endocrine system.doc

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Chapter 16: The Endocrine System
endocrinology- the study of hormones and the endocrine glands
-the endocrine system influences metabolic activity by means of hormones (chemical
messengers released into the blood to be transported throughout the body)
endocrine glands- ductless glands; release their hormone into the surrounding tissue fluid
and have a rich vascular and lymphatic drainage that receives their hormones
-includes the pituitary gland, thyroid gland, parathyroid gland, adrenal gland, and pineal
-the hypothalamus is considered to be a neuroendocrine organ since it produces and
releases hormone along with its neural function
autocrines- chemicals that exert their effects on the same cells that secrete them
paracrines- chemicals that act locally but affect cell types other than those releasing the
paracrine chemicals
Chemistry of Hormones
hormones- chemical substances, secreted by cells into the extracellular fluids, that regulate
metabolic function of other cells in the body
-can be classified chemically as either amino acid based or steroids
-long distance chemical signals that travel in blood or lymph throughout the boy
-amino acid based hormones vary from simple amino acid derivatives to peptides to
-steroid hormones are synthesized from cholesterol; only gonadal and adrenocorticol
hormones are steroids
-eicosanoids (leukotrienes and prostaglandins) are biologically active lipids made for
arachidonic acid and are released by nearly all cell membranes
-leukotrienes are signalling chemicals that mediate inflammation and some allergic
-prostaglandins have multiple targets and effects
-since the effects of eicosanoids are typically highly localized, they generally act
as autocrines and paracrines and do not fit the definition of a true hormone
Mechanisms of Hormone Action
-a hormone influences the activity of only certain tissues (target cells)
-hormones alter cell activity (increase or decrease the rates of normal cellular processes)
-hormonal stimulus typically produces one or more of the following changes:
1) alters plasma membrane permeability or membrane potential (or both) by
opening or closing ion channels
2) stimulates synthesis of proteins or regulatory molecules such as enzymes within
the cell
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3) activates or deactivates enzymes
4) induces secretory activity
5) stimulates mitosis
-the level of target cell activation depends on hormone concentration, target cell receptor
content, and affinity of the hormone for the receptor
-water soluble hormones (all amino acid-based hormones except thyroid hormone) act on
receptors in the plasma membrane
-receptors are coupled via regulatory molecules called G proteins to one or more
intracellular second messengers (i.e.: cAMP or calcium) which mediate the target
cell's response
-receptors for water-soluble hormones must be in the plasma membrane since
these hormones cannot enter the cell
-lipid soluble hormones (steroid and thyroid hormones) act on intracellular receptors which
directly activate genes
-receptors for lipid-soluble steroid and thyroid hormones are inside the cell
because these hormones can enter the cell
Plasma Membrane Receptors and Second-Messenger Systems
-all amino acid-based hormones (except thyroid hormone) exert their signalling effects
through intracellular second messengers generated when a hormone binds to a receptor on
the plasma membrane
The Cyclic AMP Signalling Mechanism
-the mechanism involves the interaction of 3 plasma membrane components (a hormone
receptor, a G protein, and an effector enzyme) to determine intracellular levels of cAMP
1) Hormone binds receptor
-the hormone, acting as the first messenger, binds to its receptor on the plasma
2) Receptor activates G protein
-hormone binding causes the receptor protein to change shape which allows it to
bind to a nearby inactive G protein
-the G protein is activated as the guanosine diphosphate (GDP) bound to it is
displaced by the high energy compound guanosine triphosphate (GTP)
-the G protein is inactive when GDP is bound to it
-the G protein is active when GTP is bound to it
3) G protein activates adenylate cyclase
-the activated G protein moves along the membrane and binds to the effector
enzyme, adenylate cyclase
-Gs stimulates adenylate cyclase
-Gi inhibits adenylate cyclase
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-eventually, the GTP bound to the G protein is hydrolyzed to GDP and the G
protein becomes inactive once again
4) Adenylate cyclase converts ATP to cyclic AMP
-as long as Gs is bound to it, adenylate cyclase generates the second messenger
cAMP from ATP
5) Cyclic AMP activates protein kinases
-cAMP, which is free to diffuse throughout the cell, triggers a cascade of
chemical reactions by activating protein kinases
-protein kinases are enzymes that phosphorylate (add phosphate group) to various
-phosphorylation activates some of these proteins and inhibits others, thus, a
variety of processes may be affected in the same target cell at the same time
-the action of cAMP persists only briefly because the molecule is rapidly degraded by the
intracellular enzyme phosphodiesterase
Intracellular Receptors and Direct Gene Activation
-steroid hormones diffuse into their target cells (lipid-soluble) and bind to and activate
intracellular receptors
-the activated receptor-hormone complex makes its way to the nuclear chromatin, where
the hormone receptor binds to a region of DNA (a hormone response element) specific for
-the interaction turns on a gene and prompts transcription of DNA to produce mRNA
-the mRNA is translated on the cytoplasmic ribosomes producing specific protein
-these proteins include enzymes that promote metabolic activities or promote synthesis of
structural proteins or proteins to be exported from the target cell
Target Cell Specificity
-target cell activation by hormone-receptor interaction depends on:
1) blood levels of the hormone
2) relative numbers of receptors for that hormone on or in the target cells
3) affinity (strength) of the binding between the hormone and the receptor
-a large number of high-affinity receptors produces a pronounced hormonal effect
-a smaller number of low-affinity receptors results in reduced target cell response
up-regulation: target cells from more receptors in response to rising blood levels of the
specific hormones to which they respond
down-regulation: prolonged exposure to high hormone concentrations desensitizes the
target cells so that they respond less vigorously to hormonal stimulation
Half-life, Onset, and Duration of Hormone Activity
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