FIGURE 14 Idealized representation of the effects of epinephrine and growth hormone on plasma concentrations of free fatty acids.
hormones may have some overlapping effects, the actions of the two hormones are usually not identical in all respects. Within the physiologic range of its concentrations in blood, glucagon's action is restricted to the liver. In contrast, epinephrine produces a variety of other responses in many extrahepatic tissues while increasing glycogenolysis in the liver. Variations in the relative input from both hormones allows for a wide spectrum of changes in blood glucose concentrations relative to such other effects of epinephrine as increased heart rate.
Two hormones that produce common effects may differ not only in their range of actions, but also in their time constants (Fig. 14). One may have a rapid onset and short duration of action, whereas another may have a longer duration of action, but a slower onset. For example, epinephrine increases blood concentrations of free fatty acids (FFA) within seconds or minutes, and this effect dissipates as rapidly when epinephrine secretion is stopped. Growth hormone also increases blood concentrations of FFA, but its effects are seen only after a lag period of 2-3 hr and persist for many hours. A hormone like epinephrine may therefore be used to meet short-term needs, and another, like growth hormone, may answer sustained needs.
One of the implications of redundancy for the understanding both of normal physiology and endocrine disease is that partial, or perhaps even complete, failure of one mechanism can be compensated by increased reliance on a redundant mechanism. Thus, functional deficiencies may be evident only in subtle ways and may not show up readily as overt disease. Some deficiencies may become apparent only after appropriate provocation or perturbation of the system. Conversely, strategies for therapeutic interventions designed to increase or decrease the rate of a process must take into account the redundant inputs that regulate that process. Merely accelerating or blocking one regulatory input may not produce the desired effect because independent adjustments in redundant pathways may completely compensate for the intervention.
The net effect of two or more redundant mechanisms acting simultaneously may be equal to, greater than, or less than the sum of their individual effects. Synergy or potentiation are the terms used when the combined effects of two or more hormones are greater than the algebraic sum of their individual effects. An example of this phenomenon is shown in Fig. 15. Both growth hormone and adrenal cortical steroids stimulate the hydrolysis of triglycerides in adipocytes and promote the release of glycerol and fatty acids. Each has a small effect, but together they produce about twice as great an increase in glycerol as would be expected from simply adding their individual effects. Synergy occurs when one of two hormones that act at different sites in a reaction sequence increase a reaction that would otherwise limit the actions of the other agent. For example, if hormone A stimulates cAMP production and hormone B inhibits cAMP degradation, each would somewhat increase the cellular concentration of cyclic AMP, but their combined actions would produce a very large increase. Following the same rationale, when two hormones act through a common step in a reaction sequence, the sum of their individual effects may be greater than their combined effects because some subsequent step in the reaction sequence may become limiting. Such attenuation is less commonly seen than synergy and usually occurs only at very high levels of stimulation or under pathologic conditions.
A special case of synergy that is related to the preceding examples has been called permissive action. A hormone acts permissively when its presence is necessary for, or permits, a biological response to occur, even though the hormone does not initiate or participate in the response. Permissive effects were originally described
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