Introduction to Endocrine System

Introduction to Endocrine System

• The endocrine system is a collection of organs with similar properties
• Endocrinology studies hormones, their receptors, intracellular pathways, and related diseases
• Endocrine glands are ductless glands that release hormones directly into the bloodstream
• Hormones are chemical substances that regulate cell and organ activity
• Homeostasis is crucial for life and involves maintaining a stable internal environment
• Regulation of the body's function occurs through both neural and hormonal methods
• Neural regulation is fast-acting and short-lived
• Hormonal regulation is slower but long-lasting

Regulation

• Neural regulation is fast-acting (seconds to minutes), and short-lived
• Hormonal regulation is slow-acting (delayed effect), and long-lasting

Common Endocrine Glands

• Hypothalamus
• Pituitary gland (anterior and posterior)
• Thyroid gland
• Parathyroid gland
• Adrenal gland
• Pancreas (islets of Langerhans)
• Pineal body
• Thymus
• Gonads

General Properties of Hormones

• Hormones do not directly affect the gland that secretes them
• Some hormones affect all body cells, while others affect specific organs
• Hormones trigger biochemical changes that may continue after they leave the bloodstream
• Hormones can have effects beyond their primary function (e.g., insulin stimulating protein synthesis)
• Stimuli that increase the release of some hormones may decrease the release of others with opposing effects (antagonistic hormones)
• Many hormones show cyclic changes in secretion rate (circadian rhythm)
• Hormones may be inactive when secreted and activated in target organs
• Hormones act at very low concentrations
• Unlike enzymes, hormones are constantly lost from circulation due to metabolism

Local Hormones

• Besides general hormones, local hormones act near their release site
• Examples include gastrointestinal hormones (e.g., gastrin, CCK) and neurotransmitters

Forms of Hormones in Blood

• Most hormones circulate in two forms:
  • Free form (active form, small amount)
  • Bound form (inactive form, reservoir for free form, bound to plasma proteins)

General Function of Hormones

• Regulate metabolic processes
• Control growth and metamorphosis
• Essential for homeostasis
• Important for resisting stress
• Crucial for reproduction, particularly through sex hormones

Chemical Nature of Hormones

• Lipid-related:
  • Derived from cholesterol (steroid hormones of adrenal cortex & sex hormones)
  • Lipid-soluble (hydrophobic), easily pass cell membranes
  • Examples include prostaglandins and leukotrienes
• Nitrogen-related:
  • Derived from single amino acids (catecholamines, thyroid hormones)
  • Chain of peptides (3-200 amino acids)
  • Protein hormones (carbohydrate attaches to peptide chain) - hydrophilic
  • Cannot pass cell membranes without carriers

Communication of Hormones

• Endocrine: Hormones released into the bloodstream to affect distant target cells
• Paracrine: Hormones released into the extracellular space to affect nearby target cells
• Neuroendocrine: Hormones released directly into the bloodstream by specialized nerve cells. (e.g., norepinephrine and oxytocin, vasopressin)

Hormone Synthesis

• Requires raw materials (e.g., tyrosine, iodine for thyroid hormone, cholesterol for steroid hormones) and energy (ATP)
• Peptide hormones synthesized in ribosomes, processed through rough ER and Golgi apparatus to be packaged and secreted
• Steroid hormones synthesized in smooth ER and processed by enzymes within mitochondria and cytoplasm

Hormone Storage and Release

• Stored inside cells (pituitary gland, pancreas) or within gland follicles (thyroid gland)
• Stored in granules, released when granules fuse with cell membrane
• Release is stimulated by hormones, substances, and neural signals

Hormone Transport

• Transported via carrier proteins (mostly plasma globulins)
• Carrier proteins protect hormones from degradation & help transport across capillary membranes
• Hormone half-life is the time needed for half of the hormone molecules to be inactivated or removed from circulation (vary by hormone type)

Hormone Utilization (Hormone Receptors)

