MECHANISMS OF HORMONE ACTIONS
209
system which oxidizes isocitrate in the presence of DPN (diphosphopyridine nucleotide). Estriol, progesterone, stilbestrol, and testosterone
were only one-thousandth as active. It is far too premature to speculate
on the possible relationship such an action may bear to the total estrus
phenomenon in vivo.
VI. GENERAL CONSIDERATIONS
Our present meager store of information concerning mechanisms of
hormonal action does not, of course, allow us to make broad generalizations. This field of investigation finds itself in the same position as do
the other areas of biological research, which attempt to deal with the
links between the chemical reactions which provide energy and the
functional apparatus which directs its use. The enormous labors of the
enzyme chemist during the last thirty years created the feeling among
many biologists that here was the key to all cell and organ physiology.
Many problems were indeed solved by this approach, but with few exceptions these dealt with the energetics, the "power supply" of the cell,
and not with the utilization of the "power" for regulation of activity.
The concept that a drug or a hormone could "act" only by being or becoming a part of an enzyme system or a specific inhibitor thereof, proved
too confining a view and not as productive as was hoped. The conviction
of the biologist that form and function are interdependent is pervading
present-day biochemistry. Cytoarchitectural considerations are leading
to the creation of a geometrical outlook in cell chemistry, in addition to
the purely arithmetical concepts of concentration, rate, equilibrium, etc.
It is the aim of this review to draw attention again to the views held
by the older generation of general pharmacologists (Loewi, 1952; Clark
1933) that the site of action of most "drugs" is the cell surface or
boundary region. This is the area of contact with the world external to
the cell. It serves at once many functions. Notably, it is the region of
the cell which is a combined general sense organ, and it also fulfills the
same purposes for the cell as does the gastrointestinal tract for the
animal as a whole—digestion, absorption, and excretion. Rothstein
(1954) has recently reviewed in detail the complex enzymology of the
cell surface, and the reader is referred to his monograph for the detailed
references.
In the course of evolutionary development a complex communication
system develops. The final messenger seems always to be a specific
chemical material, brought to the effector cell either via nerve impulse
or via the blood stream. It is known that in certain specialized cell
systems, such as the neurones and muscle fibers, messages are received at
the cell surface and are then transmitted for action into the cell interior.
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