00:00 So now let's take a closer look at how hormones activate genes. Since they cannot go directly into the cell because they're not lipid-based, amino acid-based hormones, except for our thyroid hormone, are going to exert their effects through something called second messengers. There are 2 main types of second messenger systems that we find in our cells. 00:32 The 1st second messenger is going to be cyclic AMP. The 2nd is the PIP₂ calcium second messenger system. If we take a closer look at the cyclic AMP signaling mechanism, we find that first our messenger is going to bind to the receptor on the target cell. So the messenger in this case is the hormone. Binding of this hormone to the receptor is going to activate a G protein since this receptor is usually something called a G protein-coupled receptor. Once the G protein is active, it's going to activate or inhibit other enzymes known as the adenylate cyclase. The adenylate cyclase is then going to convert ATP in the cell to the 2nd messenger which is cyclic AMP. Cyclic AMP can then go on to activate other proteins known as protein kinases. These are enzymes that are going to phosphorylate or add a phosphate to other proteins. This usually happens in a signal transduction pathway or kind of like a relay where each message is going to be passed from one molecule to the next until we get to our actual target activity. The phosphorylated proteins are then going to be activated or inactivated. 02:12 The cyclic AMP is then rapidly degraded by another enzyme that's pretty much the opposite of a protein kinase known as a phosphodiesterease. This is going to stop that signal transduction pathway cascade. Cascades have the ability to have huge amplification effects and so the second messenger system allows for 1 hormone signal to cause a very big effect in our target cell. The 2nd second messenger system that we find in our cells is the PIP₂ calcium signaling mechanism. In this mechanism, a hormone is going to bind to a G-coupled protein receptor in the membrane of the target cell and this is going to activate a G protein that is going to then activate a different effector enzyme known as phospholipase C. This activated phospholipase C is then going to split the membrane protein PIP₂ into 2 different second messengers. The 1st is diacylglycerol or DAG which is going to activate protein kinases which can subsequently phosphorylate proteins. The 2nd is inositol trisphosphate or IP₃. This is going to cause calcium to be released from intracellular stored sites inside of the cell. 03:51 The calcium is then going to act as another second messenger or a 2nd second messenger. 03:59 The calcium alters the enzyme activity and channels or it binds to regulatory proteins such as calmodulin. Once calcium is bound to calmodulin, this is going to activate enzymes which will then amplify the cellular response. So now that we have discussed how second messengers work, let's take a closer look at how genes are activated by these proteins. Lipid-soluble steroid hormones and thyroid hormone can actually diffuse directly into the target cell and bind to receptors inside of the cell or your intracellular receptors. From here, they make a receptor hormone complex that enters the nucleus and then binds to a specific region of the DNA inside the nucleus. From there, this initiates DNA transcription to produce our mRNAs. 05:05 Once the mRNA is produced, it is then translated into specific proteins in the cytoplasm of that cell. Proteins that are synthesized have various functions including things like inducing metabolic activity or creating structures or being exported or secreted from the cell.
The lecture Pathways of Hormone Action (Nursing) by Jasmine Clark, PhD is from the course Endocrine System – Physiology (Nursing).
Why do most amino acid-based hormones exert their effects through second-messenger systems?
When a hormone binds to a receptor and activates a G protein, how is the cyclic adenosine monophosphate (cAMP) second messenger system activated?
In the PIP2 (phosphatidylinositol biphosphate)-calcium signaling mechanism, how do calcium ions act as a second messenger?
In order for a receptor-hormone complex to bind to a specific region of the DNA, what needs to occur first?
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