Intracellular Receptors and Direct Gene Action - Online Tutor, Practice Problems & Exam Prep

Steroid hormones, such as estrogen, are lipid-soluble and can pass through cell membranes, allowing them to bind to intracellular receptors. This receptor-hormone complex then enters the nucleus and binds to specific DNA regions, directly influencing gene expression. This process, known as direct gene action, contrasts with amino acid-based hormones that rely on second messenger systems. The effects of steroid hormones are typically slower, taking hours to induce physiological changes, highlighting their role in long-term regulation within the endocrine system.

Actions of Steroid Hormones

When we first introduce hormones, we split them into 2 basic groups based on their chemical structure. We have the amino acid-based hormones, and we have the steroid hormones. Here, we want to talk about the steroid hormones and how they induce change in the cell in more detail. We're going to do that by talking about intracellular receptors and direct gene action. Now before we really dive in, let's just remind ourselves that steroid hormones and also thyroid hormone and that was sort of our one major exception to our hormone groupings.

These hormones can enter the cell membrane, and they can enter the cell membrane because they are lipid soluble. That means that they can pass through that lipid bilayer of the cell membrane. Well, if they can pass through the membrane, that means that the receptor proteins for these hormones are located inside the cell. Remember, this is very different from the majority of amino acid-based hormones, which are stuck on the outside of the cell, which means that the receptor is also going to be on the outside of that cell membrane. Alright.

So let's look at this step by step, but before we do, let's orient ourselves to our image. We have a cell here. We can see the nucleus inside the cell. We see some other things going on there that we'll talk about in a second. We're going to start on the outside with this hormone here, and this is a steroid hormone.

Specifically, this is estrogen, but this is going to apply generally to all steroid hormones. Now remember, in the blood, a steroid hormone is bound to a transport protein because being lipid soluble, it doesn't dissolve in the blood. Now, we don't have that drawn here, but when it gets to the cell, it's going to separate from that transport protein, and we can see that it is going to pass right through the cell membrane. So the first thing we're going to say, step 1: the steroid hormone passes through the membrane. And now this hormone's on the inside of the cell.

And as we follow our arrows here, the next thing we see is this sort of green protein there, and that's supposed to represent the receptor. So this receptor here in the cytoplasm. And we can follow it along, and we can see that our hormone then binds to the receptor, and together, they form what's called the receptor hormone complex. So we're going to say number 2, the hormone inside the cell now binds to a receptor protein. Together, those two things bound together are called the receptor hormone complex.

And if we look at our image here, we can see that this receptor hormone complex next goes into the nucleus. So we're going to say the receptor hormone complex enters the nucleus. Now to be very clear, sometimes that hormone or I'm sorry, that receptor is actually inside the nucleus, and the hormone travels into the nucleus before it forms that receptor hormone complex. Sometimes the receptors are in the cytoplasm; they bind in the cytoplasm and together travel into the nucleus.

Regardless, the hormone receptor hormone complex ends up in the nucleus. And in the nucleus, it is going to bind. We're going to say that this complex binds to a specific DNA region, and we can see that in our image here. This purple molecule represents the DNA, and we see our receptor hormone complex bound to that DNA. And by binding to that DNA, that triggers a cellular response.

Now if binding to DNA is what triggers a cellular response, that means that we are affecting gene expression. This hormone, bound to a protein making that complex, is directly bound to the DNA directly affecting gene expression. That's why we sometimes call this direct gene action. Now again, a reminder, this is very different from those amino acid-based hormones, which are typically stuck on the outside of the cell. So they rely on these second messenger systems to pass the signal along inside the cell.

These steroid hormones, they are in the cell and getting their hands dirty directly in gene expression. Now when I look at this, it also starts to make sense to me a bit more clearly why when we talk about the endocrine system, we say that it works more slowly than, say, the nervous system, which is sort of a rapid signaling system. When I think about these steroid hormones, well, the blood travels to the body relatively quickly, maybe takes a minute or so to get everywhere in the body. But how long does gene expression take? Well, for a steroid hormone to induce a change, you need to wait for RNA to be transcribed.

You need to wait for that RNA to be translated into a protein. You need to wait for that protein to go out and affect physiological change, and sometimes those proteins could last a very long time. So we're talking at the very least many minutes, but typically hours or longer and effects that could last very long times when we're talking about these steroid hormones. Alright. With that, the main thing, though, that you want to take away remember, steroids can enter the cell.

That means that the receptor is inside the cell. It forms that receptor hormone complex, and that receptor hormone complex directly affects gene expression. We'll look at this more in Examples and Practice Problems. I will see you there.

Intracellular Receptors and Direct Gene Action Example 1

In this example, we see an illustration of a cell, and it has different receptors on it. We have purple receptors that are labeled y, and we have green receptors labeled x. The purple receptors, you can see, are on the outside of the cell, on the cell membrane, while the green receptors are in the cell cytoplasm. This example tells us that drawn below is a cell that responds to hormone x and hormone y. The receptors for hormone x are green, while those for hormone y are purple, and we can also see they're labeled with an x and a y.

