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 body Neurotransmitters vs hormones differ in how they re released Neurotransmitters part of nervous system released into confined area in a Hormones endocrine system released directly into blood chemical synaptic cleft mediators Lecture 2 Release of Hormones STIMULI Hormones are released in response to homeostatic imbalances referred to as 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 hormones 3 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 Hormonal stimuli released hormones stimulate endocrine glands to glands to release hormones release other hormones 3 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 chemicals Hormone 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 hormone Lecture 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 effects of 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 Cooperativity hormone A hormone A o hormone B binds to hormone A receptors to elicit biological effects on o Hormone B binds to hormone B recetor to elicit the effects of o Results in a conducive biological effect in the same target tissue o 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 to have the same biological effect o Overall biological effect is greater than the sum of the individual hormonal effect the individual Ex lactation amount of milk being produced is greater than Structure 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 fluid o Transmembrane domain hydrophobic region hydrophobic amino acids of the hormone receptor that traverses the lipid bilayer of the cell membrane o Cytoplasmic domain located in the cytoplasm of the target cells and linked to a regulatory protein either G protein or Tyrosine kinase Intracellular Receptors Structure consists of 3 parts 1 Steroid binding domain Associated with heat shock proteins which mask the DNA binding domain of Steroid hormone and Thyroid hormone binding sites a resting receptor 2 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 hormone 3 Transactivation domain Involved in activating transcription of the target genes Cytoplasmic Receptors 1 Non polar steroid hormone diffuses through the plasma membrane of the target cells and binds to the ligand binding domain of the cytoplasmic receptor 2 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 nucleus 4 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 inhibited 5 Stimulated the proteins synthesized mediate reactions which are attributed to the biological actions of the steroid hormone Inhibited 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 hormone Nuclear Receptors 1 Steroid hormone or thyroid hormone diffuses through the plasma membrane and then through the nuclear membrane to bind to the ligand binding domain of its receptors 2 Hormone receptor complex undergoes a conformational change and heat shock proteins dissociate 3 With the 2 zinc fingers in the DNA binding domain the Hormone receptor complex binds to of the palindromic sequence of the HRE the other of the HRE is ALWAYS occupied by retinoic acid receptor RXR