47() 



PHYSIOLOGY OF GONADS 



different, but they are ai)parently eriually 

 specific (Daughaclay, 1959; Slaunwhite and 

 Sandberg, 1959). A considerable specificity 

 of the binding sites may be involved ( Sand- 

 berg, Slaunwhite and Antoniades, 19571. 

 Daughaday (1959) states that separate 

 binding sites may exist for each of the 

 steroid hormones studied, and Szego (1957) 

 suggested that a competition for these sites 

 may be the basis for antagonisms which are 

 known to exist in many steroid interactions 

 (Courrier, 1950; Hisaw and Velardo, 1951; 

 Roberts and Szego, 1953; Velardo, 1959; 

 Velardo and Hisaw, 1951 ; Zarrow and 

 Neher, 1953). 



The most important consideration has 

 to do with the significance of protein bind- 

 ing for the steroid hormones, and, in the 

 present chapter, the significance for estro- 

 gen and progesterone. Roberts and Szego 

 (1946, 1947) and Szego (1957) proposed 

 that formation of the estrogen-protein com- 

 plex is necessary for the transport and 

 activity of endogenous and exogenous estro- 

 gens. Riegel and Mueller (1954), on the 

 other hand, found that the protein-estrogen 

 complex they used had only a slight, if any, 

 estrogenic activity, and Daughaday (1958, 

 1959) expressed the opinion that the un- 

 bound steroid hormones of the plasma are 

 probably the biologically significant moie- 

 ties. He suggested that the degree of pro- 

 tein binding imposes a major restraint on 

 the passage of hydrocortisone (and pre- 

 sumably other steroids) through the cajiil- 

 lary membranes, but pointed out that this 

 view has not yet been established. He then 

 asked, in the event that the steroid-protein 

 complex does not function in the transi)ort 

 of hormones from the vascular component 

 to the cell, is it likely that the presence of 

 a steroid-protein complex stabilizes the 

 pliysiologically significant concentration of 

 unbound steroid very much as buffer salts 

 stabilize the small concentration of hydro- 

 gen ion? In this way, he continued, the 

 organism would l)c protected against the 

 rapid changes in concentration which char- 

 acterize an unbuffered system. 



At tiic ]ir(>sent stage in this controversial 

 sul).iect, any hypothesis with res])ect to the 

 significance of the protein binding of steroid 

 hormones must be tentative. It would seem, 

 however, that whatever emerges will have 



validity only if it is compatible with the 

 cyclic waxing and waning of reproductive 

 phenomena. If the unbound, rather than the 

 bound fractions, are the active fractions, the 

 functioning of the ovarian steroid hormones 

 must dei)end on the presence of unbound 

 fractions, in some way made available at 

 cyclic intervals to the tissues on which these 

 hormones act. It would seem, too, that the 

 significance of the increased capacity for 

 l)inding in i)rcgnancy (Rakoff, Paschkis and 

 Cantarow, 1943; Baylis, Browne, Round 

 and Steinbeck, 1955; Daughaday, 1959; 

 Slaunwhite and Sandberg, 1959) should be 

 a ])art of the picture. Tentatively, this 

 greater binding capacity on the part of 

 the ])regnant adult, coupled with an ina- 

 bility of the developing fetuses to bind 

 androgens, might account for the failure of 

 the adult to be affected by the presence of 

 androgen at a time when the genital tracts 

 and neural tissues of the female fetuses she 

 is carrying are undergoing profound modi- 

 fications (Phoenix, Goy, Gerall and Young, 

 1959; Diamond, 1960). 



VI. Age of the Animal and Ovarian 

 Functioninij 



The position of the ovary is such — at one 

 and the same time being dependent on the 

 pituitary, possessing its own varying ca- 

 pacity to function, and having an effective- 

 ness which is limited by the responsiveness 

 of the tissues on which its hormones act — 

 that no simple consideration of the relation- 

 shii) between the age of the animal and 

 ovarian functioning can be given. An in- 

 vestigation, therefore, should be planned 

 accordingly and we find experiments in 

 which the amount of gonadotrophic stimu- 

 lation was varied when age was constant, 

 and experiments in which age was the varia- 

 ble and the amount of gonadotrophin the 

 constant. If hypo- or hyper-responsiveness 

 of the tissues is suspected, the point can be 

 checked by the use of spayed animals given 

 variable amounts of ()\-arian hormones. 

 When information of these sorts is brought 

 together, a fairly accurate account of the 

 relationship between age of the animal and 

 ovarian activity can l)e ])repared. 



The results fi'oni many studies have re- 

 vealed that the ovaries in both inunature 

 and senescent females are potentially able 