• Hormones bind to specific protein receptors on target cells to initiate action
• Intracellular receptors: Steroid hormones pass through membranes and bind to receptors inside the cytoplasm that migrate to nucleus
• Membrane receptors: Peptide hormones bind to membrane receptors, activating second messengers
• Thyroid hormones also affect cell function without entering cells directly

Receptors Number

• Number of receptors is not fixed, in response to hormone concentration
• Hormones can increase or decrease receptor quantities
• Hormone action is dependent on receptor type and quantity
• Receptor-mediated upregulation and downregulation due to high or low levels of specific hormones respectively

Downregulation/Desensitization

• Chronic exposure to high hormone concentrations leads to downregulation
• Reduced receptor numbers lead to decreased hormone action
• Presence of antibodies blocking receptors decrease signalling transmission
• Decrease in receptor synthesis or turnover.

Hormone Action

• Hormones bind to receptors, initiating intracellular effects
• Different actions depend on receptor location

Cell Membrane Receptors

• Hormones bind to receptors on the cell surface which start a signalling cascade.
• G-protein coupled receptors (GPCR) are common for peptide hormones.

Messengers

• Hormones are the first messengers, causing a response in target cells.
• Second messengers, such as cyclic AMP (cAMP), Inositol Triphosphate (IP3) and Diacylglycerol (DAG), lead to enzymatic cascades and cellular responses

Inactivation and Excretion

• Hormones are inactivated after their action or response
• Peptide hormones are inactivated by enzymes (peptidases), primarily in the liver and kidneys.
• Thyroid hormones are deiodinized
• Steroid hormones metabolized in the liver, conjugated to be water-soluble, excreted in urine or bile

Pathway of IP3 and DAG

• Phospholipase C is activated by hormones; cleaving PIP2 into IP3 and DAG.
• IP3 release Ca++ into cytoplasm; triggering effects
• DAG activates protein kinase C

Mechanisms of Feedback Control

• Long-loop: Peripheral target tissue hormones act on the hypothalamus and pituitary
• Short-loop: Hormones from the pituitary inhibit their own release from the hypothalamus

Control of Posterior Pituitary Hormones

• Neurohypophysial hormones are regulated by reflex pathways, not hormonal feedback
• Reflexes triggered by sensory input (e.g., suckling leads to oxytocin release)
• Blood volume/electrolyte changes lead to vasopressin release

Hypothalamus

• Part of the diencephalon, lies below thalamus, forms part of the third ventricle walls.
• Surrounded by optic chiasma, mammillary bodies, and thalamus
• Involved in regulating various physiological functions and endocrine control

Hypothalamic Nuclei

• Supraoptic and paraventricular nuclei control posterior pituitary secretions
• Paraventricular & Supraoptic nuclei synthesize oxytocin & vasopressin and control their secretion from the posterior pituitary.

Anatomical Considerations (hypothalamic-hypophysial portal system)

• Vascular connection between median eminence and pituitary

Magnocellular System

• Supraoptic and paraventricular neurons synthesize and secrete oxytocin and vasopressin

Hypothalamic Hormones

• Hypophysiotropic hormones regulate anterior pituitary function

Feedback Mechanisms

• Peripheral hormones, via hormone concentrations, affect hypothalamic and pituitary release mechanisms

Control of Hypothalamic Hormones

• Various factors (neurotransmitters, organic substances) regulate hypothalamic hormone release
• Stress, neurotransmitters, etc. are examples of stimulating factors, and negative feedback from hormones themselves are examples of inhibitory factors.

Pathophysiological Correlates of Hormone Action

• Hormone depletion/excess can cause an increase/decrease in specific receptor numbers, modifying target cell response
• Example is hyperthyroidism leading to enhanced sympathetic nervous system activity due to the modification of receptors

Some Hormones Receptors Issues

• Autoimmune diseases can create antibodies that interfere with cell function