5.5Coordination between the Nervous and Endocrine Systems

This section provides several examples to explain how an animal’s internal environment is maintained constant by coordination between the nervous and endocrine systems.


Feedback Regulation

Certain engineering concepts, represented by biocybernetics, are important for explaining the structures playing a vital role in homeostasis. The school of thought that presents an organism as a single system composed of regulatory and information transmission systems was established in 1940 by Norbert Wiener as a regular joint seminar with the Massachusetts Institute of Technology and the medical department of Harvard University. According to him, if the biological regulatory system is believed to be a closed loop comprising operating parts, controlled targets, and detecting parts, then it is stabilized by a feedback loop. An intuitive example is the system where a heater (the operating part) provided with a temperature sensor maintains room temperature (the amount to be controlled) constant. Changes in the temperature, which is the amount to be controlled, are received by a bimetal-like sensor and regulated using negative feedback in a direction that mitigates the change.

Column Fig. 5-2 Negative Feedback Regulation of the Hypothalamus, Pituitary Gland, and Thyroid Gland

Solid lines represent promotion and dotted lines represent suppression.

Feedback regulation in the body can be explained using the example of the mechanism for maintaining thyroxine concentration (the amount to be controlled) constant in the blood plasma. The simplest system is one where a negative feedback circuit detects thyroxine concentration using receptors found in the thyroid gland, which is a part of the endocrine system, to regulate the production and secretion of thyroxine (promoting thyroxine secretion when its concentration is low and inhibiting secretion when its concentration is high) (Column Fig. 5-2). However, an organism is much more complicated. Thyroxine secretion is positively controlled by thyrotropin secreted from the upper pituitary gland, and thyrotropin secretion is positively controlled by the thyrotropin-releasing hormone secreted from the upper hypothalamus. Therefore, thyroxine secretion experiences negative feedback regulation for the hypothalamus and pituitary gland in order to regulate its own concentration in the blood plasma with small fluctuations.

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Homeostasis of Body Temperature

Animals have two methods of responding to fluctuations in the external temperature. The group called “ectotherms,” which includes all invertebrates as well as some vertebrates such as fish, amphibians, and reptiles, have a particular mechanism to adjust to the changes in the external environment. On land, where there are large variations in temperature, fluctuations in body temperature are mitigated by behavioral mechanisms such as escaping to a hole dug in the ground or moving to a place with sunshine. The other group called “endotherms” includes organisms that maintain their body temperature almost constant despite the changes in the external temperature. Animals and birds fall under this category. These animals were previously called “poikilotherms” and “homeotherms” because attention was only paid to the changes in body temperature. However, there is only a thin line between these two groups, and therefore, the terms endotherm and ectotherm are currently used with emphasis on the heat source.

Of the endotherms that maintain homeostasis of body temperature, animals such as polar bears and penguins living at the poles and whales or seals that migrate to the polar oceans control changes in core body temperature using feathers or subcutaneous fat, which are very effective in providing insulation. These animals generate heat by burning accumulated body fat.

In humans, the sympathetic nervous system is the first to be stimulated by reduction in the external temperature; goose bumps appear and loss of heat through hair roots is prevented, while heat is generated by shivering due to the contraction of the skeletal muscles. Furthermore, in response to even slight reduction in body temperature, secretion of the thyroid hormone (thyroxine) is promoted by the hypothalamus, pituitary, and thyroid systems (See column Fig. 5-2); thyroxine acts on various tissues to increase oxygen consumption and elevate the metabolic rate and heat production in each tissue. In all vertebrates, removal of the thyroid gland leads to a significant decline in oxygen consumption and basic metabolism. Even in endotherms, thyroid function declines and reductions in body temperature are observed during hibernation. Hormones promoting metabolism include catecholamine (adrenaline) and glucocorticoid; however, thyroxine is necessary for these hormones to express their effects. This is referred to as a permissive action of thyroxine. Thus, when the external temperature decreases, the nervous and endocrine systems function together to prevent the loss of heat and promote heat production.

On the other hand, the only method to counteract an increase in the external temperature is to lower the body temperature by perspiration, which uses the high vaporization heat of water. Perspiration is caused by stimulation of the sympathetic nervous system; however, regulation by hormones cannot be negated. As will be explained in the next section, the volume of sweat secreted after strenuous exercise is much higher after consumption of fresh water than after consumption of isotonic fluids; vasopressin, which is an antidiuretic hormone, might control this phenomenon.

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Homeostasis of Body Fluids

Responses to the environment and homeostasis of body fluids have already been described using the example of migratory fish. Here we have explained the mechanism of regulation by the complexly intertwined nerves and hormones, using the regulation of bodily fluids in humans as an example, which is constantly being researched. When the influx and outflux of water and ions are examined in terrestrial animals, the entrance is ingestion through the mouth, followed by absorption into the intestines, and then the exit through either respiration, sweat, or discharge as urine. However, because the regulation of respiration and sweat is very difficult, ingestion through the mouth and excretion through kidneys are tasked with homeostasis regulation.

