Transcript Nature of horomes

Nature of hormones
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
• 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
GnRH
Hypothalamus
LH
FSH
Estradiol
Pituitary
gland
Ovary
Granulosa cells
Basement
membrane
Antrum
Oocyte
Theca interna
Theca externa
Granulosa
cells (GC)
Basement membrane
Theca
cells (TC)
General characteristics of
hormones
• Very low in concentrations
– Ppb (ng/ml) or ppt (pg/ml)
• Very specific receptor
– One hormone, one receptor
Chemical nature of hormones
• Classes
– Lipids
• Steroids
• Eicosanoids
– Proteins
• Short polypeptides
• Large proteins
– Chemical modification through glycosylation
– Amino acid derivatives
Steroid hormones
• Derivative of
cholesterol
– Large molecule
• Hydrocarbon ring
– Highly hydrophobic
– Source
• Diet
• De Novo synthesis
– Found in cell
membrane
Cholesterol and its derivatives
• Derivatives
– Vitamin D
– Bile acid
• Lipid digestion
– Steroid hormones
• Sex steroids
• Adrenal steroild
– All cholesterol
derivatives contain
sterol ring
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
Protein hormones
• Short chain of amino acids
– Neurohormones
• GnRH (10)
• Oxytocin (9)
• TRH (3)
Protein hormones
• Large polypeptides
– Linear chain
– Subunits
• Linked by disulfide bridge(s)
– 3-D structure
• Critical for interaction with receptor
• Chemical modification
– Glycosylation
• Common in gonadotropins (LH, FSH, hCG, eCG)
– Sulfation
– Acetylation
Protein hormones
• Isoform and variants
– Amino acid substitution
– Gene duplication
Amino acid metabolites
• Tyrosine metabolites
– Thyroid hormones
• Thyroxine
• Triiodothyronine
– Adrenal medulla
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Epinephrine
Norepinephrine
Dopamine
Often used as neurotransmitters
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
Cells that produce hormone
• Specialized secretory cells
– Usually one type of cells produce one
hormone
• Neurons
– Hypothalamus
– Posterior pituitary
– Adrenal medulla
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
• Metabolism
– Cholesterol (steroids)
• Smooth ER
• Mitochondria
– Tyrosine
• Thyroid follicular cells (thyroid hormones)
– Thyroglobulin
• Adrenal medulla
• Nerve terminals
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
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
• 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