Endocrinology- The study of the biological effects of hormones released by endocrine glands and the diseases caused by their dysfunction.- Endocrine glands – ductless glands the release chemical regulators called HORMONES directly into the extracellular fluid (interstitial fluid and blood).Hormones initially get into interstitial fluid by passing through capillary walls before reaching the blood stream where they are transported throughout the bodyNeurotransmitters vs hormones differ in how they’re released- Neurotransmitters- part of nervous system- released into confined area in a synaptic cleft- Hormones- endocrine system- released directly into blood chemical mediatorsLecture 2Release of Hormones• Hormones are released in response to homeostatic imbalances referred to as STIMULI.• Hormones work via NEGATIVE FEEDBACK to maintain homeostasis• Negative Feedback Mechanism – the biological effects of hormones negate/eliminate the stimuli that caused the release of the hormones3 Stimuli for Hormone release• Humoral stimuli – changes in the levels of chemicals in the body’s humors (bodily fluids) stimulate endocrine glands to release hormones.• Neural stimuli – activation of the nervous system stimulates endocrine glands to release hormones• Hormonal stimuli - released hormones stimulate endocrine glands to release other hormones3 Chemical Structures of Hormones• Biogenic amine hormones – hormones derived from the amino acid TYROSINE; such as dopamine, catecholamines Biogenic hormones are generally polar chemicals• Peptide/protein/glycoproteins hormones– hormones composed of a sequence of amino acids: attain structural complexity; protein with carbohydrate moiety attached; such as oxytocin, insulin, follicle stimulating hormone These hormones are polar chemicals• Steroid hormones – hormones derived from cholesterol; such as testosterone Steroid hormones are non polar chemicalsHormone Interactions- how hormones interact w their target cells• Classical Endocrine Interaction – endocrine gland releases a hormone into the bloodstream which transports the hormone to its target cells. • Paracrine Interaction – endocrine cells release hormone into interstitial fluid surrounding the neighboring target cells. Typically, the endocrine cells and the target cells are “neighbors” – located in the same gland/organ.• Juxtacrine Interaction – endocrine cells are juxtaposed to the target cells in the same organ hence, as the endocrine cells release hormone, the hormone interact directly with its target cells.• Autocrine Interaction – the endocrine cells releasing the hormone acts as target cells for the hormoneLecture 3 (9/9)Hormonal Interrelationships- How hormones affect the biological actions of other hormones- Agonism – a hormone binds to the receptors of another hormone and mimics the biological effects of that hormone- Antagonism – a hormone binds to the receptors of another hormone blocking the hormone from binding to its own receptors; No biological effectsof that hormone observed- Permissiveness – the biological effects of a hormone (bound to its own receptors), increases the levels of another hormone and/or increases the number of receptors of that hormone resulting in the overall increase in the biological effects of that hormone- Cooperativityo hormone B binds to hormone A receptors to elicit biological effects onhormone Ao Hormone B binds to hormone B recetor to elicit the effects of hormone Ao Results in a conducive biological effect in the same target tissueo First hormone to act has a permissive effect on the 2nd hormone (typically a receptor)o In coopertivity, the first hormone to act has a permissive effect on the second hormone- Synergism- o a group of hormones released at the same time bind to their individual (cognate, specific) receptors on/in the same target tissue tohave the same biological effecto Overall biological effect is greater than the sum of the individual hormonal effect Ex/ lactation- amount of milk being produced is greater than the individualStructure of Cell Surface Receptors- Transmembrane proteins embedded in the cell membrane of the target cells exposed to the exterior and interior of the target cells- Each cell surface receptor has 3 parts Ectodomain, transmembrane domain, cytoplasmic domain:o Ectodomain- exposed on the surface of the target cell that binds the hormone in the extracellular fluido Transmembrane domain- hydrophobic region (hydrophobic amino acids) of the hormone receptor that traverses the lipid bilayer of the cell membraneo Cytoplasmic domain- located in the cytoplasm of the target cells and linked to a regulatory protein--- either G-protein or Tyrosine kinaseIntracellular Receptors ****Structure: consists of 3 parts:1. Steroid-binding domain:- Steroid hormone and Thyroid hormone binding sites- Associated with heat shock proteins which mask the DNA-binding domain of a resting receptor2. DNA-binding domain:- Contains 2 loops of zinc fingers- Zinc fingers associate with the Hormone-Responsive Elements(HREs) in the target genes . - HREs are palindromic sequences in the target genes unique to each hormone3. Transactivation domain:- Involved in activating transcription of the target genesCytoplasmic Receptors1. Non polar steroid hormone diffuses through the plasma membrane of the target cells and binds to the ligand-binding domain of the cytoplasmic receptor2. The steroid hormone-receptor complex undergoes a conformational change that results in the dissociation of the heat-shock proteins.3. The steroid hormone-receptor complex undergoes compaction and translocates into the nucleus4. The steroid hormone-receptor complexes dimerize and binds with 4 zinc fingers to the HRE (Hormone Responsive Element) on the target genes to regulate transcription –transcription may be stimulated or inhibited5. Stimulatedthe proteins synthesized mediate reactions which are attributed to the biological actions of the steroid hormoneInhibited the absence of these proteins in the target cell results in the inhibition of certain reactions which are attributed to the biological actions of the steroid hormoneNuclear Receptors1. Steroid hormone or thyroid hormone diffuses through the plasma membraneand then through the nuclear membrane to bind to the ligand-binding domain of its receptors2. Hormone-receptor complex undergoes a conformational change and heat-shock proteins dissociate3. With