Discussions 49 



It may not be an unimportant observation that the conditions most favorable for 

 folhcLilar development when induced by gonadotropins are also at the same time most 

 favorable for stimulating estrogen secretion. Both FSH and LH are notoriously 

 ineffective when given alone in dosages that are very effective when the two hormones 

 act concurrently. A notable difference between the two situations is that in the former 

 estrogen is not secreted and in the latter it is. The follicular growth produced by large 

 doses of FSH is probably facilitated by the weak LH action that is invariably present, 

 and also estrogen is secreted. 



The association of estrogen secretion with follicular growth seems to apply equally 

 well to ovarian responses induced by the chorionic luteotropin, HCG. This hormone is 

 capable of causing the secretion of both estrogen and progesterone provided follicles 

 and corpora lutea (particularly the latter) are present when it is administered. It 

 also can substitute for LH when FSH is given. However, it cannot promote follicular 

 growth, at reasonable dosage, in the involuted ovaries of hypophysectomized rats or 

 in the ovaries of juvenile monkeys, and in neither instance is estrogen secreted. 

 The probable importance of estrogen is suggested by the fact that the ovaries of 

 hypophysectomized rats will respond to HCG when the treatment is preceded by a 

 series of injections of estrogen. Also, estrogen will facilitate the action of FSH. 



Another placental hormone, PMS, is of interest in this connection in that it can mimic 

 both FSH and LH, particularly the former, and, of course, estrogen secretion is associ- 

 ated with its effects. It is an excellent hormone for producing follicular growth and is 

 useful in experimental ovulation. However, both it and HCG are, in reality, hormones 

 of gestation that are designed for the specific physiological needs of the species 

 in which they are found and are useful in studies of ovulation only in so far as 

 their pharmacological actions assist in the elucidation of the physiology of FSH 

 and LH. 



It may not be of direct practical importance for the problem in hand, but I do think 

 it adds interest to keep in mind that the interactions of pituitary and ovarian hormones 

 in the regulation of follicular development and ovulation, as found in vertebrate 

 animals, represent the culmination in the evolution of a long series of adaptations. 

 The present evidence indicates that in the vertebrates the hormonal situation is 

 basically the same in all reproductive cycles up to and including ovulation. The 

 principal hormones seem to be FSH, LH and estrogen. This means of course that 

 the cycle in all vertebrates is physiologically homologous with the follicular phase 

 of a mammalian estrous cycle. Also, it seems quite possible that the steroid hormone of 

 the Graafian follicle in all instances is estradiol-17p. This is supported by the isolation 

 of estradiol-17p from ovaries of such distantly related vertebrates as the mammal, 

 bird, lung fish and dogfish. It is also of added interest that estradiol- 17 [3 has been found 

 in the ovaries of certain invertebrates, i.e. a starfish, sea urchin and pecten. It is also 

 a possibility that progesterone is an ubiquitous steroid. A steroidal substance has been 

 obtained from the ovaries of invertebrates, by using methods applicable to mammalian 

 tissues, which has been tentatively identified as progesterone on the basis of column 

 chromatography, paper chromatography and positive Hooker-Forbes reactions. 



The general presence of these steroids raises the question of their importance and 

 function in the physiology of the follicle itself. When reduced to its simplest form, 

 it is conceivable that estrogens and progesterone along with various other steroids 

 and sterols were deposited in the ovum by the surrounding nurse cells or granulosa, 

 with which ova are commonly associated, long before they assumed hormonal functions. 

 It is not even necessary to assume that these compounds were synthesized and secreted 

 by the nurse cells. There is some evidence that they are present in plants and con- 

 sequently might have been obtained ready formed as is true of most vitamins. However, 

 regardless of origin, the most important point is the probability that the nurse cells 

 of the follicle from the inception of the practice of passing materials along to the ovum 

 were metabolically acquainted with steroid compounds and also it is a further 

 assumption that the initial endocrine functions were concerned only with physiological 

 processes in the follicle. The acquisition of the status of bodily hormones was probably 

 a specialization that came later. 



