MAMMALIAN OVARY 



453 



y^ 



Fig 7.2. Intact immature lat given estrogen for 3 days. Active proliferation of granulosa 

 in many follicles. Decreased incidence of atresia and hypertrophy of theca. (Courtesy of Dr. 

 J. T. Bradburv.) 



Ijeen reported in hypuphyscctoiuizcd I'uts 

 given stilbc-^trol (Pencharz, 1940; Williams, 

 1944; Desclin, 1949; Payne and Hellbaum, 

 1955; Ingram, 1959 1. Histologically, when 

 estrogen is given, there is a marked increase 

 in mitotic activity of the granulosa cells and 

 a decrease in atresia (Williams, 1945a; de 

 Wit, 1953; Payne and Hellbaum, 1955; 

 Payne, Hellbaum and Owens, 1956; Wil- 

 liams, 1956). The fact that estrogen stimu- 

 lates the follicle and protects it against atre- 

 sia suggests that the granulosa is not a 

 significant source of estrogen. On the other 

 hand, if estrogen is jiroduced by the theca 

 interna, it could exert a localized stimula- 

 tory action on the membrana granulosa 

 (Corner, 1938; Bullough, 1942b, c, 1943). 

 The differentiation and development of the 

 theca interna is nicely timed for a localized 

 jiroduction of estrogen around each Graafian 

 follicle. 



Estrogen not only stimulates the granu- 

 losa to proliferate, but also renders the 

 follicles more responsive to exogenous go- 

 nadotrophins. Williams (1945b) found that 

 the ovary in the stilbestrol-treated hypo- 

 l^hysectomized rat was more responsive to 

 small doses of pregnant mare serum 

 (PMS) than was the ovarv in the intact 



immatui'e rat. Payne and Runser (1958) 

 found that stilbestrol augmented the re- 

 sponse of hypophysectomized immature rat 

 ovaries to exogenous pituitary extracts. In 

 Bradbury's experience at Iowa 48 hours of 

 stilbestrol pretreatment rendered the ovaries 

 of both intact immature and hypophysec- 

 tomized rats more responsive to Armour's 

 LH (Lot No. R377242H), but not to Ar- 

 mour's follicle-stimulating hormone (FSH) 

 {Ah 1027) . Furthermore, increasing the dos- 

 age of stilbestrol from 0.02 mg. to 0.2 mg. 

 markedly increased the response of the 

 ovaries to a given dose of LH. He suggested 

 that the possibility should be exi)lored that 

 the local (})erifollicular) concentration of 

 estrogen determines the resjionsiveness of 

 the maturing follicles. Thoughtful discus- 

 sions of the subject are given by Paesi 

 (1952) and by Bradbury (1961). The for- 

 mer suggested that 2 or 3 types of estrogen 

 action may be involved in the stimulation 

 of the ovary which is seen wdien estrogen is 

 administered. Bradbury applied estradiol 

 or stilbestrol to one ovary of the immature 

 rat, leaving the other ovary untreated. The 

 various unilateral responses — increase in 

 weight, formation of corpora lutea, greater ■ 

 reactivity to gonadotrophins — demonstrated 



