56. Basic etiology and pathogenesis of endocrine disorders.

BASIC ETIOLOGY AND PATHOGENESIS OF ENDOCRINE DISORDERS

Endocrine system

• ⭐ Endocrine system - chemical messenger system consisting of glands that release hormones that regulate and integrate body functions

Hormones

• ⭐ Hormones - chemical messengers secreted by endocrine organs and transported throughout the body where they exert their action on specific cells called target cells
• A characteristic of hormones is that a single hormone can exert various effects in different tissues (e.g. estradiol) or, conversely, a single function can be regulated by several hormones (e.g. lipolysis)
• The secretion/release of hormones is stimulated by:

1. Another hormone or itself
2. Levels of ions/nutrients/measures

Structural classification

1. Amines and amino acids

• Catecholamines (norepinephrine and epinephrine)
• Thyroid hormones
• Serotonin
• Melatonin

2. Peptides, polypeptides, glycoproteins, and proteins

• Hydrophilic → bind to superficial membrane receptors
• Thyrotropin releasing hormone (TRH)
• Growth hormone (GH)
• Follicle-stimulating hormone (FSH)

3. Steroids

• Lipophilic → bind to intracellular receptors
• Mineralocorticoids
• Glucocorticoids
• Sex hormones

Hormone function

• Response to stress and injury
• Behavioural reactions
• Growth and development
• Reproduction
• Homeostasis
• Energy metabolism

Synthesis and transport

• Protein and peptide hormones
• Synthesised in the rough endoplasmic reticulum (RER)
• Usually, synthesis involves production of precursor hormone, which is modified by the addition of peptides or sugar units = “prohormone”
• After synthesis and sequestration in the ER, the hormones move into the Golgi complex, where they are packaged in granules or vesicles in the cytoplasm
• Prohormones are converted into hormones in the Golgi complex
• Steroid hormones
• Synthesised in the smooth endoplasmic reticulum (SER)
• Steroid-secreting cells have large amounts of SER
• Certain steroids serve as precursors for the production of other hormones
• Transport
• In the bloodstream, hormones are either free/unbound, or attached to transport carriers
• Peptide and protein hormones are usually free/unbound
• Steroid and thyroid hormones are carried by specific carrier proteins
• Free hormones have a shorter half-life than carrier bound hormones

Paracrine and autocrine actions

• Some hormones and hormone-like substances never enter the bloodstream but instead act locally in the vicinity in which they are released
• Involves functional hypopituitarism and is seen in some emotionally deprived children
• These children usually present with poor growth, pot belly, and poor eating and drinking habits

GH deficiency (dwarfism) in children

• Children with pituitary tumours or agenesis of the pituitary lack somatotrophs
• Laron-type dwarfism - GH levels are normal or elevated, but there is a hereditary defect in IGF production that can be treated directly with IGF-1 replacement anabolic processes in liver