Hormones in Context: Systems and Controls

 
Nearly all introductory accounts use the example of a room thermostat that controls central heating. As heat is lost from the room, it cools down, and the thermostat switches the heating on. Once the room reaches the required temperature (known to engineers as the set point) the heating switches off.

This a simple example of what is known as negative feedback. The temperature of the room is low because of heat loss, so heat is put into the system to correct the error. In other words there are two opposing effects - the heat out of the system and heat in.

I want to carry this example a little further. In practice, it takes time for the boiler to heat the room. It would be possible to have a powerful boiler, which would be useful, perhaps, when warming the room from cold, but the temperature would tend to overshoot. The rate of heating needs to be about the same as the rate of cooling down. Also there are delays, due to the rate of heat input or loss, relative to the sensitivity of the switch. Switching is a little late in each direction and the room varies very slightly in temperature. It overshoots in each direction by a small amount. There are very expensive and complex systems that correct for the magnitude of the error, the length of time that it has existed, and the rate of the change in the error. However we don't need to discuss them here.

This simple case can be described in the form of a graph. The system could be arranged so that the heat rises, when first switched on, so that it rises steadily towards the set point, though it might take forever and a day to reach it (Figure 1)

An engineer would say the system is 'over-damped.' Alternatively, one could use a very sensitive system. The result might be that it overshoots wildly, then for a long time swings back and forth around the set-point, called 'ringing.' (Figure 2)

The ideal is reckoned to be what is known as 'critical damping', with just one overshoot (Figure 3). This is true of any simple system of this sort. For example, a crude test of the dampers on a car is to press down on the bonnet. On releasing it, the front of the car should rise and fall once, then settle.

In practice, even central heating systems are more complex than this. On a cold day someone might turn up the thermostat and raise the set point. Or there may be a time switch, so that the heating is only switched in the mornings and evenings.

One might visualise an industrial oven, where the process requires a gradual rise and fall in temperature, which could be handled by a separate controller changing the set point. Thus we have two nested systems.

In passing, there is another term which is sometimes used: feed forward. If you expect the following morning to be cold, you can use a time switch to warm the room before you get up.

As another example, on a hot day, dehydration causes body fluids to be lost through sweating. This is sensed by the hypothalamus, and there is motivation to replace the fluid by drinking. However, by the time the fluid is absorbed, one might be dehydrated. So, one tends to feel thirsty in response to the high temperature, rather than the body's fluid balance, well before the latter becomes dangerously disturbed.

The central feature of a negative feedback system is that, if it is working properly, it is fundamentally stable. To recap - any error producing a change away from the set point is countered by an input in opposition to the error, which restores the equilibrium.

Suppose, however, the input is in the same direction as the error, in other words, it adds to it. This is positive feedback. To return to the analogy of the motor car - the driver controls it with the throttle, in effect a negative feedback system. When one comes to a hill one opens the throttle to overcome the increased gravity. Going downhill, gravity is pulling forward, so one closes the throttle.

Imagine the effect of opening the throttle when going downhill. In other words the input is in the same direction as the error.

Your vehicle will go faster and faster. Assuming the hill is long enough, only one of three outcomes are possible. Either the vehicle speed rises to a 'saturation' level where wind resistance and other forces limit any further rise. Or destruction occurs as the engine fails. The only other possibility is to put the brakes on.

So, whereas, negative feedback is a self-balancing system, positive feedback is intrinsically unstable. There are occasions when positive feedback is used deliberately in control systems, and it occurs quite commonly in the body. It gives a very rapid rise in output, a very quick response. However, whenever one comes across such a system, one should look for the way in which it is terminated.

The problem of studying natural processes is that, unlike the traditional sciences of physics and chemistry, we are considering a myriad of interlocking, interacting, nested systems. The cell is maintained at a steady 37 degrees Celsius with an aqueous, slightly alkaline environment. This allows complex reactions at the ionic level, with complex organic molecules being synthesised and being broken down.

Within a multicelled organism, individual cells live and develop within an environment, while the organism is both acted on and reacts with the external environment.

The fundamental feature of a 'system' is that it is said to be 'closed' by 'feedback'. Strictly, we should in this case speak of a 'closed loop'.

Consider a motor car, which does not have speed regulation as part of its mechanism. When standing by the roadside, it is simply an, admittedly elegant, contrivance of metal and plastic. One could consider it as only 'being' a motor car when it is performing its function of transporting its driver, who is, nominally at least, controlling it. Thus, in this case, the driver provides the feedback loop.

In fact, real-world processes from the genetic level upwards are so complex that many of the control variables are unknown, and for an individual organism possibly unknowable.

Science begins by reducing the problem to a manageable size; by visualising the activity of one particular system. In other words, a system which is 'closed' to any external forces. The problem is that science then tends to consider that that is all there is to it.

The central criticism of a 'reductionist' account, such as this, of a single simple system in isolation, which may well be 'closed loop' in itself, is that, in 'real life' it is 'open' to an environment. Any one system exists in the presence of many others.

Thus in economics, rising prices cause demand to fall, which causes prices to fall again. That is the theory - a closed negative feedback loop. In practice, people may insist on higher salaries, to be able to afford the product - food, for instance. Prices then increase because people can afford them, whereupon, people ask for even more money - a positive feedback loop.

