestinal hormones such as gastrin and histamine.

Neural Control

The nervous system influences the endocrine system through several mechanisms. In some instances, nerve signals can stimulate hormone release from target glands, such as the sympathetic nervous system stimulating epinephrine release from the adrenal glands.

Neuroendocrine hormones, produced in the brain's hypothalamus and pituitary gland, include "releasing" hormones, which are produced by hypothalamic neurons (nerve cells). They stimulate the pituitary gland to release additional hormones. Examples include gonadotropin-releasing hormone (GnRH), growth hormone-releasing hormone (GHRH), and thyroid-releasing hormone (TRH), which prompt the pituitary to release gonadotropins, growth hormone, and thyroid-stimulating hormone (TSH), respectively. Other neuroendocrine hormones, namely oxytocin and vasopressin, are released directly into the bloodstream from the pituitary gland.

Neuroendocrine hormones play a central role in mediating the negative feedback control of the hormones they cause to be released. The releasing hormones are sensitive to increasing concentrations of the end-products of the signal cascade they initiate. GnRH, for instance, stimulates the release of LH and FSH, which act on the gonads to increase production of sex hormones such as testosterone and estrogen. As levels of these sex hormones in the blood increase, they suppress further GnRH release from the hypothalamus, completing the negative feedback loop.

Endocrine vs. Nervous Systems

The endocrine and nervous systems both regulate and coordinate body functions. The nervous system exerts near instantaneous and short-lived control of specific target cells via electrical and chemical signals relayed along direct neuron chain connections, where one neuron passes signals directly to the next without any detours or intermediary stops. In contrast, the endocrine system, lacking direct anatomical connections, diffuses hormones broadly, affecting target cells with specific receptors. Endocrine signals exert slower but longer-lasting effects.

Additional resources:

• Introduction to the Endocrine System by the National Cancer Institute
• Human Endocrine System by Britannica

Contributors:

• Randall Higgins, PharmD

Reviewers:

• Ari Magill, MD
• Joanne Jarrett, MD

Published: January 11, 2024