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The essence of multicellularity is the coordinated
interaction of the various kinds of cells that make up the body.
Cells communicate with each other by chemical signals.
Three kinds of chemical signaling can be distinguished: |
autocrine:
the cell signals itself through a chemical that it synthesizes and then
responds to. Autocrine signaling can occur solely within the
cytoplasm of the cell or by a secreted chemical interacting with
receptors on the surface of the same cell |
paracrine:
chemical signals that diffuse into the area and interact with
receptors on nearby cells. |
| Examples are: |
| - The release of cytokines that cause
an inflammatory response in the area. |
| - The release of neurotransmitters at
synapses in the nervous system. |
endocrine:
the chemicals are secreted into the blood and carried by blood and
tissue fluids to the cells they act upon. |
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| Kinds of Hormones |
| There are two major classes of hormones - proteins,
peptides, and modified amino acids steroids.
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 These hydrophilic (and mostly large) hormone
molecules bind to receptors on the surface of "target"
cells; that is, cells able to respond to the presence of the hormone.
These receptors are transmembrane proteins. Binding of the hormone to
its receptor initiates a sequence of intracellular signals that may
alter the behavior of the cell (such as by opening or closing
membrane channels) or stimulate (or repress) gene expression in the
nucleus by turning on (or off) the promoters and enhancers of the
genes.
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| This is the sequence of
events: |
| The hormone binds to a site on the extracellular
portion of the receptor. |
| The receptors are transmembrane proteins. |
| Many (but not all) pass through the plasma membrane 7
times, with their N-terminal exposed at the exterior of the cell and
their C-terminal projecting into the cytoplasm. |
| Binding of the hormone to the receptor activates a G
protein associated with the cytoplasmic C-terminal. |
| This initiates the production of a "second
messenger". The most common of these are cyclic AMP, (cAMP)which
is produced by adenylyl cyclase from ATP (shown here), and inositol
1,4,5-trisphosphate (IP3) |
| The second messenger, in turn, initiates a series of
intracellular events (shown here as short arrows) such as ?
phosphorylation and activation of enzymes release of Ca2+ stores
within the cytoplasm. |
| In the case of cAMP, these enzymatic changes activate
the transcription factor CREB (cAMP response element binding protein) |
Bound to its response element 5' TGACGTCA 3'
in the promoters of genes that are able to respond to the hormone,
activated CREB turns on gene transcription. |
The cell begins to produce the appropriate gene
products in response to the hormonal signal it had received at its
surface.
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| Steroid Hormones |
Steroid
hormones, being hydrophobic molecules, diffuse freely into all cells.
However, their "target" cells contain cytoplasmic and/or nuclear
proteins that serve as receptors of the hormone. The hormone binds to
the receptor and the complex binds to hormone response elements -
stretches of DNA within the promoters of genes responsive to the
hormone. The hormone/receptor complex acts as a transcription factor
turning target genes "on" (or "off")
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| Hormone Regulation |
| The levels of hormones circulating in the blood are
tightly controlled by three homeostatic mechanisms: |
| When one hormone stimulates the production of a
second, the second suppresses the production of the first. |
| Example: The
follicle stimulating hormone (FSH) stimulates the release of
estrogens from the ovarian follicle. A high level of estrogen, in
turn, suppresses the further production of FSH. Antagonistic pairs of
hormones. |
| Example: Insulin
causes the level of blood sugar (glucose) to drop when it has risen.
Glucagon causes it to rise when it has fallen. Hormone secretion is
increased (or decreased) by the same substance whose level is
decreased (or increased) by the hormone. |
Example: a rising
level of Ca2+ in the blood suppresses the production of the
parathyroid hormone (PTH). A low level of Ca2+ stimulates it.
Hormone Transport - Although a few hormones circulate simply
dissolved in the blood, most are carried in the blood bound to plasma
proteins. For example, all the steroid hormones, being highly
hydrophobic, are transported bound to plasma proteins.
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