Endocrine system

Endocrine system (base definition)

A system made up of endocrine cells and tissues that produce about 30 different hormones that control and coordinate body processes like

• growth and development

• reproduction

• regulation of cell metabolism and energy balance

• regulation of body water content and levels of electrolytes and organic nutrients

• mobilization of body defenses

Signal differences between endocrine and nervous system (Type of signal, signaling speed, duration of signal, chemical signaling, and signal targeting)

Endocrine: chemical, slow, long, long range, broad net

Nervous: electrochemical, fast, short, short range/synaptic, specific

Similarities between endocrine and nervous system

• rely on the release of chemicals that bind to specific receptors on their target cells.

• share many chemical messengers

• regulated by negative feedback control mechanisms

• preserve homeostasis by coordinating and regulating the activities of other cells, tissues, organs, and systems.

Hormones (definition)

chemical messengers (endocrine signals) released by a signaling cell and received by a receptor cell, that relays info and instructions between cells

Intercellular communication (def) and mechanisms

def - chemicals transmitted between cells

Mechanisms

Direct communication: Exchange of ions and molecules between adjacent cells across gap junctions

• non-hormonal

• occurs between 2 cells of the same type

• highly specialized and relatively rare

Paracrine communication: chemical signals transfer info from cell to cell within a single tissue.

Endocrine communication: Endocrine cells release hormones that are transported in the blood to distant sites or organs. (Also often alters metabolic activities of organs)

Autocrine communication: Messages affect the same cells that secrete them.

• the chemicals are called autocrines

Synaptic communication: nervous system

Target cells

has receptors needed to bind and read hormonal messages

What hormones do

• change types, quantities, or activities of enzymes and structural proteins in target cells

• can alter metabolic activities of multiple tissues and organs at the same time

• affect long term processes like growth and development.

Endocrine system (more specifically)

• includes all endocrine cells and tissues that produce hormones or paracrines

• endocrine organs are scattered through the body

• endocrine cells release secretions into extracellular fluid in contrast to exocrine cells which release secretions onto epithelial cells through ducts, usually outside the body.

3 classes of hormones

1. amino acid derivatives

2. peptide derivatives

3. lipid derivatives

Amino acid derivatives

Also known as biogenic amines

• small molecules structurally related to amino acids

Derivatives of tyrosine: thyroid hormones and catecholamines (epinephrine, norepinephrine, and dopamine)

Derivatives of tryptophan: serotonin and melatonin

Peptide derivatives

• chains of amino acids

• most are synthesized and prohormones which are inactive molecules converted to active hormones before or after they are secreted

• glycoproteins: proteins more than 200 amino acids long that have carbohydrate side chains

• small proteins: 51-198 amino acids

• short polypeptides: 9 amino acids long

• includes all hormones secreted by hypothalamus, heart, thymus, digestive tract, pancreas, posterior lobe of the pituitary gland

Lipid derivatives

• insoluble in water

• bound to specific transport proteins in the plasma

• remain in circulation longer than peptide hormones.

Types

Eicosanoids: derived from arachidonic acid, a 20-carbon fatty acid

• paracrines that coordinate cellular activities and affect enzymatic processes (such as blood clotting)

• some eicosanoids, like leukotrienes, have secondary roles as hormones

• prostaglandins coordinate local cellular activities

Steroid hormones: derived from cholesterol

• androgens from testes in men

• estrogens and progesterone from ovaries in women

• corticosteroids from adrenal cortex

• calcitriol from kidneys

Transport and Inactivation of hormone

• may circulate freely or travel bound to special carrier proteins

• free hormones are active but labile; bound hormones are inactive but stable.

• free hormones active for less than 1 hour and inactivate when: diffuse out of blood stream and bind to target cells, absorbed or broken down by enzymes or interstitial fluid.

• thyroid and steroid hormones remain functional much longer; more than 99% attach to special transport proteins, and equilibrium exists between free and bound forms.

Binding of a hormone may…

• alter genetic activity (gene expression), alter rate of protein synthesis, and change membrane permeability

(Hormone specificity is determined by the receptors on the target cell.)

Soluble hormone signaling

Intramembrane signaling: external signals received on outside of cell.

• Ex. Insulin, Adrenaline, Wnt, epidermal growth factor (EGF)

Steroid hormone signaling

Cytoplasmic receptors: (hydrophobic) Signaling in the cell.

• Ex. Estrogen, testosterone, cortisol.

Hormone receptors

• a protein molecule to which a particular molecule binds strongly

• receptor ligand interaction —> hormone specificity

Down regulation vs Up regulation

Down: cell decreases sensitivity by removing receptors when hormone levels are high

Up: cell increases sensitivity by adding receptors when hormone levels are low

Second messenger

intermediary molecule that transmits a hormone signal within the cell due to hormone-receptor interaction. Often the measure of hormone activity in cells.

