MECHANISMS OF HORMONE ACTIONS
205
corresponding amines sensitize certain receptors to sympathetic neurohumors.
It was Magnus-Levy (1895) who some 60 years ago demonstrated the
relationship between the basal metabolic rate, of resting level of oxygen
consumption, and the state of thyroid function in man. The determination of oxygen consumption became the most convenient clinical and
experimental measure of thyroid hormone activity. For some time the
prevalent conception of the origin of the multiple effects of thyroxine
was that this hormone increased the energy output of every bodily cell,
and as a consequence heightened all the functional activities of cells,
tissues, and organs. Such a view is not consistent with our accumulated
experience. Thus the respiratory rate of many tissues and cells is not
affected by the thyroid hormone. Most surprising is the behavior of
the central nervous system, which in the hyperthyroid state is undoubtedly "hyperactive," but whose basal oxygen consumption nevertheless remains normal (Barker, 1951). Hypothyroidism, especially in
man, brings with it certain changes in the interstitial tissues, consisting
mainly of an accumulation of fluid rich in proteins (simple and mucoid),
and called collectively myxedema. Myxedematous individuals who are
given drugs capable of raising oxygen consumption (e.g., dinitrophenol)
lose none of the stigmata of myxedema. Neither does dinitrophenol
increase the heart rate or sensitize tissues to minimal sympathomimetic
stimulation, as does crude thyroid or thyroxine. It is therefore evident
that a nonspecific stimulation of cellular respiration is not equivalent to
thyroid action. Additional evidence on this point comes from the specific
developmental effects of the thyroid hormone on tadpole metamorphosis
and its growth-promoting effect in all young animals. It would appear
at the present stage of our knowledge that at least two alternative basic
concepts are possible. The hormone may be changed in the tissues to
several derivatives, one of which serves to stimulate respiration, whereas
another sensitizes to sympathetic neurohumors, and a third increases
protein break-down, etc. In that event, it might follow that tissues such
as brain cannot transform the original "hormone" into the "respirationstimulating" material but can and do produce the "sympathetic sensitizer." Other organs may produce both materials or neither. The second
possible concept would be that the thyroid hormone affects one specific
reaction which controls the rate of cell respiration at a point which
secondarily leads to the other phenomena. Insufficient information is
available to favor either view just now.
Because of the continually broadening knowledge of mechanisms of
cell respiration, primary attention has been and is being directed at the
elucidation of thyroid action on the oxygen consumption of tissues. In
205
corresponding amines sensitize certain receptors to sympathetic neurohumors.
It was Magnus-Levy (1895) who some 60 years ago demonstrated the
relationship between the basal metabolic rate, of resting level of oxygen
consumption, and the state of thyroid function in man. The determination of oxygen consumption became the most convenient clinical and
experimental measure of thyroid hormone activity. For some time the
prevalent conception of the origin of the multiple effects of thyroxine
was that this hormone increased the energy output of every bodily cell,
and as a consequence heightened all the functional activities of cells,
tissues, and organs. Such a view is not consistent with our accumulated
experience. Thus the respiratory rate of many tissues and cells is not
affected by the thyroid hormone. Most surprising is the behavior of
the central nervous system, which in the hyperthyroid state is undoubtedly "hyperactive," but whose basal oxygen consumption nevertheless remains normal (Barker, 1951). Hypothyroidism, especially in
man, brings with it certain changes in the interstitial tissues, consisting
mainly of an accumulation of fluid rich in proteins (simple and mucoid),
and called collectively myxedema. Myxedematous individuals who are
given drugs capable of raising oxygen consumption (e.g., dinitrophenol)
lose none of the stigmata of myxedema. Neither does dinitrophenol
increase the heart rate or sensitize tissues to minimal sympathomimetic
stimulation, as does crude thyroid or thyroxine. It is therefore evident
that a nonspecific stimulation of cellular respiration is not equivalent to
thyroid action. Additional evidence on this point comes from the specific
developmental effects of the thyroid hormone on tadpole metamorphosis
and its growth-promoting effect in all young animals. It would appear
at the present stage of our knowledge that at least two alternative basic
concepts are possible. The hormone may be changed in the tissues to
several derivatives, one of which serves to stimulate respiration, whereas
another sensitizes to sympathetic neurohumors, and a third increases
protein break-down, etc. In that event, it might follow that tissues such
as brain cannot transform the original "hormone" into the "respirationstimulating" material but can and do produce the "sympathetic sensitizer." Other organs may produce both materials or neither. The second
possible concept would be that the thyroid hormone affects one specific
reaction which controls the rate of cell respiration at a point which
secondarily leads to the other phenomena. Insufficient information is
available to favor either view just now.
Because of the continually broadening knowledge of mechanisms of
cell respiration, primary attention has been and is being directed at the
elucidation of thyroid action on the oxygen consumption of tissues. In