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Chemical Regulating Systems
Hormones: cell to cell communication molecules Made in gland(s) or cells Transported by blood Distant target tissue receptors Activates physiological response Pheromones: organism to organism communication
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Mechanisms of cell-to-cell signaling via hormones
In endocrine function the signal is carried to a distant target via the bloodstream. In neurocrine function the hormone signal originates in a neuron, and after axonal transport to the bloodstream it is carried to a distant target cell. In paracrine function the hormone signal is carried to an
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Anatomy Summary: Hormones
Figure 7-2 (1 of 4)
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Anatomy Summary: Hormones
Figure 7-2 (2 of 4)
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Anatomy Summary: Hormones
Figure 7-2 (3 of 4)
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Anatomy Summary: Hormones
Figure 7-2 (4 of 4)
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Hormones: Function Control of Exert effects at very low concentrations
Rates of enzymatic reactions Transport of ions or molecules across cell membranes Gene expression and protein synthesis Exert effects at very low concentrations Bind to target cell receptors Half-life indicates length of activity
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Enzyme-linked immunosorbent assay (ELISA)
Figure Basic principles of the enzyme-linked immunosorbent assay (ELISA) for measuring the concentration of a hormone (H). AB1 and AB2 are antibodies that recognize the hormone at different binding sites, and AB3 is an antibody that recognizes AB2. E is an enzyme linked to AB3 that catalyzes the formation of a colored fluorescent product (P) from a substrate (S). The amount of the product is measured using optical methods and is proportional to the amount of hormone in the well if there are excess antibodies in the well.
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Hormone dose response curve
Figure A, The general shape of a hormone dose-response curve. Sensitivity is most often expressed as the concentration of the hormone that produces a half-maximal response. B, Alterations in the dose-response curve can take the form of a change in maximal responsiveness (left panel), a change in sensitivity (right panel), or both.
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Hormones: Classification
Peptide or protein hormones Steroid hormones Amine hormones
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Peptide Hormone Synthesis, Packaging, and Release
ECF Cytoplasm Plasma Capillary endothelium Messenger RNA on the ribosomes binds amino acids into a peptide chain called a preprohormone. The chain is directed into the ER lumen by a signal sequence of amino acids. mRNA Ribosome Endoplasmic reticulum (ER) Preprohormone 1 Figure 7-3, step 1
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Peptide Hormone Synthesis, Packaging, and Release
ECF Cytoplasm Plasma Capillary endothelium Messenger RNA on the ribosomes binds amino acids into a peptide chain called a preprohormone. The chain is directed into the ER lumen by a signal sequence of amino acids. Enzymes in the ER chop off the signal sequence, creating an inactive prohormone. mRNA Ribosome Prohormone Signal sequence Endoplasmic reticulum (ER) Preprohormone 1 2 Figure 7-3, steps 1–2
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Peptide Hormone Synthesis, Packaging, and Release
Golgi complex ECF Cytoplasm Plasma Capillary endothelium Messenger RNA on the ribosomes binds amino acids into a peptide chain called a preprohormone. The chain is directed into the ER lumen by a signal sequence of amino acids. Enzymes in the ER chop off the signal sequence, creating an inactive prohormone. The prohormone passes from the ER through the Golgi complex. mRNA Ribosome Prohormone Signal sequence Transport vesicle Endoplasmic reticulum (ER) Preprohormone 1 2 3 Figure 7-3, steps 1–3
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Peptide Hormone Synthesis, Packaging, and Release
4 Active hormone Golgi complex Secretory vesicle ECF Cytoplasm Plasma Peptide fragment Capillary endothelium Messenger RNA on the ribosomes binds amino acids into a peptide chain called a preprohormone. The chain is directed into the ER lumen by a signal sequence of amino acids. Enzymes in the ER chop off the signal sequence, creating an inactive prohormone. The prohormone passes from the ER through the Golgi complex. Secretory vesicles containing enzymes and prohormone bud off the Golgi. The enzymes chop the prohormone into one or more active peptides plus additional peptide fragments. mRNA Ribosome Prohormone Signal sequence Transport Endoplasmic reticulum (ER) Preprohormone 1 2 3 Figure 7-3, steps 1–4
