Comprehensive Hormone Notes

Overview of Hormones

• Hormones are the body's chemical messengers that are produced in one region and affect a different region of the body via the bloodstream and tissues.
• They act slowly over time and influence many processes: growth and development, metabolism, how energy is obtained from foods, sexual function, reproduction, and mood.
• A hormone will only act on a target tissue if the receptor fits like a key fits a lock; specificity of receptors dictates which tissues respond.
• Hormones can be thought of as keys and receptors as locks on cells; if the key fits the lock, the receptor will trigger a response.
• The course will cover chemical classification of hormones, mechanisms of action and receptors, and feedback mechanisms controlling secretion.

Structural Classification of Hormones

• Most commonly hormones are categorized into four structural groups, with a broader family sometimes described including fatty acid derivatives (eicosanoids):
  • Peptides and proteins
  • Steroids
  • Amino acid derivatives
  • Fatty acid derivatives (eicosanoids)
• These chemical groups affect distribution, receptor type, and functions of the hormones.

Amino Acid-Derived Hormones

• Derived from amino acids; retain an amino group; polarity varies, often hydrophilic and water-soluble, affecting their ability to cross the plasma membrane easily.
• Tyrosine-derived hormones form two major groups:
  • Thyroid hormones: basically two tyrosine units with iodine substitutions; T3 and T4. T3 (triiodothyronine) has 3 iodine atoms; T4 (thyroxine) has 4 iodine atoms.
  • Catecholamines: epinephrine and norepinephrine; used as both hormones and neurotransmitters.
• Other amino acid derivatives include:
  • Tryptophan derivatives: serotonin and melatonin.
  • Histidine derivative: histamine.
• These amino acid derivatives differ in receptor types and cellular effects; many are hydrophilic and bind to cell-surface receptors (except where noted for specific lipophilic exceptions).

Peptide and Protein Hormones

• Structure: typically composed of 2 to 200 amino acids (often written as 2–200 amino acids).
• Hydrophilic and water-soluble; bind to receptors on the plasma membrane rather than crossing the membrane.
• Synthesis and processing:
  • A gene is transcribed into messenger RNA (mRNA).
  • Translation occurs at ribosomes or the endoplasmic reticulum to form a peptide precursor.
  • The peptide hormone is processed and folded in the Golgi apparatus and secretory vesicles before secretion into the bloodstream.
• Storage and secretion:
  • Peptide hormones are stored in secretory vesicles until release signals trigger secretion.
• Examples: pituitary hormones; insulin.

Steroid Hormones

• Derived from cholesterol; lipophilic (hydrophobic) and can diffuse through the plasma membrane.
• Not typically stored in endocrine cells; synthesized on demand and diffuse out immediately after synthesis.
• Transport in blood: hydrophobic steroids are usually bound to carrier proteins (proteins) for transport, which protects them from degradation.
• Receptors and action:
  • Receptors are located inside the cell (cytoplasm or nucleus) where they can directly influence gene transcription.
  • This intracellular receptor action leads to longer-term genomic effects.
• Major sources and examples:
  • Produced within gonads (sex hormones) and adrenal cortex (e.g., corticosteroids, aldosterone).
  • Adrenal glands also produce hormones involved in osmoregulation and metabolism, such as cortisol.
• Synthesis pathway (typical):
  • Cholesterol → pregnenolone → various steroids (e.g., cortisol, aldosterone, testosterone) → estradiol in women via further modifications.
• Characteristics:
  • Hydrophobic nature means they require carrier proteins in the bloodstream and can cross cell membranes to reach intracellular receptors.

Fatty Acid-Derived Hormones (Eicosanoids)

• Derived from polyunsaturated fatty acids; the principal group of fatty acid-derived hormones.
• Major members: prostaglandins, prostacyclins, leukotrienes, thromboxanes.
• Precursor: arachidonic acid; stored in membrane lipids and released by enzymatic action to form eicosanoids.
• Specific production:
  • The particular eicosanoids produced in a cell depend on the expressed enzymes within that cell.
• Characteristics:
  • Very rapid inactivation; typically active for only a few seconds.
• Note: these are not classical circulating hormones like peptide or steroid hormones, but act as local or paracrine/autocrine mediators.

Transport, Storage, and Binding in Blood

• Hydrophobic (lipophilic) hormones (e.g., steroids) usually travel in the blood bound to carrier proteins.
• Hydrophilic (water-soluble) hormones (e.g., peptide hormones, catecholamines) typically travel freely in the plasma or with less extensive protein binding.
• The localization of receptor type (membrane vs intracellular) is related to whether a hormone is hydrophilic or hydrophobic.

