Principles of metabolic regulation
7.2 Hormones
Control of the release of energy from carbohy- drate and lipid stores during exercise, as well as the synthesis of glycogen and TAGs following meals and the resynthesis of muscle protein, are regulated in part by hormones. From the context of energy production and energy storage, we need to be aware of the role of the following hormones – catecholamines (adrenaline and
noradrenaline), insulin, glucagon, growth hor- mone (GH), and cortisol. However, as muscle protein synthesis is important to maintain or increase muscle mass, this demands that an appre- ciation of the roles of insulin andtestosterone is required.
Table 7.1 highlights the key processes regulated by these hormones and also their target tissue.
From an energy production and storage perspec- tive, the key tissues include muscle, liver and adipose tissue, while muscle remains the tissue for maintaining protein synthesis.
During exercise there is an increase in circu- lating catecholamines, glucagon, GH and cortisol, whereas insulin levels decrease (Figure 7.1A). As a consequence, there is an increase inglycogenol- ysis and glycolysis in muscle and liver, an increase inlipolysis in muscle and adipose tissue, an increase (after 20–30 minutes or more) in gluconeogenesis in the liver and an increase in protein degradationin liver and muscle. The net effect is that circulating concentrations of glucose remain fairly constant (at least for 60–90 minutes or so), whereas fatty acids, glycerol and ketones increase and amino acids increase. These are the energy sources that can be utilized by muscle.
If a carbohydrate drink, such as a sports drink, is ingested during the exercise bout, a slightly different scenario is presented (El-Sayed et al., 1997). Under this circumstance, the levels of insulin increase while there are lower levels of the other hormones. The effect is reduced lipolysis, gluconeogenesis and protein degradation, whereas glycolysis is enhanced. There is thus a benefit to drink carbohydrate drinks during exercise from a protein breakdown perspective, but not from a
‘fat burning’ perspective.
In addition to the effects of the hormones on energy availability during exercise, it is impor- tant to appreciate that hormones also regulate the recovery process after exercise. This includes not only resynthesis of muscle glycogen stores ready for the next training session, but also promotion of protein synthesis in muscle – so muscle struc- ture can recover. Additionally, when meals are consumed after training, the products of digestion and absorption have to be incorporated into body
Table 7.1 Hormones, the major tissue secreted from, their target tissue, and their effect on various biochemical processes
Hormone Target tissue Processes influenced
Insulin Muscle ↑glycogenesis;↓lipolysis;↑protein synthesis (β-cells of pancreas) Adipose tissue ↑lipogenesis;↓lipolysis
Liver ↑glycogenesis
Glucagon Muscle ↑glycogenolysis;↑ protein degradation
(α-cells of pancreas) Adipose tissue
Liver ↑glycogenolysis;↑ gluconeogenesis;↑protein degradation
Adrenaline Muscle ↑glycogenolysis;↑ lipolysis
(adrenal medulla) Adipose tissue ↑lipolysis
Liver ↑glycogenolysis
Noradrenaline Muscle ↑glycogenolysis;↑ lipolysis (adrenal medulla) Adipose tissue ↑lipolysis
Liver ↑glycogenolysis
Growth Hormone Muscle ↑protein synthesis;↑lipolysis (hypothalamus) Adipose tissue ↑lipolysis
Liver ↑gluconeogenesis
Cortisol Muscle ↑protein degradation
(adrenal cortex) Adipose tissue ↑lipolysis
Liver ↑gluconeogenesis
Testosterone Muscle ↑protein synthesis
(testes) Adipose tissue ↑lipolysis
Liver
Oestrogen Muscle
(ovaries) Adipose tissue ↑lipolysis
Liver
Progesterone Muscle ↑glycogenesis
(ovaries) Adipose tissue ↑lipolysis
Liver ↑gluconeogenesis
tissue, such as the storage of carbohydrate and lipids, and of course protein in muscle.
Once again, hormones help to regulate these post-prandial (after a meal) events.
What we now need to explore is how the hor- mones affect their target tissue in order to mobilize energy substrates as illustrated in Figure 7.1A, aid recovery and promote storage.
The hormonal regulation of cells invariably concerns either the activation of inactive enzymes (as produced by peptide hormones and cate- cholamines) or the formation of new enzymes
(de novo synthesis) from protein synthesis (as for steroid hormones). Most of the enzymes involved in the energy-producing and energy- storage processes exist in two forms, i.e. an active form and an inactive form. The active form is required to ‘drive’ the process.
For example, glycogenphosphorylaseneeds to be in its active form to promote breakdown of glycogen during exercise, and so would PFK for glycolysis or ATGL and HSL for lipolysis. Dur- ing rest periods, these enzymes would be present in the cells in their inactive form.
−3002060100120 Plasma Adrenaline (nmol/I)
3 2.5 2 1.5 1 0.5 0 −3002060100120 Time (min) (a)
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−300204060 Time (min)Time (min)Time (min) Plasma Insulin (mU/I)
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Glucose Saline
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650 Figure7.1Changesincirculatingconcentrationsofhormones(a)andmetabolites(b)duringcyclingexerciseat70%VO2maxfortwohourswithand withoutglucoseinfusion(adaptedfromMacLarenetal.,1999)
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Plasma Lactate (mmol/l)
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Plasma Glycerol (µmol/l)
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(b) Figure 7.1 (continued)
Hormones have the capacity to affect the activ- ity of these enzymes, and so can ‘turn on’ a cell.
From a hormone action perspective, there are two ways by which hormones influence their target cells:
• Peptide hormones (in effect polypeptides) and the catecholamines are lipophobic and so are unable to pass through the plasma membrane due to the internal domain of the membrane con- sisting of fatty acid chains. Consequently, they affect their target cells by attaching to receptors on the surface of the cell membrane and thereby influencing the cell. Peptide hormones include insulin, glucagon, and growth hormone (GH).
• Steroid hormones arelipophilicand are thereby capable of passing through the target cell
membrane and attaching to a receptor molecule in the cytoplasm, from which protein synthe- sis is stimulated. Examples include cortisol, testosterone, oestrogen, and progesterone.