The Endocrine System: Overview

Major Control Systems of the Body

The endocrine system is one of the body's two major control systems, interacting with the nervous system to coordinate and integrate the activity of most body cells. It uses hormones—chemical messengers transported in blood—to influence metabolic activities. Endocrine responses are slower but longer lasting than nervous system responses.

• Endocrinology: The study of hormones and endocrine organs.

• Hormones: Long-distance chemical signals that travel in blood to reach target cells.

• Major processes controlled: Reproduction, growth and development, maintenance of electrolyte, water, and nutrient balance, regulation of cellular metabolism and energy balance, mobilization of body defenses.

Comparison of Nervous and Endocrine Systems

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

Endocrine vs. Exocrine Glands

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

• Endocrine glands: Produce hormones; ductless; hormones secreted directly into extracellular fluid. Includes pituitary, thyroid, parathyroid, adrenal, and pineal glands.

• Neuroendocrine organ: Hypothalamus.

• Other organs with endocrine tissue: Pancreas, gonads, placenta, stomach, intestine, heart, kidneys, skin, thymus, bone, adipose.

Hormone Structure and Action

Chemical Classes of Hormones

The chemical structure of a hormone determines its solubility in water, which affects transport, degradation, and receptor interaction.

• Amino acid–based hormones: Includes derivatives, peptides, and proteins; water soluble (except thyroxine); cannot cross plasma membrane.

• Steroid hormones: Synthesized from cholesterol; lipid soluble; can cross plasma membrane; includes gonadal and adrenocortical hormones.

• Eicosanoids: Sometimes considered hormones, but mostly classified as paracrines and autocrines due to localized effects.

Hormone Mechanisms of Action

Hormones act through second messengers or by activating specific genes, depending on their chemical nature and receptor location.

• Water-soluble hormones: Act on plasma membrane receptors; most are coupled via G proteins to second messengers.

• Lipid-soluble hormones: Act on intracellular receptors that directly activate genes; can diffuse across plasma membrane.

Cyclic AMP (cAMP) Second Messenger System

Amino acid–based hormones (except thyroid hormone) exert effects through second-messenger systems, such as cAMP.

1. Hormone (first messenger) binds to receptor.

2. Receptor activates a G protein.

3. G protein activates adenylate cyclase.

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

5. cAMP activates protein kinases that phosphorylate other proteins.

Direct Gene Activation by Lipid-Soluble Hormones

Lipid-soluble steroid hormones and thyroid hormone diffuse into target cells and bind with intracellular receptors, initiating transcription of specific genes.

• Receptor-hormone complex enters nucleus and binds to DNA.

• Binding initiates DNA transcription to produce mRNA.

• mRNA is translated into a specific protein.

Regulation of Hormone Release

Types of Stimuli Causing Hormone Release

Hormone release is controlled by negative feedback mechanisms and triggered by three types of stimuli: humoral, neural, and hormonal.

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

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

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

Hypothalamus and Pituitary Gland

Anatomy and Relationship

The hypothalamus controls release of hormones from the pituitary gland in two different ways. The pituitary has two major lobes: the posterior pituitary (neurohypophysis) stores and secretes neurohormones, while the anterior pituitary (adenohypophysis) manufactures and secretes hormones.

Mechanisms of Hypothalamic Control

• Production of antidiuretic hormone (ADH) and oxytocin (OXT).

• Secretion of regulatory hormones to control activity of the anterior lobe of the pituitary gland.

• Control of sympathetic output to adrenal medulla.

Posterior Pituitary and Hypothalamic Hormones

The posterior pituitary consists of axon terminals of neurons whose cell bodies are in hypothalamic nuclei. It stores and releases oxytocin and antidiuretic hormone (ADH).

• Oxytocin: Stimulates uterine contractions and milk ejection; uses PIP2-calcium second messenger system; acts as neurotransmitter in the brain.

• ADH: Signals kidney tubules to reabsorb more water; high concentrations cause vasoconstriction (vasopressin); release triggered by high blood osmolarity, pain, low blood pressure, and certain drugs; inhibited by alcohol.

Anterior Pituitary Hormones

Summary Table: Pituitary Hormones

The anterior pituitary secretes six peptide or protein hormones, most of which activate target cells via cAMP second-messenger system. Four are tropic hormones that regulate secretion of other hormones.