Receptors and Mechanisms of Hormone Action

• Hydrophilic hormones (water-soluble): bind to receptors on the plasma membrane; activate intracellular signaling cascades (second messengers).
  • Primary mechanism often involves G protein-coupled receptors (GPCRs).
  • Example signaling pathway: hormone binds receptor → activates G protein (guanosine diphosphate (GDP) to guanosine triphosphate (GTP) exchange) → activates adenylate cyclase → increases cyclic adenosine monophosphate (cAMP) → activates protein kinase A (PKA) → phosphorylates target proteins → metabolic effects.
  • Analogy: a doorbell triggers a reaction inside without the hormone entering the cell.
  • Second messenger: ext{cAMP} = ext{cyclic adenosine monophosphate}; reaction: ext{ATP}
    ightarrow ext{cAMP} + ext{PP}_i via adenylyl cyclase.
• Lipid-soluble hormones (steroids and thyroid hormones): bind to receptors inside the cell (cytoplasmic or nuclear receptors); the hormone-receptor complex often acts as a transcription factor influencing gene expression.
• Insulin example: a peptide hormone; receptor-mediated actions on target tissues; requires membrane receptor and downstream signaling without entering the nucleus directly.

Target Cells, Receptors, and Sensitivity

• Target cells respond to hormones only if they possess the appropriate receptor.
• The number and availability of receptors determine the cell’s sensitivity to a given hormone.
• Receptors can be shared by multiple hormones or be specialized for a single hormone.
• Receptor regulation:
  • Upregulation: an increase in receptor numbers in response to higher hormone levels, increasing cell sensitivity.
  • Downregulation: a decrease in receptor numbers in response to higher hormone levels, reducing sensitivity.

Hormone Interactions at Target Cells

• Permissiveness: one hormone cannot exert its full effect without another hormone present (e.g., thyroid hormone increases receptor availability for epinephrine).
• Synergism: two hormones produce a greater combined effect than the sum of their individual effects (e.g., maturation of female eggs involves interaction between FSH and estrogen).
• Antagonism: one hormone opposes the action of another on the same target cell (e.g., calcitonin and parathyroid hormone have opposing effects on calcium homeostasis).

Control of Hormone Secretion: Signals Initiating Release

• Three primary signal types initiate hormone production and secretion:
  • Neural (neurostimuli): nerve fibers innervate endocrine glands; example includes hypothalamic input to the posterior pituitary and sympathetic stimulation of the adrenal medulla.
  • Humoral (humoral stimulation): changes in the blood or extracellular fluids trigger hormone release (e.g., glucose levels stimulating insulin release).
  • Hormonal (neurohormonal): hormones from one endocrine gland stimulate another gland to secrete its hormones (e.g., hypothalamic releasing hormones acting on the anterior pituitary).
• Key example of neural/neurohumoral control: the hypothalamus–posterior pituitary axis; hypothalamic neurons send signals to the posterior pituitary to release stored hormones (e.g., oxytocin, vasopressin).
• Sympathetic division example: preganglionic sympathetic neurons stimulate the adrenal medulla to release epinephrine.
• Humoral example: rising glucose stimulates insulin release from the pancreas.

Regulation of Hormonal Secretion: Feedback Mechanisms

• Hormone levels are regulated by feedback mechanisms to maintain homeostasis.
• Negative feedback: the response of the controlled condition reverses or counteracts the initial stimulus; acts like a thermostat.
  • Example: insulin release after a meal lowers blood glucose, which then reduces insulin secretion.
  • Example: calcium homeostasis via parathyroid hormone (PTH): when calcium drops, PTH release increases; when calcium rises, PTH release decreases.
  • Another endocrinology example: growth hormone (GH) axis with IGF-1 feedback (see below).
• Positive feedback: amplifies changes rather than reversing them; relatively rare.
  • Classic example: oxytocin release during labor; oxytocin stimulates contractions, which increase pressure and further oxytocin release, continuing until birth.
  • Once the stimulus ends, the system returns to baseline and the positive feedback loop ceases.

