MAMMALIAN OVARY 



467 



1951) and by the high titer of estrogens in 

 the urine from ovariectomized rats on a high 

 fat diet (Ferret, 1950). 



Corner, as long ago as 1938, in a consider- 

 ation of the subject, emphasized that there 

 is only circumstantial evidence that the 

 ovary is the major site of estrogen produc- 

 tion. Attempts to extract estradiol or any 

 other estrogen from ovarian tissue had 

 yielded very small amounts. MacCorquo- 

 dale, Thayer and Doisy (1936) processed 4 

 tons of hog ovaries and recovered about 6 

 mg. estradiol from each ton. They estimated 

 that the concentration in liquor folliculi was 

 of the order of 1 part in 15,000,000 and that 

 about 0.1 of this concentration is in the rest 

 of the ovarian tissue. There are much better 

 sources from which "ovarian hormone" can 

 be extracted than from the ovary, i.e., pla- 

 centas, pregnancy urine, the urine of the 

 stallion or boar. The adrenal is also a source 

 and there may be other tissues as well, for 

 Bulbrook and Greenwood (1957) reported 

 that urinary estrogen continued to be ex- 

 creted after oophorectomy and adrenalec- 

 tomy of a breast-cancer patient. 



Whatever the relationships are quantita- 

 tively between the follicles and the other 

 estrogen-secreting tissues, the evidence that 

 the follicles are a major source of estrogenic 

 substances remains impressive. This is also 

 true of the corpus luteum. The human cor- 

 pus luteum produces as much, or more, es- 

 trogen than was produced during the follicu- 

 lar phase. In the rat and mouse, estrogen 

 production during the luteal phase must be 

 low because more than 1 part of estrogen 

 nullifies the action of 1000 parts of proges- 

 terone in these species ( Velardo and Hisaw, 

 1951). By contrast, ratios as high as 100 

 parts of estrogen to 1000 parts of progester- 

 one enhance the progestational reactions in 

 women (Long and Bradbury, 1951). 



The different tissues of the ovary — mem- 

 brana granulosa, theca interna, and inter- 

 stitial cells — have been studied in efforts to 

 ascertain whether they are sites of the pro- 

 duction of specific hormones. Inasmuch as 

 unruptured follicles and corpora lutea se- 

 crete both hormones, the two structures 

 must be considered. It has long been known 

 that corpora lutea secrete estrogen as well 

 as progesterone. Evidence supporting the 

 conclusion that jirogesterone is secreted by 



the preovulatory follicle is more recent, but 

 it comes from many sources. The possibility 

 was first suggested following the discoveries 

 that the beginning of mating behavior 

 (Dempsey, Hertz and Young, 1936) and the 

 decrease in tissue uterine fluid (Astwood, 

 1939) , which depend on the presence of small 

 amounts of progesterone, coincide with the 

 beginning of the preovulatory swelling. 

 More recently, progesterone has been found 

 in the follicular fluid from sows, cows, and 

 the human female, and, in small quantities 

 in blood plasma of the rabbit, human female, 

 and rhesus monkey during the follicular 

 phase of the cycle (Duy vene de Wit, 1942 ; 

 Forbes, 1950, 1953; Bryans, 1951; Kauf- 

 mann, 1952; Edgar, 1953b; Buchholz, Dib- 

 belt and Schild, 1954; Zander, 1954). 



Earlier in this section it was noted that 

 there is much evidence from both histo- 

 chemical and the older morphologic studies 

 that theca interna, interstitial tissue, and 

 luteal cells, and to a lesser extent, granulosa 

 cells secrete the ovarian steroid hormones. 

 Many who have used histochemical methods 

 still feel that, even though these methods 

 demonstrate steroids and their precursors, 

 the reactions are not sufficiently specific for 

 identification of the individual hormones. 

 Others, however, have been more confident, 

 and when the evidence they have presented 

 is combined with that reported in some of 

 the more conventional morphologic studies 

 the following summarization of opinion 

 seems justified. Granulosa cells of the fol- 

 licles and granulosa lutein cells of the cor- 

 pora lutea contain progesterone or a pre- 

 cursor and secrete this hormone (Nishizuka, 

 1954; Green, 1955). Cells of the theca in- 

 terna, theca lutein cells, and interstitial cells 

 are believed to secrete estrogen and possibly 

 androgen (Corner, 1938; Deanesly, 1938a; 

 Pfeifter and Hooker, 1942; Hernandez, 1943; 

 Claesson and Hillarp, 1947a, b; Rocken- 

 schaub, 1951 ; Aron and Aron, 1952; Furuh- 

 jelm, 1954; Nishizuka, 1954; Fetzer, Hille- 

 brecht, Muschke and Tonutti, 1955; John- 

 son, 1958). The interstitial cells have been 

 the object of much study and will be given 

 especial attention. 



Interstitial tissue or cells in the ovary is 

 not as clear a concept as it is in the teste.-. 

 In the latter interstitial or Leydig cells are 

 derivatives of connective tissue elements 



