Nature of hormones

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Nature of hormones
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What is a hormone?

• Hormone
• Greek I excite or I arouse
• Classical definition
• Chemical messenger released by one type of cells
  and carried in the bloodstream to act on specific
  target cells
• Modern definition
• Includes factors produced and used locally
  without entering the blood stream

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• Endocrine factors
• Released and carried in the blood
• Classical hormones
• Autocrine factors
• Released and used by the same cells
• Paracrine factors
• Affect function of neighboring cells without
  entering the blood stream
• Interstitial fluid

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GnRH
Hypothalamus
FSH
LH
Estradiol
Pituitary gland
Ovary
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Granulosa cells
Basement membrane
Antrum
Oocyte
Theca externa
Theca interna
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Granulosa cells (GC)
Theca cells (TC)
Basement membrane
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General characteristics of hormones

• Very low in concentrations
• Ppb (ng/ml) or ppt (pg/ml)
• Very specific receptor
• One hormone, one receptor

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Chemical nature of hormones

• Classes
• Lipids
• Steroids
• Eicosanoids
• Proteins
• Short polypeptides
• Large proteins
• Chemical modification through glycosylation
• Amino acid derivatives

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Steroid hormones

• Derivative of cholesterol
• Large molecule
• Hydrocarbon ring
• Highly hydrophobic
• Source
• Diet
• De Novo synthesis
• Found in cell membrane

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Cholesterol and its derivatives

• Derivatives
• Vitamin D
• Bile acid
• Lipid digestion
• Steroid hormones
• Sex steroids
• Adrenal steroild
• All cholesterol derivatives contain sterol ring

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Steroid hormones

• Origins
• Adrenal
• Mineralocorticoids
• Affect mineral homeostasis
• Glucocorticoids
• Affect glucose metabolism and immune function
• Gonads (testis and ovaries)
• Estrogens
• Progestins/progestagens
• Androgens

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Eicosanoids

• Metabolites of 12-C fatty acid
• Arachidonic acid
• Prostaglandins
• Produced by numerous tissues and organs
• Originally isolated from prostate gland secretion
• Inflammatory reaction
• Reproduction
• Thromboxanes, leukotriens, and prostacyclins

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Protein hormones

• Short chain of amino acids
• Neurohormones
• GnRH (10)
• Oxytocin (9)
• TRH (3)

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Protein hormones

• Large polypeptides
• Linear chain
• Subunits
• Linked by disulfide bridge(s)
• 3-D structure
• Critical for interaction with receptor

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• Chemical modification
• Glycosylation
• Common in gonadotropins (LH, FSH, hCG, eCG)
• Sulfation
• Acetylation

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Protein hormones

• Isoform and variants
• Amino acid substitution
• Gene duplication

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Amino acid metabolites

• Tyrosine metabolites
• Thyroid hormones
• Thyroxine
• Triiodothyronine
• Adrenal medulla
• Epinephrine
• Norepinephrine
• Dopamine
• Often used as neurotransmitters

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Endocrine glands

• Composition
• Parenchyma (mass of cells)
• Secretory cells
• Blood vessels
• Highly vasucualized
• No ducts
• Permanent or transient
• Pituitary, adrenal, pancreas etc
• Ovarian follicle and corpus luteum

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Cells that produce hormone

• Specialized secretory cells
• Usually one type of cells produce one hormone
• Neurons
• Hypothalamus
• Posterior pituitary
• Adrenal medulla

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Hormone synthesis

• Protein hormones
• Transcription
• Translation
• Physical/chemical modification
• Cleaving of long amino acid chain
  (preprohormones) to generate small peptide
  hormones (GnRH, oxytocin, TRH)
• Interaction and linking of subunits
• 3-D structure

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• Metabolism
• Cholesterol (steroids)
• Smooth ER
• Mitochondria
• Tyrosine
• Thyroid follicular cells (thyroid hormones)
• Thyroglobulin
• Adrenal medulla
• Nerve terminals

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Control of synthesis and secretion

• Neural inputs
• Brain
• Hypothalamus
• Hormonal stimulation/inhibition
• Releasing factors/hormones
• Inhibitory factors
• Feedback system
• Metabolic status
• Stress
• Blood concentrations of substances
• Ca
• Glucose
• Water

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Hormones in circulation

• Peptides and some protein hormones (i.e. insulin)
• Very short half-life
• Degraded by proteolytic enzymes
• Large protein hormones
• Longer half-life

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• Steroids
• Water-insoluble
• Bound to binding globulins (SHBG or CBG) and
  albumin
• Some steroids exist as free form
• Short half-life
• Thyroid hormones
• Thyroxine-binding globulin (TBG)
• Transthyretin