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

LH FSH

Estradiol

Hypothalamus

Pituitarygland

GnRH

Ovary

Antrum

Granulosa cells

Theca internaTheca externa

Basementmembrane

Oocyte

Granulosa cells (GC) Theca

cells (TC)

Basement membrane

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• 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