G-protein

Enzyme complex coupled to membrane receptor

• binds GTP to activate

• involved in link between 1st and 2nd messenger

• hydrolyzes back to GDP

G protein and cAMP

1. activated G protein activates adenylate cyclase

2. This converts ATP to cAMP

3. cAMP functions as a second messenger

4. Generally, cAMP activates kinases that phosphorylate proteins

Increase cAMP is usually short-lived

• phosphodieterase (PDE) converts cAMP to AMP which can be turned into ATP

Intracellular receptors

Bind in the cytoplasm and are transported into the nucleus (Steroid hormone signaling)

• can turn on or off genes on DNA strand

• thyroid hormones may bind to mitochondria to increase ATP production

Hormone secretion

Mainly controlled by negative feedback

• Stimulus triggers production of hormone that reduces intensity of the stimulus

Triggered by:

• Humoral stimuli: change in extracellular fluid. Heart, pancreas, parathyroid gland, and digestive tract

• Hormonal stimuli: arrival/removal of hormone

• Neural stimuli: neurotransmitters. Hypothalamus provides highest control.

Pituitary gland

• releases 9 important peptide hormones.

• binds to extracellular receptors

• uses cAMP as a second messenger

Hypothalamus

regulates function of pituitary gland

1. synthesizes ADH and OXT and transports them to posterior pituitary gland for release

2. secretes regulatory hormones that control secretory activity of anterior pituitary gland

3. contains autonomic centers that exert direct control over adrenal medulla

Portal vessels

the entire complex of blood vessels that link two capillary networks

• typically artery-capillaries-vein

• Hypophyseal portal system: Ensures that regulatory hormones reach cells in anterior pituitary before entering general circulation.

Hypothalamus (anterior lobe of pituitary)

• Releasing Hormone (RH) - stimulates synthesis

• Inhibiting Hormone (IH) - prevents synthesis

• Tropic hormones “turn on” other endocrine glands or regulate functions of other organs

• rate of secretion is controlled by negative feedback

All 7 hormones from the anterior lobe of the pituitary are soluble, bind to extracellular receptors, and all use cAMP as a second messenger. TSH, ACTH, FSH, LH follows this typical regulatory pattern.

PRL and GH follow the atypical patterns of regulation.

Growth Hormone (GH) stimulates:

• liver cells to release somatomedins that stimulate tissue growth and cause skeletal muscle fibers and other cells to increase uptake of amino acids

• stem cells in epithelia and connective tissues to divide

• breakdown of triglycerides in adipocytes which lead to glucose-sparing effect

• breakdown of glycogen by liver cells causing diabetogenic effect

Pars intermedia

secretes melanocyte-stimulating hormone (MSH)

• stimulates melanin production

• virtually non-functional in adults except in pregnant women and those with certain diseases.

The pars intermedia lies between the anterior and posterior lobe of the the pituitary gland

Hypothalamus (posterior lobe of pituitary)

• contains unmyelinated axons

• supra-optic (OXT) and paraventricular nuclei (ADH) manufacture

Antidiuretic Hormone: ADH or Vasopressin

• released in response to increased [solute] in blood

• stimulates kidneys to retain water, decrease urination

Oxytocin: OXT.

• stimulates contraction of uterus during labor

• promotes ejection of milk after delivery

Thyroid gland

• lies inferior to thyroid cartilage of larynx

• consists of 2 lobes connected by narrow isthmus

Thyroid follicles

• hollow spheres lined by cuboidal epithelium

• surrounded by capillaries

• cells absorb iodide ions (I^-) from blood

• follicle cavity contains viscous colloid

• C (clear) cells, or parafollicular cells

Thyroglobulin

• globular protein synthesized by follicle cells

• secreted into colloid of thyroid follicles

• contain the amino acid tyrosine which is the building block of thyroid hormones

Thyroid hormones

• Thyroxine (T₄), or tetraiodothyronine: contains 4 iodine atoms

• Triiodothyronine (T₃): contains 3 iodine atoms

Thyroid-stimulating hormones (TSH)

• absence causes thyroid follicles to become inactive. Neither synthesis nor secretion occurs

• Binds to plasma membrane receptors. Activates key enzymes in thyroid hormone production.

Thyroid hormones activate genes involved in glycolysis and ATP production —> calorigenic effect

• increased energy consumption and heat generation of cells

• responsible for strong, immediate, and short-lived increase rate of cellular metabolism.

Effects of thyroid hormones (AIMSIES)

• Accelerate turnover of minerals in bone

• Increase heart rate and force of contraction

• Maintain normal sensitivity of respiratory centers to oxygen and carbon dioxide concentrations

• Stimulate red blood cell formation

• Increase sensitivity to sympathetic stimulation

• Elevate oxygen and energy consumption; in children, may cause rise in body temp.

