So as I noted earlier, not all signaling
systems work through membrane receptors.
Some examples of those that work internal to the cell -
the steroid hormone receptor which works by the process
of a steroid hormone diffusing its way across the
membrane ultimately to the receptor in the cytoplasm.
The thyroid hormone receptor also
works in a fashion as I will describe
here through the transport system
that gets things into the nucleus.
Vitamin D has a little bit
different route that it gets there.
It gets into the cell not through
the receptor but through action
of a vitamin D transport protein
that grabs the vitamin D and the cell
membrane and then transports it to
the receptor in the cytoplasm, where
that then takes the vitamin D into
the nucleus to exert its effects.
And at last the retinoic acid/retinoid
receptor has a transport system that also
gets retinoic acid ultimately into the
nucleus for controlling gene expression.
Each of these nuclear hormone receptors
is depicted schematically here.
They have an N-terminal region that’s shown on the
left and a C-terminal region that’s shown on the right.
And that N-terminal region has a DNA binding domain that is
specific to binding a specific sequence within a DNA molecule.
Another part of the protein has a ligand binding domain,
that’s the part that binds to the receptor hormone.
It is the binding of that receptor
hormone that causes the overall
receptor to exert the control on
gene expression that it controls.
So these receptor hormones bind to
specific sequences in DNA molecules as
I said, that are known as hormone
response elements that occur in the DNA.
And these are specific for each of the individual
transcription factors that I’ve described here.
Now nuclear hormone signaling helps to control
processes of metabolism, inflammation, immune
function, water and salt balance, sexual
characteristics and response to illness and injury.
That’s a pretty wide variety of things that’s
needed for a body to be able to respond to.
Steroid signaling uses intracellular
non-membrane receptors as I’ve noted.
There are five classes of steroid receptors that are broken
down into two groups - the corticosteroids and the sex hormones.
Signaling mostly affects the gene
expression so it tends to be much
slower in its effects than those
processes that affect enzyme activities.
So let’s look at the process of steroid
signaling going on in the cell.
Steroid hormone is released into the
blood, that’s the first messenger.
And it travels to its target.
At its target it crosses the lipid bilayer of the
target cell without interaction of other proteins.
Inside the cytoplasm it binds
to an internal receptor.
And that internal receptor has its shape
changed as a result of binding of the hormone.
This converts the receptor into what’s
known as a transcription factor.
The transcription factor goes into the nucleus and binds to the
hormone response element in the
DNA, affecting its transcription.
So the movement of the transcription factor into
the nucleus with the hormone bound to it causes a
different set of genes to be made than was being made
before the receptor protein went into the nucleus.
So this is shown schematically in
the figure I’m showing you here.
We see for example a cell,
shown as a rectangle in grey.
We see inside of it, a receptor protein that’s
bound to another molecule and we see the nucleus.
So here’s the phospholipid
bilayer that surrounds that cell.
And there is the receptor bound
to a protein known as Hsp70.
Now Hsp stands for
heat shock protein 70.
And heat shock proteins have quite a variety of
functions, but one of the functions the heat shock
protein 70 has here is that it’s preventing the
receptor protein from going into the nucleus.
It’s keeping it in the cytoplasm.
Well here’s the steroid hormone that
arrives in the blood, it crosses
the lipid bilayer on its own, it
interacts with the receptor protein.
And binding of the hormone to the receptor protein
causes the receptor protein to let go of Hsp70.
Well since Hsp70 was what was keeping
the protein from going into the
nucleus, the protein that is the
receptor carrying the steroid hormone
now moves into the nucleus and goes
and activates transcription of
genes that have hormone response
elements that are linked to them.
In this way, the gene expression
of the cell has been changed.