Intracellular Receptors: New Instruments for a Symphony of Signals In
the late eighteenth century, it was proposed on theoretical grounds that
each of the body's organs, beginning with the brain, must be "a factory
and laboratory of a specific humor which it returns to the blood", and
that these circulating signals "are indispensable for the life of the
whole" (Bordeu 1775). During the nineteenth cen- tury, some remarkable
physiological experiments revealed the actions of humoral factors that
affected the for and function of multiple tissues, organs and organ sys-
tems within the body (Berthold 1849); much later, the chemical and
molecular na- ture of some of those factors was determined. Against this
deep historical backdrop of the founding studies of intercellular
signaling, molecular biology sprang into existence a mere forty years
ago, rooted in the revelation of regulable gene expression in bacteria.
But contemporaneous with those classical analyses of transcriptional
regulation of the lactose operon, the mod- em era of signal transduction
was inaugurated by the identification of cAMP as a second messenger ---
an intracellular mediator of hormonal activation of glycogen catabolism
(Sutherland and RaIl 1960). Later in that same decade, it emerged that
cAMP is a critical signal not only in metazoans, but even in bacteria,
where it serves an analogous function as a critical switch that
activates expression of genes re- quired for catabolism of complex
carbon sources, including those of the lactose operon.