Let us consider how the balance of body fluids fluctuates after a marathon and how it is regulated back to recovery. Immediately after a marathon, because water is lost through respiration and both water and ions are lost through sweat, the osmotic pressure in blood plasma is elevated and there is a loss in blood volume. These changes are sensed by osmotic pressure receptors in the hypothalamus and by capacity receptors (stretch receptors) in the atria, which incite thirst (for the act of drinking water). At the same time, vasopressin is secreted, and urination is almost completely stopped because water is reabsorbed by the kidneys (Fig. 5-6). Moreover, renin is secreted from the kidneys because of reduction in blood volume and activation of the sympathetic nervous system; this enzyme produces angiotensin II in the blood. This hormone induces thirst using the central nervous system and promotes vasopressin secretion. On the other hand, secretion of the atrial natriuretic peptide (ANP) from the atria is inhibited because of reduction in blood volume (Fig. 5-6). Because ANP has a diuretic effect and inhibits vasopressin secretion, reduction in ANP is antidiuretic and also increases thirst. The increase in angiotensin II and decrease in ANP promote secretion of aldosterone, which is a hormone that protects Na+ from the adrenal cortex. Because Na+ is lost through sweat, not only water but also Na+ must be recovered. Aldosterone also promotes Na+ reabsorption in the kidneys. Furthermore, angiotensin II promotes Na+ ingestion by causing a sodium appetite. Thus, the lost water and Na+ are returned to normal levels as a result of the coordination of the nervous and endocrine systems, and blood volume is restored. The fact that it is necessary to ingest not only water but also Na+ at the same time can be clearly understood from the fact that osmotic pressure decreases and vasopressin secretion is inhibited when pure water is drunk. The ingested water is then discharged as urine or sweat. In such a case, isotonic beverages containing ions are very effective.

Fig. 5-6 Coordination of the Body Fluid Regulating Systems occurring after a Marathon

Here, attention is paid only to changes in blood volume in order to avoid complexity. Solid lines indicate promotion and dotted lines indicate suppression, while the thickness of the lines indicates the strength of the effect. ANP inhibits ingestion behavior and any action in the intestines, promoting discharge in the kidneys, but secretion is inhibited and indicates the reverse effect. ANG II, angiotensin II; ANP, atrial natriuretic peptide.


Role of Blood Plasma Proteins

Plasma proteins such as albumin and globulin can be dissolved in 1 mL of plasma at a volume in excess of 60 mg. Blood plasma proteins bind to various foreign bodies introduced into the body (into the blood) through organs that are in contact with the external envirnoment, such as the skin, digestive system, and respiratory system, and they prevent these bodies from exiting the blood vessel and causing harm to cells. The inner surface of blood vessels is lined with endothelial cells. Slight fenestrations are present between the endothelial cells through which many inorganic ions (such as Na+ or Cl) and low-molecular-weight substances can pass. However, plasma proteins have a high molecular weight (60,000–10,000) and cannot pass through these fenestrations (Column Fig. 5-3). As a result, plasma proteins are not found in the intercellular fluid. These proteins act as amphoteric ions having a large charge and have a buffering effect that mitigates pH changes in the extracellular fluid.

The osmotic pressure in plasma is slightly higher than that in the intercellular fluid because of the presence of plasma proteins. This difference in osmotic pressure pushes water into the blood vessel through the intercellular gaps in the endothelial cells. However, because the blood pressure in blood vessels is greater than the intercellular pressure, a balance is achieved with the force of water being pushed out from the blood vessels (Column Fig. 5-3). In nephritis, this balance is broken by the loss of plasma proteins in urine and the plasma from which protein has been removed by blood pressure and pushed to the outside of the blood vessel causes edema. Children in famine-affected areas in Africa are often seen in photographs with greatly distended stomachs; this is because plasma proteins are reduced as a result of malnutrition and because the water in plasma leaves the blood vessels and accumulates in the abdominal cavity. Edema from excessive dieting is also caused by the same reasons.

Column Fig. 5-3 Water and Ion Transfer inside and outside the Blood Vessel

To prevent the exit of plasma proteins from the blood vessel, osmotic pressure must be slightly higher in the plasma than in the intercellular fluid. Water is brought into the blood vessel because of this difference in osmotic pressure, but blood pressure within the blood vessel achieves a balance.

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Homeostasis of Blood Glucose Levels

Energy metabolism in animal cells is primarily regulated according to glucose levels, and the blood glucose level is carefully maintained within a suitable range. Blood glucose levels are regulated by glucose supplied by absorption in the intestines, gluconeogenesis and glycogenolysis in the liver, and glucose consumption in the liver, skeletal muscles, and fatty tissues.

