Target Cell Activation

HormoneBy definition, hormones are chemical messengers that travel throughout the body in the blood. It follows to reason that everywhere the blood goes, hormones also go, and so hormones have the ability to interact with nearly every cell in the body as it is the rare cell that is able to live with no nourishment received from or waste products eliminated by the blood. How, then, is it possible for all of the circulating hormones to not cause massive upheaval and wreak havoc on the human body’s delicate balancing act of homeostasis? If all hormones rub against all cells, then why does not prolactin cause the bone cells in our patella to lactate, or parathyroid hormone cause the muscle cells in our palmaris longus to release calcium ions? Hormones are able to circulate freely in the human blood because of three primary reasons, which are target cell specificity, hormone interactions, and target-receptor interaction.

The first factor that should be examined is target cell specificity. Just as with so many other reactions in the human body, for an interaction to occur, both the first messenger and the receptor must have the ability to interact with one another. The bone cells in a patella are not the mammary glands in the breast, and so do not receptors that would allow prolactin to cause lactation; muscle cells in the palmaris longus do not have the osteoclasts that release calcium ions and so do not have receptors that would allow parathyroid hormone to cause calcium ion release. If a cell does not have receptors for a hormone, it cannot be a target cell. If, however, the cell does have receptors which allow it to be targeted by a specific hormone, there are three additional factors that must be considered when examining hormonal effects. First, there must be a level of the hormone circulating in the blood in an amount sufficient to cause a reaction. Much like a single drop of white paint in a five-gallon pail of black paint will not create grey paint, a single hormone of insulin will not lower blood sugar levels by any significant amount. Second, there must be an amount of hormone receptors on the target cell in a number great enough to allow the hormone to cause a reaction. Much as a single air vent in a 3,000 foot house will not allow for sufficient cooling by even the best of air conditioners in Arizona, a single receptor on a target cell may not allow for a complete cellular reaction. Finally, there must be sufficient affinity between the hormone and the receptor for a reaction to occur. Just as a single second of loud music often will not awake us from a deep sleep, a too-brief interaction time between a hormone and a receptor may not allow for a second-messenger to be produced or an mRNA to be transcribed. Although it is a general rule that more is better – more hormone, more receptors, more affinity will create more cellular response – more is not always required – a mother can hear the first yelp of cry hurt child from across the playground, and some hormones provoke immediate and great responses through amplification.

Target Cell ActivationThe second factor – hormonal interactions – refers to how one hormone affects another hormone within the body as a whole and within individual cells. There are three types of hormonal interactions. The first hormonal interaction is called permissiveness; this occurs when one hormone requires the presence of another specific hormone for its full effect to occur, much as 3D glasses are needed to experience the full effect of a 3D movie. An example of this is follicle-stimulating hormone which causes the female to produce an egg and luteinizing hormone that causes ovulation of the egg. The second hormonal interaction is called synergism; this occurs when the combined effect of two hormones is greater than the sum of the two effects individually, much as a little bit of flour and a little bit of sugar are needed to create delicious cookies. An example of this is the protein synthesis caused by both growth hormone and insulin, or the increased blood glucose levels caused by both glucagons and growth hormone. The third hormonal interaction is called antagonism; this occurs when two hormones are present that work in opposing ways, much as gravity pulls water down towards a plant’s roots while the intramolecular strength of its hydrogen bonds pull it up to the leaves for evaporation. An example of antagonistic hormones are the blood calcium regulating hormones calcitonin and parathyroid hormone.

The third factor – target-receptor interaction – is what causes the final cellular response to the hormone. There are five possible cell responses to a hormone, and a single cell may respond in more than one way to the same hormone. These responses include the following: alteration of plasma membrane permeability or potential; protein synthesis; enzyme activation or deactivation; secretion induction; cellular mitosis. Where this interaction occurs depends on whether or not the hormone is water- or lipid-soluble. Water-soluble hormones are not able to permeate the phospholipid bilayer of the cellular membrane, and so must interact with their receptors at the plasma membrane. Once the water-soluble hormone, which acts as a first messenger, binds to its receptor, an attached G protein will change shape as it is activated by GTP displacing GDP on its alpha subunit, and it will detach from the receptor molecule. From this point, there are two possible reaction cascades that may occur, using cyclic AMP as a second messenger or using intracellular calcium ions as the final messenger. In the cyclic AMP signaling mechanism, the activated G protein will then bind to the enzyme adenylate cyclase and either, as Gs, stimulate it to generate cyclic AMP (cAMP) from ATP or, as Gi, inhibit it from generating cAMP. The cAMP will travel in the cytoplasm to activate protein kinase A, which will then phosphorylate other proteins causing a variety of cell reactions. Because each adenylate cyclase enzyme is able to generate multiple cAMP molecules, a single hormone-receptor interaction can lead to a large number of intracellular reactions, an event called amplification. This amplification is kept under relatively tight control by the rapid degradation of cAMP by the enzyme phosphodiesterase, so that a single hormone-receptor interaction does not create a too-large cellular reaction. In the second route, the activated G protein will bind to phospholipase C rather than adenylate cyclase. Phospholipase C will then travel along the plasma membrane to cleave phosphatidyl inositol bisphosphate (PIP) into diacylglycerol (DAG) and inositol triphosphate (IP3). DAG serves as a second messenger as it activated protein kinase C to phosphorylate various proteins. IP3 acts as a second messenger to cause a release of calcium ions from the endoplasmic reticulum. The calcium ions are then free to either to directly interact with other intracellular enzymes or to bind to the protein calmodulin and then activate other enzymes. In either reaction, cAMP or PIP, the activated G protein will become inactive when the GTP is hydrolyzed back to GDP when the hormone detaches from the receptor, and the inactive G protein will re-bind to the receptor in the plasma membrane.

Hormone ReceptorLipid-soluble hormones are able to permeate the phospholipid bilayer of the cellular membrane, and so are able to interact with receptors in the cell’s cytoplasm. Once the lipid-soluble hormone binds to the intracellular receptor, the receptor’s chaperone is detached and the hormone-receptor complex will move into the cell nucleus where it acts as a transcription factor. Here, it will bind to a specific region on the DNA strand called the hormone response element. A unique exception to this intracellular movement occurs with thyroid hormone, whose receptors are always attached to DNA. This coupling of the hormone-receptor complex to the DNA strand will cause transcription of a messenger RNA inside the cell nucleus, which will then be translated by ribosomal RNA in the cytoplasm to produce a specific protein, which may be an enzyme, a structural protein, or a secretory protein.   Hormone and Target Cell

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One thought on “Target Cell Activation

  1. Greetings! Very helpful advice within this article! It is the little changes that produce the biggest changes. Thanks a lot for sharing!|

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