Endocrinology

• 2nd major control system in the body• “study of chemical messengers (hormones)

secreted by endocrine glands and other tissues”

• major role: to maintain homeostasis• coordinates many processes:

– metabolism, respiration, excretion, reproduction

Homeostasis

• concept of Claude Bernard• individuals live with 2 environments:

– external milieu– internal milieu

• bodies control internal milieu > allows independence from external milieu

Homeostasis

• contents of “fluid environment”:– glucose– amino, fatty acids– Electrolytes

• result: wide distribution of mammals to all types of habitats

Feedback systems

• endocrine and other sensory cells have “setpoint” for monitoring substances in blood

• low levels > hormone released (e.g. Ca2+ and parathyroid hormone)

• some systems shut off due to negative feedback• some are regulated by positive feedback

Other mechanisms of regulation

• Actions of opposing hormones– PTH and calcitonin– glucagon and insulin

• the brain / pituitary connection– time of day– temperature– nutrition

Types of cellular communication

Subcategories of hormones

• Neurohormones: produced by nerve cells– Neuropeptides– Nonpeptidergic

neurohormones– Neuromodulators

• Pheromones:– Released to exterior of animal– Modulates response of another animal

• Lumones: released into lumen of GI tract• Chalones: inhibit mitosis• Growth factors: mitogenic peptides

Subcategories of hormones, cont’d.

Protein and peptide hormones

• Made of amino acids• Variable in size (e.g., TRH=3 amino acids)• Ring structures may be present (e.g., oxytocin,

vasopressin)• Many synthesized in precursor form > modified

prior to secretion (e.g., insulin; Fig. 1.8)• Some consist of two peptide chains (e.g., pituitary

glycoproteins)• Possible glycosylation• Transmembrane receptors

Hormones derived from tyrosine

• Enzymes present in cells determine which catecholamine will be synthesized

• Tyrosine > DOPA > dopamine > norepinephrine > epinephrine (handout)

• Catecholamines can be hormones, neurotransmitters

• Transmembrane receptors• Thyroid hormones (thyroxine, triiodothyronine)

also derived from tyrosine– T3 > 2 tyrosines with 3 iodine atoms (Fig. 5.3)– T4 > 2 tyrosines with 4 iodine atoms

• Nuclear receptors

Steroid hormones

• Derived from cholesterol• Glucocorticoids (e.g., cortisol), mineralocorticoids

(aldosterone)• Gonadal steroids (progesterones, androgens,

estrogens)• “generational” relationships• Enzymes present in cell determine steroids

produced• nuclear receptors• bind to proteins in blood > extends half-life• in liver, conjugated to glucuronic acid or sulfated

> inactivated

Terms to include:

• DNA, gene, codon, structural gene (“coding sequence”), regulatory regions, introns, exons

• Transcription, RNA polymerase, RNA, mRNA

• Translation, ribosomes, tRNA, amino acids, amino terminus, carboxy terminus

Peptide synthesis

• nucleotide sequence of gene dictates amino acid sequence of peptide

• sequence is transcribed into RNA• introns splicing occurs• mRNA leaves nucleus• translation occurs on ribosomes• peptides transported to RER and then Golgi

for modification(s) and packaging

Prohormones

• “precursors” to peptide hormones• often, peptides are spliced from much larger

hormones• examples:

– oxytocin– gonadotropin-releasing hormone (GnRH)

• precursors are packaged with endopeptidases in secretory vesicles

Peptide circulation and metabolism

• half-life = time required for half of molecules to be cleared / inactivated

• short a.a. sequence > short half life• inactivated by peptidases• drug design• peptides activate membrane-bound

receptors on target cells