When the blood glucose level is lowered, neurons of the hunger center in the hypothalamus are activated to arouse hunger (Fig. 5-7). Furthermore, the sympathetic nervous system is activated, and thus, glucagon is secreted from the pancreatic α cells, while adrenaline is secreted from the adrenal medulla. α cells also occasionally directly react to reduction in the blood glucose level. Reduction in the blood glucose level also promotes secretion of ACTH and the growth hormone from the pituitary gland through the hypothalamus. ACTH acts on the adrenal cortex to promote glucocorticoid secretion (cortisol in humans). Hyperglycemic hormones such as glucagon, adrenalin, cortisol, and the growth hormone act on the muscles and liver to promote glycogen decomposition and also inhibit glucose infiltration into the heart and muscles, which are organs that consume glucose.

Fig. 5-7 Interactions between the Autonomic Nervous System and Endocrine System in Blood Glucose Regulation

ACTH, adrenocorticotropic hormone / AD, adrenaline, GH, growth hormone

When blood glucose levels are elevated, the satiety center of the hypothalamus is excited and appetite is suppressed (Fig. 5-7). The parasympathetic nervous system is also activated such that insulin is secreted from the pancreatic β cells. At the same time, the β cells directly detect the increase in blood glucose levels and secrete insulin. Insulin has the effect of inhibiting appetite through the central nervous system. Insulin is the only hypoglycemic hormone known at this time and becomes hyperglycemic when there is an abnormality in the insulin gene or in its receptor genes. Insulin promotes the introduction of glucose into cells by increasing the glucose transporter GLUT4 in the cell membrane. Granules containing GLUT4 can be found in the cytoplasm, but insulin quickly expresses its effects by causing them to move toward and adhere to the cell membrane.

Although there are many different hormones that can increase the blood glucose level, only insulin has been found to lower it. The mechanisms for lowering blood glucose levels may have evolved because humans have such a long history of war and famine. However, in times of plenty, it is only insulin that controls elevations in blood glucose levels. In the West and Japan, approximately 20% of the population is said to have diabetes.

As has been explained above, the autonomic nervous and endocrine systems function together during homeostasis. In the autonomic nervous system, the sympathetic and parasympathetic nervous systems compete with each other; in the endocrine system, angiotensin II and ANP or insulin and glucagon also form a system that can be considered to compete. The nervous system regulates hormone secretion, while the endocrine system regulates the activity of the nervous system. As summarized in Chapter 1:2, the biology that we studied in Chapters 1–4 related to the obvious attributes of organisms, such as cell division, genes, and energy metabolism. Research on these attributes has come a long way because of the advent of molecular biology. However, homeostasis of the internal environment is also an important attribute of organisms, and the essence of life seems to lie in the complexity of the mechanisms that regulate it. Thanks to the presence of some guaranteed redundancies, it is also important that organisms can remain oblivious to major changes in the environment surrounding them and that they can retain their balance. The mechanisms underlying homeostasis are biological properties that become endlessly interesting even as we come to know more and more about them.


Appetite Regulation

It is said that the modern era is one of appetite. In developed nations, obesity has been the principle cause of lifestyle diseases, and much more attention has recently been paid to appetite regulation and energy metabolism. Until now, it had been believed that appetite was mainly regulated by the amount of glucose and fatty acids in the blood. However, research targets regarding the effects of hormones have broadened with the realization that insulin inhibits appetite (Refer to this chapter). Lately, an obesity gene has been identified from mice exhibiting overeating and obesity, and abnormalities in this gene or its receptors have been discovered to lead to overeating or obesity. The hormone called leptin, which is the product of this gene, is synthesized in adipocytes and secreted in increased amounts during obesity; it has also been found to suppress appetite. On the other hand, ghrelin, which is mostly synthesized in the stomach, has been discovered to be a hormone that causes secretion of the growth hormone. However, it is also secreted during times of hunger to promote appetite. These hormones act on the arcuate nucleus in the hypothalamus and regulate the activity of the primary neurons that produce neuropeptide Y, which promotes appetite, and proopiomelanocortin (POMC), which is a precursor of the melanin-stimulating hormone that controls appetite (Column Fig. 5-4). These primary neurons regulate hunger by either promoting or suppressing the secondary neurons that produce orexin and melanin-concentrating hormone (MCH), which are appetite-promoting hormones found in the hypothalamus (through its axis) and corticotropin-releasing hormone (CRH) found in the paraventricular nucleus (Column Fig. 5-4). Insulin also acts on the arcuate nucleus to suppress appetite; however, its effects are weak when compared to leptin.

Column Fig. 5-4 Correlation Diagram of the Regulation of Appetite in the Peripheral and Central Nervous Systems

The red “x” mark indicates that leptin or POMC neuron promotion or suppression is weakened. NPY, neuropeptide Y; POMC, proopiomelanocortin; CRH, corticotropin-releasing hormone; MCH, melanin-concentrating hormone; ORX, orexin

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