Primary Mechanisms of Hormonal Action on 



Target Cells'^ 



CLARA M. SZEGO 



Department of Zoology, University of California, Los Angeles, California 



IT SEEMS SCARCELY NECESSARY to point out to this Sophisticated group that 

 participation of the endocrinologist in the present symposium is fitting and 

 proper. The time is long past for the view, based largely on the early descriptive 

 phase of the metamorphosis of this field, that endocrine regulation is character- 

 ized by relatively gross and imprecise responses which defy quantitative 

 evaluation. 



Administration of a hormone to an appropriate test object gives impetus to a 

 series of biochemical events which may culminate in functional and morphologi- 

 cal changes in the target tissues. In the present discussion, attention will be 

 directed primarily to the action of certain steroid hormones upon a typical 

 target organ, the uterus, and emphasis will be placed upon analysis of a) the 

 metabolic pathways upon which the hormone exerts its primary or 'triggering' 

 influence; b) the relationship between this primary effect and the succeeding, 

 relatively nonspecific, consequences of hormonal stimulation; and c) the mode 

 of interaction between the hormone and the receptor which, in effect, together 

 constitute the 'trigger.' 



Such an analysis requires gross oversimplification because of our lack of pre- 

 cise knowledge in these areas. It would appear, however, that the time is ripe 

 for advancing a working hypothesis of the nature of hormone action (cf. 24, 36) 

 which lends itself to experimental testing. In essence, this may be stated as fol- 

 lows/or the special set of circumstances indicated above. The 'trigger' of hormone 

 action may be considered to be the resultant new biochemical entity formed by 

 the interaction of the hormone and an active receptor site, most likely protein, 

 of the target cell. The primary reaction 'triggered' by the presence of this 

 complex would appear to be the enhanced rate of penetration into the cell of one 

 or more key metabolites. The nonspecific biochemical responses secondary to 

 this fundamental transfer reaction may simply be a function of the increased 

 availability of the critical substance to the enzymatic machinery of the cell. 



' Supported by a research grant from the National Cancer Institute, National Institutes 

 of Health (C-1488), and by Cancer Research Funds of the I'niversity of California. 



- Several asjiects of this toiMc have l)een discussed in |)revious reviews with the collabora- 

 tion of Dr. Sidney Roberts, Department of Physiological Chemistry, School of Medicine, 

 University of California Medical Center, T.os Angeles (cf. 24, 26, 36). 



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