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Peptide Hormone Synthesis, Packaging, and Release
4 5 Active hormone Golgi complex Secretory vesicle ECF Cytoplasm Plasma Peptide fragment Release signal Capillary endothelium Messenger RNA on the ribosomes binds amino acids into a peptide chain called a preprohormone. The chain is directed into the ER lumen by a signal sequence of amino acids. The secretory vesicle releases its contents by exocytosis into the extracellular space. Enzymes in the ER chop off the signal sequence, creating an inactive prohormone. The prohormone passes from the ER through the Golgi complex. Secretory vesicles containing enzymes and prohormone bud off the Golgi. The enzymes chop the prohormone into one or more active peptides plus additional peptide fragments. mRNA Ribosome Prohormone Signal sequence Transport Endoplasmic reticulum (ER) Preprohormone 1 2 3 Figure 7-3, steps 1–5 Release signal can be calcium for cAMP
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Peptide Hormone Synthesis, Packaging, and Release
4 5 To target Active hormone Golgi complex Secretory vesicle ECF Cytoplasm Plasma Peptide fragment Release signal Capillary endothelium Messenger RNA on the ribosomes binds amino acids into a peptide chain called a preprohormone. The chain is directed into the ER lumen by a signal sequence of amino acids. The secretory vesicle releases its contents by exocytosis into the extracellular space. The hormone moves into the circulation for transport to its target. Enzymes in the ER chop off the signal sequence, creating an inactive prohormone. The prohormone passes from the ER through the Golgi complex. Secretory vesicles containing enzymes and prohormone bud off the Golgi. The enzymes chop the prohormone into one or more active peptides plus additional peptide fragments. mRNA Ribosome Prohormone Signal sequence Transport Endoplasmic reticulum (ER) Preprohormone 1 2 3 6 Figure 7-3, steps 1–6
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Activation of a G-protein coupled receptor (GPCR)
Figure 74-4 Mechanism of activation of a G protein-coupled receptor. When the hormone activates the receptor, the inactive α, β, and γ G protein complex associates with the receptor and is activated, with an exchange of guanosine triphosphate (GTP) for guanosine diphosphate (GDP). This causes the α subunit (to which the GTP is bound) to dissociate from the β and γ subunits of the G protein and to interact with membrane-bound target proteins (enzymes) that initiate intracellular signals.
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Peptide Hormone-Receptor Complex
Membrane receptors and signal transduction for peptide hormones Figure 7-5
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Steroid Hormones: Features
Cholesterol-derived Lipophilic and can enter target cell Cytoplasmic or nuclear receptors (mostly) Activate DNA for protein synthesis Slower acting, longer half-life Examples Cortisol, estrogen, and testosterone
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Steroid Hormones: Structure
Steroid hormones are derived from cholesterol Figure 7-6 Lipophilic--not packaged in secretory vesicles, just ooze out of cell by diffusion
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Steroid Hormones: Action
Most hydrophobic steroids are bound to plasma protein carriers. Only unbound hormones can diffuse into the target cell. Cell membrane Interstitial fluid Nucleus Blood vessel Protein carrier 1 Figure 7-7, step 1 Mass action keeps equilibrium between bound & unbound
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Steroid Hormones: Action
Most hydrophobic steroids are bound to plasma protein carriers. Only unbound hormones can diffuse into the target cell. Steroid hormone receptors are typically in the cytoplasm or nucleus. Cell membrane Interstitial fluid Cytoplasmic receptor Nucleus Nuclear Steroid hormone Blood vessel Protein carrier 2 1 Figure 7-7, steps 1–2
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Steroid Hormones: Action
Most hydrophobic steroids are bound to plasma protein carriers. Only unbound hormones can diffuse into the target cell. Some steroid hormones also bind to mem- brane receptors that use second messenger systems to create rapid cellular responses. Steroid hormone receptors are typically in the cytoplasm or nucleus. Cell membrane Interstitial fluid Cytoplasmic receptor Nucleus Nuclear Rapid responses Steroid hormone Blood vessel Protein carrier Cell surface receptor 2 1 2a Figure 7-7, steps 1–2a
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Steroid Hormones: Action
Most hydrophobic steroids are bound to plasma protein carriers. Only unbound hormones can diffuse into the target cell. Some steroid hormones also bind to mem- brane receptors that use second messenger systems to create rapid cellular responses. Steroid hormone receptors are typically in the cytoplasm or nucleus. The receptor- hormone complex binds to DNA and activates or represses one or more genes. Cell membrane Interstitial fluid Cytoplasmic receptor Nucleus Nuclear DNA Rapid responses Steroid hormone Blood vessel Protein carrier Cell surface receptor 2 3 1 2a Figure 7-7, steps 1–3