• Stimulate activity in other endocrine tissues

In children, essential to normal development of skeletal, muscular, and nervous systems

C cells

produces calcitonin (CT)

• helps regulate concentrations of Ca²⁺ in body fluids

• Stimulates Ca²⁺ secretion by kidneys

• Prevents Ca²⁺ absorption by digestive tract

Parathyroid glands

• 2 pairs

• embedded in posterior surface of thyroid gland

• altogether, the 4 glands weigh 1.6g

Parathyroid hormone

PTH

• secreted by parathyroid (principal) cells in response to low concentrations of Ca²⁺ in blood

• antagonist for calcitonin

Major effects of PTH

• stimulates osteoclasts (through osteoblast secretion of RANKL) which accelerates mineral turnover and Ca²⁺ release

• Enhances reabsorption of Ca²⁺ by kidneys, reducing urinary losses which stimulates formation and secretion of calcitriol by kidneys

Adrenal glands

• lie along superior border of each kidney

superficial adrenal cortex:

• store lipids, especially cholesterol and fatty acids

• manufactures steroid hormones (corticosteroids)

Inner adrenal medulla:

• secretory activity controlled by sympathetic division of ANS

• produces epinephrine and norepinephrine (catecholamines)

Pineal gland

Lies in posterior portion of roof of 3rd ventricle and contains pinealocytes:

• pinealocytes synthesize hormone melatonin

Functions of melatonin:

• influence circadian rhythms

• inhibit reproductive functions

• protect against damage by free radicals

Pancreas

• large gland

• lies in loop between inferior border of stomach and proximal portion of small intestine

• mostly retroperitoneal

Exocrine functions of pancreas

• consists of clusters of gland cells called pancreatic acini and their attached ducts

• takes up roughly 99% of pancreatic volume

• gland and duct cells secrete alkaline, enzyme-rich fluid which then passes through a network of ducts to lumen of digestive tract

Endocrine functions of pancreas

Consists of cells that form clusters known as pancreatic islets (islets of Langerhans)

• Alpha cells produce glucagon

• Beta cells produce insulin

• Delta cells produce peptide hormones identical to GH-IH (somatostatin)

• pancreatic polypeptide cells (PP cells) produce pancreatic polypeptide (PP)

When blood glucose level increases, beta cells secrete insulin, stimulating transport of glucose into target cells

When blood glucose level decreases, alpha cells secrete glucagon, stimulating glycogen breakdown and glucose release by liver.

Insulin

Beta cells

• peptide hormone released by beta cells

Effect on target cells:

• Accelerating glucose uptake, use, and enhancing ATP production

• stimulating glycogen formation

• stimulating amino acid absorption and protein

• stimulating triglyceride formation in adipocytes

Glucagon

Released by alpha cells and mobilizes energy reserves

Effect on target cells:

• stimulating breakdown of glycogen in skeletal muscle fibers and liver cells

• stimulating breakdown of triglycerides in adipocytes

• stimulating production and release of glucose in liver cells (gluconeogenesis)

Somatostatin

Delta cells

• paracrine regulation of insulin and glucagon secretion

Hyperglycemia

abnormally high glucose levels in the blood

diabetes mellitus

High glucose concentrations that overwhelm reabsorption capabilities of kidneys

• glucose appears in urine

• polyuria: urine volume become excessive

Type 1 diabetes

Juvenile. Inadequate insulin production by pancreatic beta cells

• patients require daily injections or continuous infusion of insulin

• Approx. 5% of cases

• usually develops in children and young adults

Type 2 diabetes

Acquired

• most common form

• usually, normal amounts of insulin are produced, at least initially

• tissues do not respond properly (insulin resistance)

• associated with obesity; weight loss can be an effective treatment

Complications of poorly managed diabetes

• kidney degeneration

• retinal damage (diabetic retinopathy): may lead to blindness

• early heart attacks (3 to 5xs more likely)

• peripheral nerve problems (diabetic neuropathies)

• peripheral tissue damage due to reduced blood flow

• tissue death, ulceration, infection, and amputation.

Organs with secondary endocrine functions

• intestines: digestive system

• kidneys: urinary system

• heart: cardiovascular system

• thymus: lymphatic system

• gonads: reproductive system

Heart (secondary endocrine function)

Produces natriuretic peptides (ANP and BNP)

• When blood volume becomes excessive

• Actions opposes those of angiotensin II

• Resulting in reduction in blood volume and BP

Thymus (secondary endocrine function)

Produces thymosin (blend of several hormones)

• promotes development and maturation of lymphocytes

Adipose tissue (secondary endocrine function)

Produces leptin (a peptide hormone)

• Provides feedback control of appetite

• maintains normal levels of GnRH and gonadotropin synthesis