Hormone Synthesis and Structure

Steroid Hormones

• Steroid hormones are synthesized from cholesterol and are not stored.
• They have a similar structure to cholesterol.
• They are produced from plasma.

Amine Hormones

• Amine hormones are derived from tyrosine.
• Thyroid and adrenal medullary hormones are formed from tyrosine.

Thyroid Hormones

• Thyroid hormones are stored in the thyroid gland.
• They are formed by the actions of enzymes in cytoplasmic compartments of glandular cells.
• Hormones are secreted from thyroglobulin, released into the blood, and combine with plasma proteins to reach target areas.

Adrenal Medulla Hormones

• Adrenal medulla forms epinephrine (four times more) and norepinephrine.
• Catecholamines are stored in vesicles, waiting to be released.
• Proteins hormones are stored in secretory granules.

Hormone Secretion and Clearance

• Hormones are secreted in response to a stimulus.
• The duration of action varies among different hormones.
• Some hormones, like norepinephrine and epinephrine, take effect in seconds to a minute after gland stimulation.
• Hormones like thyroxine and growth hormones take months to achieve full effect.

Hormone Concentrations and Secretion Rates

• Hormone concentrations in the circulating blood are extremely small, measured in micrograms or milligrams.
• Hormone production rates are also very small, with a daily average production rate of micrograms or milligrams.

Hormone Secretion and Classification

• Neurotransmitters are released by axon terminals of neurons into synaptic junctions.
• Endocrine hormones are secreted by glands directly into the circulating blood.
• Neuroendocrine hormones are secreted by neurons into the circulating blood.
• Paracrine secretion involves cells releasing substances into extracellular fluid, affecting neighboring cells of different types.
• Autocrine secretion involves cells releasing substances into extracellular fluid, affecting the function of the cell that produces them.
• Cytokines are secreted by cells into extracellular fluid and can work as autocrine, paracrine, and endocrine hormones.

Hormone Classification

• Three general classes of hormones exist: proteins and polypeptides, steroids, and derivatives of the amino acid tyrosine.
• Proteins and polypeptides are secreted by: • Posterior and anterior pituitary gland • Pancreas (insulin and glucagon) • Parathyroid gland (parathyroid hormone) • Other glands
• Steroids are secreted by: • Adrenal cortex (cortisol and aldosterone) • Ovaries and placenta (estrogen and progesterone)
• Derivatives of the amino acid tyrosine are secreted by: • Thyroid (thyroxine and triiodothyronine)

Hormone Storage

• Polypeptide and protein hormones are stored in secretory vesicles until needed.
• Polypeptides with >100 amino acids are classified as proteins.

Feedback Control of Hormone Secretion

• Negative feedback mechanism prevents overactivity of hormone systems by suppressing further production of hormones to prevent oversecretion.
• Negative feedback can work on target tissues rather than secretion rates.

Role of Negative Feedback in Hormone Regulation

• Prevents over secretion of hormones, such as LH (Lutenizing hormone) during ovulation in females.
• Acts as a counterbalance to positive feedback mechanisms, which can cause surges of hormones.

Cyclical Variations in Hormone Release

• Hormone release follows a cyclical pattern, influenced by circadian clocks (daily rhythms).
• Examples of cyclical variations:
  • Growth hormone production is higher during early stages of sleep and decreases towards the end of sleep.
  • The 28-day ovulation cycle in females, preparing the body for breeding.

Positive Feedback Mechanism

• Can cause surges of hormones, such as LH in ovulation.
• Works in conjunction with negative feedback to regulate hormone release.

Transport of Hormones in the Blood

• Thyroxine and steroid hormones are not freely moving in the blood because they are bound to plasma proteins.
• Binding to plasma proteins is necessary for clearance of hormones from plasma.
• When hormones reach their target tissues from capillaries, they are released from plasma proteins.

Clearance of Hormones from the Blood

• Clearance of hormones is influenced by two factors:
  • Rate of hormone production in the blood
  • Rate of removal of hormone in the blood (metabolic clearance rate)
• Metabolic clearance rate is calculated by dividing the rate of plasma removal in the blood by the plasma concentration of the hormone.
• Units of metabolic clearance rate are typically nanograms per milliliter.

Measuring Metabolic Clearance Rate

• To calculate metabolic clearance rate, a purified solution of hormone is tagged with a radioactive substance and slowly injected into the bloodstream at a steady rate.
• When the plasma concentration of the hormone reaches a steady state, the rate of plasma removal is divided by the plasma concentration of the hormone to calculate the metabolic clearance rate.

Fate of Hormones in the Blood

• Hormones are cleared from the blood through various routes, including:
  • Liver: hormones are excreted into bile
  • Kidney: hormones are excreted into urine
  • Tissue binding: hormones bind to specific tissues
  • Destruction: hormones are broken down in tissues
• Malfunction of these organs can lead to accumulation of hormones, which can have negative consequences.

Hormone Receptors and Their Activation

• Hormone receptors are specific to binding hormones and are found in three locations:
  • Surface cell membrane (proteins, catecholamines, peptide hormones)
  • Cytoplasm (many steroid hormones)
  • Nucleus (thyroid hormones)
• Number and sensitivity of hormone receptors are regulated through:
  • Inactivation or destruction of protein receptors every minute
  • Hormone secretions to high levels

Intracellular Signaling After Hormone Receptor Activation

• Hormones require their receptors to affect target tissues
• Ion channel-linked receptors:
  • Combine with receptors in the postsynaptic membrane, causing a change in receptor structure
  • Open or close channels for specific ions (e.g., sodium, potassium, calcium)
  • Altered ion movement causes subsequent effects on postsynaptic cells
• Most hormones that open or close ion channels do so indirectly through:
  • G protein–linked receptors
  • Enzyme-linked receptors

G-Protein Linked Hormone Receptors

• Hormones activate receptors that indirectly regulate activity of target proteins by coupling with G proteins.
• G proteins are groups of cell membrane proteins called heterotrimeric guanosine triphosphate (GTP)-binding proteins.

Steroid Hormones and Protein Synthesis

• Steroid hormones cause protein synthesis in target cells.
• Proteins produced can function as enzymes, transport proteins, or structural proteins.
• The sequence of events in steroid hormone function:
  • Steroid hormone diffuses across the cell membrane and binds with a specific receptor protein in the cytoplasm.
  • The combined receptor protein-hormone diffuses into or is transported into the nucleus.
  • The combination binds to specific points on DNA strands in chromosomes, activating transcription process of specific genes to form mRNA.
  • mRNA diffuses into the cytoplasm, promoting translation process at ribosomes to form new proteins.

Example of Steroid Hormone Function: Aldosterone

• Aldosterone is a hormone secreted by the adrenal cortex that binds with the mineralocorticoid receptor in renal tubular cells.
• The sequence of events cited above ensues, leading to the production of proteins that promote sodium reabsorption from the tubules and potassium secretion into the tubules.
• The full action of the steroid hormone is characteristically delayed for at least 45 minutes, with effects lasting several hours or even days.