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Steroid Hormones: Action
Most hydrophobic steroids are bound to plasma protein carriers. Only unbound hormones can diffuse into the target cell. Some steroid hormones also bind to mem- brane receptors that use second messenger systems to create rapid cellular responses. Steroid hormone receptors are typically in the cytoplasm or nucleus. The receptor- hormone complex binds to DNA and activates or represses one or more genes. Activated genes create new mRNA that moves into the cytoplasm. Cell membrane Interstitial fluid Cytoplasmic receptor Nucleus Nuclear DNA Rapid responses Transcription produces mRNA Steroid hormone Blood vessel Protein carrier Cell surface receptor 2 3 1 4 2a Figure 7-7, steps 1–4
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Steroid Hormones: Action
Most hydrophobic steroids are bound to plasma protein carriers. Only unbound hormones can diffuse into the target cell. Translation produces new proteins for cell processes. Some steroid hormones also bind to mem- brane receptors that use second messenger systems to create rapid cellular responses. Steroid hormone receptors are typically in the cytoplasm or nucleus. The receptor- hormone complex binds to DNA and activates or represses one or more genes. Activated genes create new mRNA that moves into the cytoplasm. Cell membrane Interstitial fluid Cytoplasmic receptor Endoplasmic reticulum Nucleus Nuclear DNA Translation Rapid responses Transcription produces mRNA Steroid hormone Blood vessel Protein carrier New proteins Cell surface receptor 2 3 1 4 5 2a Figure 7-7, steps 1–5
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Amine Hormones: Examples
Thyroid hormones Catecholamines Epinephrine Norepinephrine Dopamine
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Amine Hormones: Structure
Tyrosine-derived amine hormones Figure 7-8
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Endocrine Reflex Pathways
Hormones may have multiple stimuli for their release Figure 7-9
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Simple Endocrine Reflex: Parathyroid Hormone
Figure 7-10
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Neurohormones: Major Groups
Adrenal medulla Catecholamines Hypothalamus Anterior pituitary Posterior pituitary
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The Pituitary Gland Anatomy
Figure 7-11
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The Pituitary Gland: Two Fused
Posterior pituitary Vasopressin Oxytocin Figure 7-12 (1 of 4)
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Hypothalamic-Hypophyseal Portal System
Directs Trophic hormone delivery Portal system is a region of the circulation consisting of two sets of capillaries directly connected by a set of blood vessels
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The Pituitary Gland: Two Fused
Hormones of the hypothalamic-anterior pituitary pathway Figure 7-13
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Endocrine Control Three levels Hypothalamic stimulation—from CNS
Pituitary stimulation—from hypothalamic trophic hormones Endocrine gland stimulation—from pituitary trophic hormones
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Negative Feedback Controls
Long-loop feedback Short-loop feedback Figure 7-14
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Control Pathway for Cortisol Secretion
Figure 7-15
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The Hypothalamic-Hypophyseal Portal System
Figure 7-16
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Example of Synergism Figure 7-18
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Endocrine Pathologies
Exogenous medication Replaces and exceeds normal Cause atrophy of gland Figure 7-19 Atrophy--loss of cell mass, cells producing ACTH and Cortisol shrink Ie Cortisone--reduces inflammation (poison ivy, severe allergy, asthma) Treatment must be short Cortisol is a glucocorticoid stimulates gluconeogenisis--formation of carbs from proteins) Excess causes strange form of obesity (Moon Face)
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Excess cortisol
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Endocrine Pathologies
Hypersecretion: excess hormone Tumors or cancer Grave’s disease—thyroxin Hyposecretion: deficient hormone Goiter—thyroxin Diabetes—insulin
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Pathologies: Due to Receptors
Downregulation Hyperinsulinemia Transduction abnormalities Testicular feminization syndrome Pseudohypothyroidism Abnormalities of control mechanisms
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