So, based on this image, we want to conclude the following about the chemical structures of hormone x and y: Let's start with x. The receptors for hormone x are inside the cytoplasm. Which types of hormones have their receptors more often inside the cell cytoplasm? Typically, these are steroid hormones. Therefore, I think hormone x is going to be a steroid. Meanwhile, hormone y, having receptors on the cell surface, suggests that it is more likely to be amino acid-based. There are exceptions to these general rules, but this is the typical categorization.

Next, we discuss which hormone is more likely to be affected by a molecule that inhibits adenylate cyclase. Remember that adenylate cyclase is part of the signaling cascade that involves G protein-coupled receptors, which are found on the cell surface and generally respond to amino acid-based hormones. Therefore, I think the answer here is going to be hormone y.

Lastly, we consider which hormone would be expected to directly interact with the DNA of the cell via a receptor hormone complex. Steroid hormones are known to enter the cell, bind to their receptors forming this complex, and then move into the nucleus—or sometimes the receptors are already in the nucleus—they bind to the DNA and become active in gene regulation. Therefore, hormone x, being a steroid hormone, is expected to directly interact with the DNA of the cell via a receptor hormone complex.

With this information, you have answered our questions about the interactions of hormones x and y with their receptors and cellular mechanisms.

True or False: if false, choose the answer that best corrects the statement.

Steroid hormones are the only hormones that interact with the DNA via a receptor-hormone complex.

• A. True.
• B. False; all hormones can interact with DNA via a receptor-hormone complex; it depends on what type of receptor is used at the target cell.
• C. False; thyroid hormone is an amino-acid based hormone that interacts with DNA via a receptor hormone complex.
• D. False; most peptide hormones interact with the DNA via a receptor complex, while most steroid hormones use second messenger systems.

Which pair of terms below correctly matches the molecule with the pathway?

• A. Intracellular reception: receptor-hormone complex.
• B. Second messenger system: G protein.
• C. Intracellular reception: adenylate cyclase.
• D. A & B are both correct.

Here’s what students ask on this topic:

What are intracellular receptors and how do they function?

Intracellular receptors are proteins located inside the cell, either in the cytoplasm or nucleus. They primarily bind to lipid-soluble hormones like steroid hormones (e.g., estrogen) and thyroid hormones. When these hormones pass through the cell membrane, they bind to the intracellular receptor, forming a receptor-hormone complex. This complex then enters the nucleus and binds to specific DNA regions, directly influencing gene expression. This process, known as direct gene action, leads to the transcription of specific genes into mRNA, which is then translated into proteins that induce physiological changes. This mechanism is slower compared to amino acid-based hormones that use second messenger systems.

How do steroid hormones differ from amino acid-based hormones in their mechanism of action?

Steroid hormones, being lipid-soluble, can pass through the cell membrane and bind to intracellular receptors. This receptor-hormone complex then enters the nucleus and directly influences gene expression by binding to specific DNA regions. This process is known as direct gene action. In contrast, amino acid-based hormones are not lipid-soluble and cannot pass through the cell membrane. Instead, they bind to receptors on the cell surface, triggering a cascade of intracellular events through second messenger systems. This indirect mechanism is generally faster but does not directly alter gene expression.

Why do the effects of steroid hormones take longer to manifest compared to amino acid-based hormones?

The effects of steroid hormones take longer to manifest because they involve direct gene action. After the hormone binds to its intracellular receptor, the receptor-hormone complex enters the nucleus and binds to specific DNA regions, initiating the transcription of genes into mRNA. This mRNA is then translated into proteins, which induce physiological changes. This entire process—from gene transcription to protein synthesis and subsequent physiological effects—takes time, often hours or longer. In contrast, amino acid-based hormones act through second messenger systems, which can rapidly amplify the signal and produce quicker responses.

What is the receptor-hormone complex and what role does it play in gene expression?

The receptor-hormone complex is formed when a lipid-soluble hormone, such as a steroid hormone, binds to its intracellular receptor. This complex then enters the nucleus and binds to specific DNA regions. By binding to these DNA regions, the receptor-hormone complex directly influences gene expression. It initiates the transcription of specific genes into mRNA, which is then translated into proteins. These proteins go on to induce various physiological changes in the cell. This direct interaction with DNA is why this process is referred to as direct gene action.

How does the lipid solubility of steroid hormones affect their mechanism of action?

The lipid solubility of steroid hormones allows them to pass through the lipid bilayer of the cell membrane. Once inside the cell, they bind to intracellular receptors, forming a receptor-hormone complex. This complex then enters the nucleus and binds to specific DNA regions, directly influencing gene expression. This ability to cross the cell membrane and directly interact with DNA is a key feature that distinguishes steroid hormones from amino acid-based hormones, which cannot pass through the cell membrane and must rely on cell surface receptors and second messenger systems.