CI.AKA M. SZKC.O 



15.3 



(iross alterations in structure and function of the tarj^et cell would result from 

 enhanced and directed metabolism. 



The extension of this mechanism with certain moditications to hormones other 

 than selected steroids can also be demonstrated. Only a few of the more striking 

 examples of the latter will be mentioned. 



It is scarcely necessary to emphasize the provisional nature of these proposi- 

 tions. This undoubtedly premature attempt to extend physicochemical princi- 

 ples to the overwhelmingly complex target cell entails an inordinate number of 

 assumj)tions.. 



INFLUENCE OF STEROIDS ON UTERINE WEIGHT AND WATER CONTENT 



In attempts to dissect the primary effect from the surrounding shell of non- 

 specific consequences of estrogen action upon the uterus, reliance must be 

 placed upon the time-course of the metabolic events which follow hormonal 

 stimulation. Thus, while the cumulative effects of the changes which occur in 

 response to estrogen are hypertrophy and hyperplasia, it is generally recognized 

 that true growth of this organ is preceded by, and, in fact, predicated upon, 

 earlier moditications of cellular composition and enzymatic activity. 



The early period is characterized by an acute shift in water and electrolyte 

 distribution, associated with enhancement in blood supply. Profound changes in 

 energy metabolism and respiratory activity may also be detected. The second, 

 or true growth phase is distinguished by the generally accepted evidences of 

 increase in protoplasmic substance: increment in dry weight, deposition of 

 organic and nitrogenous constituents, and full-blown morphological signs of 

 cellular proliferative activity. 



Figure i depicts the time-course of water imbibition by the uterus of the adult 

 ovariectomized rat after a single intravenous dose of 0.5 microgram of estradiol- 

 17 /3 in saline (23) per 100 grams body weight. 



It will be noted that a striking augmentation in the water content of the 

 uterus occurred within 46 hours; a secondary peak may have taken place at 20 

 hours. The total uterine weights at these two periods were quite similar, but the 

 4-hour increase was attributable almost entirely to water imbibition, whereas 

 the 20-hour increase was associated with significantly elevated uterine solids and 

 histological evidences of cellular proliferation. Accordingly, these tw^o time- 

 intervals of duration of hormonal stimulation, as likely to be representative of 

 the primary and secondary phases of the response complex, were chosen for most 

 of the studies reported herein. 



The results shown in figure i are quite similar to those noted by Astwood (i) 

 after the subcutaneous administration of estradiol or estrone to the immature 

 rat. This investigator and co-workers first directed attention to the biphasic 

 character of the uterine growth response to endogenous or exogenous estrogenic 

 stimulation, and also observed that the rapid early change in intra- and extra- 



