Homeostasis: Can Live With It, Can’t Live Without It
Jim Jimmy has an average resting heart rate of 60 beats per minute (bpm) and an average heart rate of 140 bpm when jogging. His resting and exercising heart rates are different because his body’s demand for oxygen changes when exercising. If his heart rate remained at 60 bpm when exercising, his muscles would not receive enough oxygen to function. In other words, his increase in heart rate during exercise is necessary for physiological processes to work, called homeostasis. Homeostasis is not a static process – i.e., the body must maintain a constant internal temperature of 37 degrees Celsius (98.6 degrees Fahrenheit). If our physiology were fixed, our heart and respiratory rates would remain stable, even during exercise. In reality, our internal and external environments are in constant flux, so the body is constantly adjusting set points[ref]A homeostatic set point is an adjustment to the homeostasis to retain or regain stability[/ref] to maintain homeostasis. Let’s look at Jim Jimmy’s example again.
Disease can affect multiple homeostatic mechanisms, which prevents your body from establishing the proper set points, resulting in homeostatic imbalance (illness). Once you are well, homeostasis resumes. If a homeostatic set point does not return to normal, this is a chronic disease – e.g., Type 1 diabetes. Death is the complete loss of homeostasis and the cover art of most Slayer albums.
What are Hormones?
Cells don’t have cellphones (ha, ha, ha), so they need to communicate the old-fashioned way of sending physical messages.
What are these messages?
They’re hormones, the body’s chemical messengers.
Who receives the hormone message?
Target cells that have the matching internal or external receptor protein.
An endocrine gland[ref] is an organ whose primary function is to secrete hormones directly into the blood via exocytosis (proteins are too large to fit through transport proteins). For example, the pituitary gland’s primary function is to secrete the nine master hormones into the blood. Exocrine glands secrete substances into ducts and travel to an open space, such as the skin’s surface.
A lot of organs have both endocrine and exocrine functions. For example, the pancreas’s endocrine function is the secretion of insulin and glucagon hormones, which regulate the amount of sugar in the blood.
The pancreas also makes most digestive enzymes, which it secretes into a duct that leads to the small intestine. The kidneys even secrete hormones, but it is not an endocrine gland because their primary function is not endocrine. In other words, whether an organ is an endocrine gland is arbitrary. What matters is the message the hormone brings to its target cell and the cellular response that follows.
| This is Insulin Attaching to its Target Cell | This is Gold Five Telling Red Five To Stay on Target |
 |  |
Non-Steroid Hormones vs. Steroids Hormones
Non-steroid hormones are water-soluble, protein-based hormones that cannot diffuse through the cell membrane. Protein-based hormones are too large to fit through channel proteins. When a non-steroid hormone attaches to the matching receptor protein on its target cell, it initiates a fast and short-lived cellular response. Insulin is an example of a non-steroid hormone. When insulin attaches to a receptor protein on a muscle fiber, it starts a cellular response that opens glucose channel proteins.
Steroid hormones, or steroids, are derived from cholesterol and are lipid-soluble; therefore, steroids can diffuse through the phospholipid bilayer. Steroids are slow-acting hormones, but their effect on their target cell is long-lived. Testosterone and estrogen are examples of steroids.
Steroids travel to their target hormones via the blood; however, steroids (nonpolar) and blood plasma (polar) cannot form a solution. Once a steroid diffuses out of its parent cell, it attaches to a protein carrier and becomes water-soluble. The protein carrier acts as an Uber and transports the steroid to its target cell. At the target cell, the steroid detaches from the protein and diffuses into the cell. Once in the cell, the steroid binds to another receptor protein and becomes the hormone-receptor complex (HRC). The HRC enters the nucleus and binds to DNA, which begins protein synthesis.
| This is a Non-Steroid Hormone Response | This is a Steroid Hormone Response | This is a Screaming Hairy Armadillo |
 |  |  |
Receptor Protein Regulation: Protein Goes Up. Protein Goes down.
