Bony Targets of Non-"skeletal" Hormones 



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ently because of an increase in the effective size of the pores in the membrane. More- 

 over, later studies (Frazier and Leaf, 1964) indicate that increases in the permeability 

 of the mucosal surface of the bladder epithelial cells to sodium account for the in- 

 creased active transport of 

 his ion which is similarly in- 

 duced. Thus the rate of an 

 active transport system as 

 well as the more obvious 

 passive flow of water across 

 the bladder epithelium can 

 be controlled by changes in 

 membrane permeability. 



Other instances of hor- 

 mone effects on membrane 

 transfer such as the effects 

 of growth hormone on cellu- 

 lar amino-acid uptake (Kno- 

 BiL and HoTCHKiss, 1964) 

 and the apparent stimulation 

 of pinocytosis by insulin 



(Ball and Barnett, 1960) might also be cited as examples. However, in neither case 

 has the ultimate molecular mechanism been as clearly demonstrated. 



0\\& other hormone mediated membrane effect should be mentioned because of its 

 possible importance in bone resorption. This is the effect of certain steroids upon the 

 stability of the lipid membranes which confine the hydrolases of lysosomes. Weiss- 

 man's (in press) intriguing observations of the contrasting effects of neutral steroids 

 depending on their steric form suggest that these agents can become incorporated into 

 lipid membranes and thereby alter their structure in a significant way. 



Turning to the second postulated molecular mode of action of hormones — direct 

 action on an enzyme — a number of examples of apparent hormone effects on 

 enzyme binding of substrates or cofactors including effects of gonadal, adrenal, 

 thyroid and pituitary secretions have recently been cited in a review by a number of 

 authors (Litwack and Kritchevsky, 1964). However, the observations of Tompkins 

 et al. (1963) regarding the effects of certain steroids on glutamic dehydrogenase 

 activity provide a model of another kind of effect whose precision of definition 

 compels me to use it as my example. In these experiments the rate of oxidation of 

 glutamate by crystalline enzyme from liver was followed by the reduction of DPN 

 in the presence of various concentrations of several different estrogenic steroids. As 

 shown in Fig. 4 taken from a recent publication (Tompkins and Yielding, 1964) all 

 inhibited the reaction although to different degrees. Subsequently these workers have 

 shown that this effect is secondary to reversible steroid-induced dissociation of the 

 protein subunits which make up the enzyme. The fact that the dissociated subunits 

 turn out to have increased alanine dehydrogenase activity provides an added embel- 

 lishment to these experiments which so elegantly demonstrate this hormonal effect on 

 an enzyme's structure. 



The third and final molecular target proposed — the transcription of genetic 

 information — has become such a popular site in which to seek the basic action of 