Hormones in action.

The process of utilising food is digestion. The main nutritional elements entering the blood stream are sugars, amino acids and fats. Anyone who has done a basic biology course will know that the body gains its energy mainly from circulating sugars in the bloodstream, by breaking them down into carbon dioxide and water.

It does this by means of enzymes, chemicals that facilitate reactions between other chemicals while remaining unchanged themselves. It is a description that belies their sheer complexity. They are fundamental to the metabolism of living organisms. There are hundreds of different enzymes, all specific to certain processes, often causing reactions to occur in chemicals so stable that the reaction might never otherwise occur.

A idea of the sheer complexity of the body's chemical processes will be gained when one realises that the sugar, in the form of glucose, goes through no less than twenty stages, each utilising separate enzyme reactions, to produce carbon dioxide and water, as energy is released. Each stage is precisely controlled according to the needs of the moment to produce exactly enough, but not too much.

Surplus glucose is converted into either glycogen or fat, for storage, and converted back when there is an increased energy requirement. The names of the principal hormones involved are familiar to most people - Insulin and Adrenalin. Insulin, synthesised by the pancreas, is involved with diabetes, which is an error of sugar metabolism, where an individual's blood sugar is too high or low. Although there are various complex processes in various cells and local sites for regulating glucose levels, insulin controls the general body level as part of the process of storing it as glycogen.

Adrenalin is familiar that it has passed into every day language, when we speak of an "adrenalin surge." It is produced by the adrenal gland and promotes the conversion of stored glycogen to glucose.

Two other hormones, glucagon and thyroxine are also involved in converting stored fat back into blood sugars, however adrenalin is considered the main process. While the others, especially insulin are relatively slow in their action, adrenalin is fast acting, promoting the conversion of glycogen to glucose in a series of stages, each of which is controlled, but which act in cascade. Therefore only a small amount of adrenalin is needed to produce a large output of glucose. It is released by the adrenals in a series of short pulses, and is quickly broken down by the body.

One way of looking at it is that insulin and adrenalin/glucagon act in opposition to each other to produce a balanced blood sugar system.⁽¹⁾ Another is that there are two feedback control systems, insulin controlling the long term overall balance, while adrenalin is a fast-acting, extremely sensitive system, as is required to deal with events which require immediate attention. The adrenalin system is superimposed on the insulin system, and, in general reacts more quickly, though insulin production also appears to be inhibited,

What happens when we meet a potentially threatening situation? Because, in evolutionary terms, we make the choice of fighting or running, the bodily process that occurs is as already mentioned the "fight or flight" reaction.

However, many writers point out that what is important is the moment when threat is perceived, the so-called "Startlement reflex" The first reaction is to freeze, there is a sharp intake of breath and the muscles tense. While the intake of breath is held, a proportion of the blood flow is diverted to the muscles and the brain.

Muscles are supplied with blood ready for action, while the brain gets a charge of oxygen while it thinks a great deal about the threat. In addition extra glucose is released into the bloodstream

Two systems come into operation,. The first involves adrenalin and noradrenalin, which causes the heart rate to increase and the blood vessels of the gut to contract. In this case, it is acting as a neurotransmitter, since it is acting on the nervous system. Thus there is an immediate increase in blood flow to the muscles and the brain. Adrenalin and noradrenalin are released into the blood stream, changing the blood sugar balance, and also acting on various receptors around the body, particularly the muscles, which accounts for the physical feelings at moments of fear. Also there is an increase in a group of hormones, called corticosteroids, which take part in the process of releasing energy-producing substances from reserves.

The effect is to cause the heart to beat faster, more blood flows to the muscles instead of to the internal organs, such as the digestive system. If the animal is able to fight, or to flee, the resulting activity makes use of these changes, and as activity ceases, the body's balance returns to normal.

The point that some stress counsellors make is that threat situations arise for humans in many situations, from a much wider range of emotions than simple physical threat. In addition, we are socialised not to act in response. If your boss makes a derogatory remark about you, you can't easily respond, if you want to keep your job. As a result the bodily threat responses are not dissipated. Blood flow is to the muscles, resulting in tension, away from the viscera, resulting in poor digestion. Heart rate remains high, and the sugar balance in the blood is inappropriate.

Under conditions of unresolved stress, adrenalin, noradrenalin, cortisone, thyroid hormone and growth hormone become elevated, while insulin, testosterone, estradiol, and estrone decrease. In addition, endogenous opiates, endorphins, produced as a defence against pain, may remain in the circulation, producing lethargy.

The purpose of this diversion is to give a flavour of the dynamism of the body. You may be strolling in the park, you might buy an ice cream. It's time to go, and you see a bus on the way, so you break into a run. When you get home you may sit for a while reading or watching television. Then later, you have a larger meal. Here is a system that is continually adjusting to the moment by moment needs, yet it is no more than a simplified picture. Other systems are at work attending to other needs, and all interacting with each other.

The detailed description given so far may seem less than relevant in a book about gender, but it illustrates the sensitivity and complexity of the body's chemistry. It also gives a conceptual background to a discussion of the so-called sex hormones.

1. Rose, S., (1991) The Chemistry of Life, London: Penguin Books.

NEXT Estrogens and Androgens.