The Endocrine System Overview

The Endocrine System

• Homeostasis is a state of chemical and thermal balance, maintaining a stable internal environment.
• Nervous and endocrine systems maintain homeostasis.
• Endocrine system is responsible for long-term processes like growth, development, and reproduction.
• Nervous system manages rapid communication and split-second responses.
• The neuroendocrine response is a combined action of both systems maintaining homeostasis.
• Endocrine system communicates through hormones released directly into the bloodstream and ECF (extracellular fluid).
• Target cells have specific receptors to bind and interpret hormones.
• Hormones change the type, amount, and activity of enzymes and proteins, influencing responses to internal and external changes in the environment.

Classes of Hormones

• Amino acid derivatives are derived from tyrosine and tryptophan, including thyroid hormone and catecholamines (epinephrine, norepinephrine, and dopamine). Melatonin is a primary tryptophan derivative.
• Peptide hormones are chains of amino acids, often activated before or after secretion. Glycoproteins have carbohydrate chains, while other small polypeptides and proteins are shorter chains.
• Lipid derivatives include eicosanoids (leukotrienes, prostaglandins, thromboxanes, and prostacyclins) as well as steroid hormones (structurally similar to cholesterol). Steroids are typically bound to transport proteins in the blood.

Mechanisms of Hormone Action

• Hormones interact with specific receptors on target cells.
• The number and type of receptors determine a cell's sensitivity to a hormone.
• Lipid-soluble hormones (steroids and eicosanoids) cross the plasma membrane to bind intracellular receptors, affecting gene expression directly.
• Water-soluble hormones (catecholamines and peptides) bind to receptors on the cell surface, activating second messenger systems.
• Second messenger systems, like cyclic AMP or calcium ions, amplify the signal and create effects within the cell.

Indirect Effects of Hormones

• Hormone-receptor binding on the cell surface activates a G protein, which can activate other enzymes like adenylate cyclase.
• Adenylate cyclase converts ATP to cyclic AMP (cAMP), a second messenger.
• cAMP activates protein kinases that phosphorylate other proteins, leading to cellular responses.
• Hormone binding to a different receptor type activates the enzyme phospholipase C (PLC), ultimately increasing calcium levels in the cell.
• Calcium acts as another second messenger, activating enzymes and altering cellular functions.

Direct Effects of Hormones (Steroids)

• Steroid hormones diffuse through the cell membrane.
• Hormones bind to receptors in the cytoplasm or nucleus of the target cell.
• Hormone-receptor complexes bind to DNA, activating or deactivating specific genes, changing transcription and protein synthesis.
• This affects the target cell's metabolic activity and structure.

Direct Effects of Hormones (TH) - Thyroid Hormones

• Thyroid hormones cross the plasma membrane and bind to receptors in the nucleus.
• Hormone-receptor complexes activate certain genes, influencing the rate of transcription.
• Metabolic activity is altered through changes in enzyme concentrations within cells, particularly in mitochondria that increase ATP production.

Modulation of Target Cell Sensitivity

• Cells can adjust sensitivity to hormones by changing receptor numbers.
• Up-regulation increases receptor numbers, making the cell more sensitive to a hormone.
• Down-regulation decreases receptor numbers, making the cell less sensitive to a hormone.
• Factors like high hormone concentrations and/or diseases lead to down-regulation or up-regulation.

Control of Hormones Negative Feedback

• Negative feedback: homeostasis is maintained through the regulation of hormone amounts in response to fluctuations.
• Endocrine glands adjust hormone production in response to changes in their concentrations.
• Declining hormone levels trigger increased hormone production; rising levels trigger inhibition of hormone production.

Negative Feedback Loop Example

• Hypothalamus releases TRH.
• Anterior pituitary releases TSH.
• Thyroid releases T3 and T4.
• Rising T3 and T4 levels inhibit the release of TRH and TSH.
• Maintaining a stable output of hormones.