Growth Hormone (GH) Axis and Negative Feedback Loops

• Hypothalamus releases growth hormone-releasing hormone (GHRH) → stimulates the anterior pituitary to release growth hormone (GH).
• GH effects include: increased amino acid uptake, protein synthesis, tissue growth, and stimulation of growth in bone and muscle; also glucose metabolism effects (e.g., lipolysis in adipose tissue, glucose mobilization).
• GH stimulates the liver to produce insulin-like growth factor 1 (IGF-1).
• IGF-1 exerts negative feedback on the hypothalamus and pituitary: high IGF-1 levels promote growth hormone-inhibiting hormone (GHIH, also called somatostatin) release, which inhibits GH release from the anterior pituitary.
• GH effects summarized:
  • Growth effects: increased uptake of amino acids, protein synthesis, cell proliferation, and reduced apoptosis; targets bone, muscle, nervous system, and immune cells.
  • Metabolic effects: glucose-sparing actions and support for growth via IGF-1 release.

Negative Feedback Examples in Endocrinology

• Insulin regulation of blood glucose: after meals, elevated blood glucose triggers insulin release; insulin promotes glucose uptake and utilization, lowering blood glucose; falling glucose reduces insulin release (negative feedback).
• Calcium regulation: parathyroid hormone (PTH) increases blood calcium by releasing calcium from bone and increasing renal calcium reabsorption; if calcium rises too high, PTH secretion decreases (negative feedback).

Positive Feedback Example

• Labor and delivery: oxytocin from the posterior pituitary promotes uterine contractions; contractions increase pressure and stimulate more oxytocin release, intensifying contractions until birth.

Tropic Hormones and Hormone Secretion Control

• Tropic hormones are hormones that stimulate other endocrine glands to secrete their hormones.
• Examples:
  • Hypothalamic releasing hormones stimulate the anterior pituitary to release trophic hormones like TSH (thyroid-stimulating hormone), ACTH (adrenocorticotropic hormone), and gonadotropins (LH and FSH).
  • These in turn stimulate their target glands (thyroid, adrenal cortex, gonads) to secrete their hormones.
• It is important to distinguish between tropic (regulating other glands) and non-tropic hormones (direct effects on target tissues).

Notable Endocrine Hormones and Examples Mentioned

• Insulin: a peptide hormone; key in lowering blood glucose.
• Thyroid hormones: T3 and T4; regulate metabolic rate and many tissues.
• Catecholamines: epinephrine and norepinephrine; act as hormones and neurotransmitters; rapid metabolic effects.
• Steroid hormones: cortisol, aldosterone, testosterone, estrogen; derived from cholesterol; act mainly via intracellular receptors to regulate gene expression.
• Eicosanoids: prostaglandins, prostacyclins, leukotrienes, thromboxanes; local mediators with very short half-lives.

Quick Facts and Key Distinctions

• Hydrophilic (water-soluble) hormones bind plasma membrane receptors and use second messenger systems (like cAMP via G proteins) for rapid effects.
• Hydrophobic (lipid-soluble) hormones bind intracellular receptors and often regulate gene transcription, leading to slower but longer-lasting effects.
• Receptor number and affinity determine target cell sensitivity; changes in receptor density alter responsiveness (upregulation/downregulation).
• Hormone interactions can be permissive, synergistic, or antagonistic, shaping the overall physiological response.
• Negative feedback is the predominant control mechanism for maintaining homeostasis; positive feedback is less common and typically occurs in specialized physiologic processes (e.g., parturition).

Key Formulas and Notation

• Cytosolic second messenger cascade (example for water-soluble hormone):
  • ext{Hormone}
    ightarrow ext{Receptor (plasma membrane)}
    ightarrow G_s
    ightarrow ext{Adenylyl cyclase}
    ightarrow ext{cAMP}
    ightarrow ext{PKA activation}
    ightarrow ext{Phosphorylation of target proteins}
• Activation of adenylyl cyclase converts ATP to cyclic AMP:
  • ext{ATP}
    ightarrow ext{cAMP} + ext{PP}_i
    
• Thyroid hormone iodine content (conceptual): T3 has 3 iodines, T4 has 4 iodines.
• Amino acid-derived hormones include two major tyrosine-based groups: thyroid hormones and catecholamines.

Connections to Foundational Principles and Real-World Relevance

• Hormone signaling illustrates core biology concepts: receptor-ligand specificity, signal transduction, feedback regulation, and homeostasis.
• Understanding peptide vs steroid signaling helps explain why some drugs target membrane receptors (peptide analogs) versus intracellular receptors (steroid-like drugs).
• The principle of feedback loops (negative and positive) underpins many clinical conditions, such as diabetes (insulin signaling, negative feedback on glucose) and calcium disorders (PTH regulation).
• Tropic hormones explain how the hypothalamus-pituitary axis coordinates endocrine function across multiple organs, shaping growth, metabolism, stress responses, and reproduction.

End of notes