Cells can gain and lose the quantity of cell membrane receptor proteins based on the need for a non-steroid hormone. If too much insulin is in the blood, insulin’s target cells will reduce the cell membrane’s number of receptor proteins. The reduction in membrane receptor proteins is called downregulation, and cells do this to prevent being overstimulated by a non-steroid hormone. If a person’s blood sugar spikes after a meal and there is insufficient insulin in the blood, then insulin’s target cells will increase the plasma membrane’s number of receptor proteins. The escalation in receptor proteins is called upregulation, and cells do this to increase exposure to a hormone.
| This is Upregulation and Downregulation | This is Homer Making His Bed Go Up and Down |
|---|---|
 |  |
Synergism and Permissiveness and Antagonism, Oh My!
Most target cells receive stimulation from multiple hormones because they have different receptor proteins embedded in their plasma membranes. Stimulation from several hormones leads to three primary effects:
- Stronger response
- Activation of a response
- Opposing response
Synergism occurs when two or more hormones work together to produce a more significant cellular response. Glucagon, epinephrine, and cortisol independently stimulate the release of glucose from liver cells; however, when all three hormones stimulate a liver cell simultaneously, the cell will release copious amounts of glucose.
Permissiveness happens when a hormone needs another to produce an active cellular response. Epinephrine is one of the hormones involved in the catabolism (breakdown) of lipids (lipolysis) in adipocytes. However, on its own, epinephrine has almost no effect on lipolysis because of the limited number of epinephrine receptor proteins on the adipocyte membrane. Thyroid hormone stimulates the upregulation of epinephrine receptors on the plasma membrane of adipocytes. The surge in epinephrine receptors will increase epinephrine’s action, resulting in lipid catabolism.
The pancreas secretes insulin, which tells liver cells to remove glucose from the blood. The pancreas also secretes glucagon that initiates the release of glucose from liver cells. Insulin and glucagon are antagonists to one another because they have an opposite effect on their target cells.
| This is Synergism | This is Permissiveness | This is Antagonism |
|---|---|---|
 The two blue lines show synergism because the combination of hormones greatly increases their effect | Cortisol is a permissive hormone because, by itself, it has little effect on blood sugar. However, it becomes effective when combined with glucagon and epinephrine. |
Negative and Positive Feedback
Negative feedback loops are the primary mechanisms the body uses to maintain homeostasis. When you are hyperglycemic, insulin secretion increases resulting in decreasing blood sugar. When you are hypoglycemic, glucagon secretion surges, increasing blood sugar. The antagonistic effects between insulin and glucagon ensure that your blood sugar remains within at a homeostatic level.
When negative feedback faults, homeostasis is lost. For example, a type 1 diabetic’s immune system destroys the cells that make insulin. Without insulin, sugar remains in the blood, and the target cells begin to stave, leading to hypoglycemia. If a person with diabetes does not receive insulin injections, the starving cells will die, resulting in organ failure and death.
Positive feedback loops are activated when the body needs more than normal homeostatic levels. For the first nine months of pregnancy, the placenta releases the hormone progesterone, which prevents the uterus from contracting. When a woman goes into labor, progesterone levels drop, and oxytocin (hormone) levels surge. The surge in oxytocin stimulates labor contractions, and the increase in labor contractions will accelerate the rate of oxytocin secretion. Labor contractions and oxytocin levels will continue to rise until the child’s birth.
| This is Negative Feedback | This is Positive Feedback | This is Your Physiology Teacher Listening to Nickleback |
|---|---|---|
 |  |  |
The Hypothalamus and its Sidekick the Pituitary Gland: We Control the Homeostasis
The hypothalamus is a region in the brain that controls the body’s primary homeostatic and behavioral functions. Body temperature, master hormones production and secretion, emotional response, sleep-wake cycle, water balance, hunger, thirst, libido, muscle mass, mammary gland development, labor, menstruation, metabolism, and reproduction are primarily under the control of the hypothalamus. If there is a hormonal response in the body, then the hypothalamus is most likely directly or indirectly involved.
The pituitary gland is under the hypothalamus’s control and stores the eight master hormones that target most of the body’s endocrine glands. (There are nine master hormones, but one is often not discussed.)
| These are the Master Hormones | These are Jedi Masters |
|---|---|
 |  |