Positive Feedback Loop Examples

• Childbirth – uterine contractions. Positive feedback reinforces the stimulus.
• Blood clotting – platelets aggregate to stop bleeding. Positive feedback accelerates the process until homeostasis is reached

The Pituitary Gland

• AKA the master gland, it controls/influences many other glands.
• Three main parts: anterior lobe, posterior lobe, and intermediate.
• Anterior lobe (adenohypophysis) - makes and releases its hormones (tropic hormones).
• Posterior lobe (neurohypophysis) - stores and releases hypothalamic hormones (ADH & OT).
• Intermediate lobe (pars intermedia) - produces melanocyte-stimulating hormone (MSH).

Anterior Pituitary

• Composed of 5 cell types: -Thyrotropes (TSH) – thyroid stimulating hormone
• Corticotropes (ACTH) – adrenal cortex stimulating hormone. -Gonadotropes (FSH & LH) – follicle-stimulating hormone and luteinizing hormone.
• Somatotropes (GH)- growth hormone.
• Mamotropes (PRL) – prolactin

Posterior Pituitary

• Stores and releases Antidiuretic hormone (ADH) and Oxytocin (OT).
• No hormones are synthesised in the posterior lobe.

Hormones of the Adrenal Glands

• Adrenal cortex (3 zones): zona glomerulosa, zona fasciculata, zona reticularis
• Mineralocorticoids (zona glomerulosa) – regulation of mineral balance, especially sodium (aldosterone).
• Glucocorticoids (zona fasciculata) – carbohydrate and protein metabolism, stress response (cortisol).
• Gonadocorticoids (zona reticularis) – small amounts; conversion to sex hormones

Adrenal Medulla

• Produces epinephrine and norepinephrine (fight-or-flight response).
• Sympathetic Nervous System stimulation leads to increased release of these hormones.
• Increased blood glucose, fatty acid mobilization, increased cardiac rate, and elevated blood pressure.

Pancreas

• Both exocrine and endocrine functions
• Exocrine function: 99% of acini—produce alkaline pancreatic juice with digestive enzymes
• Endocrine function: islets of Langerhans (~2 million cells).
• Alpha cells: produce glucagon
• Beta cells: produce insulin
• Delta cells: produce somatostatin
• F Cells: produce pancreatic polypeptide

Diabetes

• Type 1 diabetes: characterized by inadequate insulin production by pancreatic beta cells.
• Type 2 diabetes: tissues don't respond properly to insulin.
• Both types lead to elevated blood glucose levels.

Secondary Endocrine Functions

• Intestines: hormones for digestive control.
• Kidneys: erythropoietin (EPO), calcitriol, renin.
• Heart: atrial natriuretic peptides (ANP) and brain natriuretic peptide (BNP).
• Thymus: thymosins (T lymphocyte development).
• Gonads: hormones for reproduction.

Hormonal Interactions

• Antagonistic hormones: have opposing effects (e.g., calcitonin and parathyroid hormone).
• Synergistic hormones: have additive effects (e.g., glucose sparing of GH and glucocorticoids).
• Permissive hormones: 1 hormone is needed for another to exert its effect (e.g., TH is needed for full effects of epinephrine).
• Integrative hormones: different hormones in different tissues work together in combination (e.g., calcitriol and PTH).

General Adaptation Syndrome (GAS)

• Three phases of stress response: alarm, resistance, exhaustion.
• Alarm phase: immediate response involving epinephrine and norepinephrine.
• Resistance phase: longer-term response with increased glucocorticoid levels.
• Exhaustion phase: body reserves are depleted, and homeostasis cannot be maintained.

Additional Topics

• Pineal gland: produces melatonin involved in circadian rhythms and regulates reproductive function also related to the color of the skin.
• Kidney Function: Kidney produces renin to help regulate water and electrolyte balance.
• Hypothalamic-Pituitary Axis: Hypothalamus regulates the anterior pituitary gland.
• Hypophyseal Portal System: Specialized blood vessels connecting the hypothalamus and anterior pituitary to allow hormones rapid movement with limited dilution.