452 



PHYSIOLOGY OF GONADS 





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I--|(..7.1. Munlry l,yi„,pliy>r,-ini,iiz<Ml 1 y,-uv | hvm, ,u^ly . I'., Hide- :nv ,n ) ,i n^i .—in . ' ~::,-i>s 

 (jl (le\f'lu]iiiieiil. C<nic('iitr;itiun ul' uorylcs m ihc corlcx n'S('inl)lfs llial in iVlal or jusciiilc 

 o\aiie8. No evidence of estrogen production in this animal. (Courtesy of Dr. Ernest Knobil.) 



foiii' layers of granulosa cells (Mandl and 

 Zuokerman, 1952a). The increase in size of 

 the growing follicle is relatively constant 

 until the stage of antrum formation (Paesi, 

 1949a ». Follicles grow and develop to this 

 stage in rats and guinea pigs even after 

 hypophysectomy (Dempsey, 1937; Paesi, 

 1949b). It is thus apparent that the gonado- 

 trophic hormones of the pituitary are not 

 essential for the early growth of ovarian 

 follicles (Fig. 7.1). The rate of this early 

 follicular growth may, however, be acceler- 

 ated in the presence of certain, but perhaps 

 not all, gonadotrophic hormones (Pencharz, 

 1940; Sim])son, Evans, Fraenkel-Conrat and 

 Li, 1941 ; Gaarenstroom and de Jongh, 1946; 

 Payne and Hellbaum, 1955). 



As the granulosa of the growing follicle 

 ])roliferates, the surrounding tissue differ- 

 entiates into theca interna. Dubreuil (1942, 

 1948, 1950) postulated that the granu- 

 losa j)roduces an inductor substance which 

 causes the differentiation of the theca in- 

 terna. Hisaw (1947), in a review of the 

 literature bearing on this point, also sug- 

 gested that there must be organizers within 



the developing gramdosa cells which stimu- 

 late tlifferentiation of the theca interna. 

 Furthermore, this autonomous process con- 

 tinues until the follicle reaches a stage of 

 development at which it becomes responsive 

 to gonadotrophic hormones. Hisaw called 

 this the stage of "comjietency." 



Somewhere in this process estrogens seem 

 to have a role, or, if the ojjinions expressed 

 by Bullough (1943) and the other investi- 

 gators whose work has just been cited can 

 be confirmed, perhaps there is a continued 

 stimulation by these substances. If large 

 doses of estrogen are administered to im- 

 nuitui'c or to liypopliyscctomi/ed immature 

 rats, many follicles (k'\x'lop to the early 

 antrum stage within 72 hours. The theca 

 interna differentiates ai'ound these estrogen- 

 stimulated follicles. When immature rats 

 ai'e giv(m large doses of estrogen there is 

 a <le(iiiil(' incicasc in ox'arian weight and 

 in the iiuiiihei' of medium-sized follicles 

 ( ]''ig. 7.2 1 ; small amounts, on the othei' 

 hand, ai'e iiihihitoiy (Paesi, 1952). In- 

 creased giowth of large follicles, or at least 

 a retai'dation of their degeneration, has 