The Thyroid Gland

Location and Structure

The thyroid gland is a butterfly-shaped organ located on the anterior trachea, just inferior to the larynx. It consists of two lateral lobes connected by an isthmus and contains follicles filled with colloid, which is the precursor for thyroid hormone.

Thyroid Hormone (TH)

TH is the body's major metabolic hormone, produced in two forms: T4 (thyroxine) and T3 (triiodothyronine). It increases basal metabolic rate, regulates tissue growth and development, and is permissive for epinephrine and norepinephrine.

• Synthesis: Involves iodination of thyroglobulin and formation of T3 and T4.

• Transport: Bound to thyroxine-binding globulins (TBGs); T3 is more active than T4.

• Regulation: Negative feedback via TSH and TRH.

Major Effects of Thyroid Hormone

Calcitonin

Calcitonin is produced by parafollicular (C) cells in response to high blood Ca2+ levels. It inhibits osteoclast activity and stimulates Ca2+ uptake into bone matrix.

The Parathyroid Glands

Regulation of Blood Calcium Levels

The parathyroid glands are primary regulators of blood calcium levels. Parathyroid hormone (PTH) is secreted in response to low blood Ca2+ and acts on bones, kidneys, and intestine.

• Stimulates osteoclasts to release Ca2+ from bone.

• Enhances reabsorption of Ca2+ and secretion of phosphate by kidneys.

• Promotes activation of vitamin D for increased Ca2+ absorption in intestine.

The Adrenal Glands

Structure and Function

The adrenal glands are pyramid-shaped organs on the kidneys, consisting of the adrenal cortex (three layers producing corticosteroids) and adrenal medulla (secreting catecholamines).

Adrenal Cortex Hormones

• Mineralocorticoids (e.g., aldosterone): Regulate electrolyte balance, blood volume, and pressure.

• Glucocorticoids (e.g., cortisol): Influence metabolism, resist stressors, regulate blood glucose.

• Gonadocorticoids (androgens): Contribute to sex characteristics and libido.

Adrenal Medulla Hormones

• Catecholamines (epinephrine and norepinephrine): Mediate fight-or-flight response, increase heart rate, blood pressure, and blood glucose.

The Pineal Gland

Melatonin Secretion

The pineal gland secretes melatonin, which regulates sleep-wake cycles and may prevent oxidative damage within cells.

The Pancreas

Structure and Function

The pancreas is a mixed gland with both exocrine and endocrine functions. The endocrine portion consists of pancreatic islets, which contain alpha cells (produce glucagon) and beta cells (produce insulin).

• Glucagon: Raises blood glucose by promoting glycogen breakdown and gluconeogenesis in the liver.

• Insulin: Lowers blood glucose by promoting glucose uptake and storage.

The Gonads and Placenta

Hormone Production

• Ovaries: Produce estrogens, progesterone, and inhibin; regulate reproductive organ maturation and menstrual cycle.

• Testes: Produce testosterone and inhibin; regulate reproductive organ maturation and sperm production.

• Placenta: Temporary endocrine organ during pregnancy; secretes estrogens, progesterone, and hCG.

Hormone Secretion by Other Organs

Selected Examples

• Adipose tissue: Leptin, resistin, adiponectin regulate appetite and insulin sensitivity.

• GI tract: Gastrin, ghrelin, secretin, CCK regulate digestive functions.

• Heart: ANP and BNP decrease blood volume and pressure.

• Kidneys: Erythropoietin stimulates red blood cell production; renin activates renin-angiotensin-aldosterone system.

• Skeleton: Osteocalcin increases insulin production and sensitivity.

• Skin: Cholecalciferol (vitamin D precursor) increases calcium absorption.

• Thymus: Thymosins, thymulin, thymopoietins involved in T lymphocyte development.

Developmental Aspects and Environmental Effects

Endocrine Function Throughout Life

• Most endocrine organs operate well until old age.

• GH, estrogen, testosterone, and TH levels decline with age.

• Glucose tolerance deteriorates with age.

• PTH levels remain constant, but lack of estrogen increases bone vulnerability in older women.

Effects of Environmental Pollutants

• Exposure to pesticides, industrial chemicals, and pollutants disrupts hormone function.

• Sex hormones, thyroid hormone, and glucocorticoids are vulnerable to environmental effects.