MAMMALIAN OVARY 



477 



to secrete hormones, both estrogen and 

 progesterone, in amounts which are in ex- 

 cess of those secreted by untreated animals. 

 The secretion of these hormones was ele- 

 vated in rats, mice, and hamsters by the 

 implantation of whole pituitaries (Smith 

 and Engle, 1927 » or by the administration 

 of chorionic gonadotrophin (Price and Ortiz, 

 1944; Ortiz, 1947; Green, 1955). The re- 

 activation of senile ovaries was first demon- 

 strated by Zondek and Aschheim (1927) 

 following the insertion of hypophyseal im- 

 jilants, and later by numerous other in- 

 vestigators listed in the review of the subject 

 l)y Tlmng, Boot and Miihlbock (1956). In 

 more recent experiments an enhanced secre- 

 tion of estrogen and progesterone followed 

 the injection of old hamsters with chori- 

 onic gonadotrojihin (Peczenik, 1942; Ortiz, 

 1955). 



In women fertility may be lost before 

 the menopause (Engle, 1955). Studies in 

 progress at Iowa (Bradbury, personal com- 

 munication) show that urinary gonado- 

 troi')hins may be elevated before the meno- 

 pause and the last ovarian cycles are 

 achieved in the presence of excessive 

 amounts of pituitary gonadotrophin. As a 

 rule the human ovary is devoid of oocytes 

 and produces relatively little estrogen at 

 the time of the menopause. Frequently, how- 

 ever, there is enough residual ovarian ac- 

 tivity (estrogen production) to maintain the 

 vaginal epithelium for 10 to 15 years after 

 tlie menopause. These observations on 

 women suggest that as the supply of oocytes 

 l)ecomes depleted, less estrogen is produced 

 and more gonadotrophin is released to 

 stimulate the aging ovary. This secjuence 

 is in harmony with the concepts of Dubreuil 

 (1942) and Hisaw (1947), because with 

 fewer areas of granulosa there would be 

 fewer centers of organizer to bring al)out 

 the differentiation of thecal tissue competent 

 to produce estrogen. 



Ovarian stromal hyperplasia has been 

 found in association with endometrial hy- 

 perplasia after the menopause (Morris and 

 Scully, 1958). Sherman and Woolf (1959) 

 suggested that the postmenopausal ovary 

 may produce abnormal sexogens which 

 bring about an endometrial proliferation 

 and ultimately adenocarcinoma of the endo- 

 mi'trium. Their urinarv l)ioassay studies 



indicate that the patients were excreting 

 ICSH-type gonadotrophin. The observa- 

 tion has been made at Iowa that a few 

 postmenopausal women with endometrial 

 carcinoma were maintaining an estrogenic 

 vaginal epithelium when they were ovari- 

 ectomized at ages varying from 65 to 70 

 years. Subsequently the gonadotrophin ex- 

 cretion increased to the ciuantities usually 

 seen after the menopause. In these unusual 

 cases the aging ovaries produce estrogen, or 

 possibly estrogen and androgen, in quanti- 

 ties sufficient to suppress the usual excess 

 production of gonadotrophins. 



The responsiveness or sensitivity of the 

 ovary to gonadotrophic stimulation is not 

 constant throughout the life of an indi- 

 vidual. If we may judge from the studies 

 of Corey (1928) and Selye, Collip and 

 Thomson (1935) on newborn and 10- to 

 15-day-old rats, Moore and Morgan (19431 

 on young opossums, and Price and Ortiz 

 (1944) and Ortiz (1947) on rats and ham- 

 sters, the prepubertal period is characterized 

 by very rapid and great increases in re- 

 sponsiveness to gonadotrophic stimulation. 

 Species differences are great. The opossum 

 ovaries do not respond to gonadotrophic 

 stimulation until about 100 days of age 

 (Moore and Morgan), whereas responsive- 

 ness was first detected in the rat ovary at 

 4 to 10 days (Price and Ortiz) and in the 

 hamster ovary by the 10th day (Ortiz). 

 Such data, coupled with the appearance of 

 the ovaries at birth, would seem to exclude 

 the possibility of gonadotrophic stimula- 

 tion during the prenatal period, and per- 

 haps the capacity for being stimulated as 

 well. 



Certain other species are different and 

 present problems. There is an extensive fol- 

 licular development and luteinization in 

 the fetal ovaries of the giraffe which is the 

 basis for the suggestion that the ovaries of 

 this species are responsive to gonadotrophin 

 before birth (Amoroso, 1955). Such a con- 

 clusion is predicated on the assumption ei- 

 ther that serum gonadotrophin crosses the 

 placental membrane or that the fetal pitui- 

 tary secretes gonadotrophin. Neither hy- 

 pothesis has been proved. Evidence exists 

 that the ovaries of the horse and seal are 

 strongly stimulated before birth (Cole, 

 Hart, Lyons and Catchpole, 1933; Amoroso, 



