450 



PHYSIOLOGY OF GONADS 



disappointment that has been expressed. 

 First, the purification and synthesis of the 

 hormones in the 1930's (Allen, 1939; Doisy, 

 1939) and the later successful development 

 of synthetic estrogens and gestagens ( Solms- 

 sen, 1945; Dodds, 1955; Rock, Garcia and 

 Pincus, 1956; St. Whitelock, 1958) provided 

 a means whereby much of ovarian physi- 

 ology could be studied out of context with 

 the processes by which this organ functions. 

 Specifically, there are many effector actions 

 of ovarian hormones, many interrelation- 

 ships with other hormones and with each 

 other, many problems of tissue responsive- 

 ness, and many questions bearing on proc- 

 esses of ovarian hormone metabolism, all of 

 which can be studied in ovariectomized ani- 

 mals. 



Secondly, there were many practical rea- 

 sons why chemists should have striven to 

 synthesize estrogenic substances and gesta- 

 gens which are suitable for replacement 

 therapy. Once prepared, these synthetic sub- 

 stitutes are of interest, but their develop- 

 ment and therapeutic application may well 

 have diverted attention from studies of the 

 ovary. 



If there is disappointment with tlie prog- 

 ress that has been recorded, we would direct 

 attention to substantial accomplishments 

 which should stand us in good stead in the 

 future. Among these are the numerous care- 

 ful descriptions of the growth and matura- 

 tion of ovarian follicles and the meticulous 

 accounts of corpus luteum formation, struc- 

 ture, and involution. In a general way it has 

 become clear that in many species estrogen 

 and progesterone are produced while the 

 follicles are maturing, and that, during the 

 functional life of the corpus luteum, pro- 

 gesterone and estrogen are secreted. Esti- 

 mates of the amounts produced have been 

 numerous and of more than ordinary in- 

 terest. In addition, they probably represent 

 steps toward the determination of additional 

 important information : the day-to-day rate 

 of production correlated with the growth of 

 the follicles and the development of the 

 corpora lutea, and, in species in which 

 variable numbers of follicles and corpora 

 lutea develop, steps in an effort to ascertain 

 whether, for example, 10 follicles in an in- 

 dividual produce more hormone than 5. 

 This knowledge, if we possessed it, might 



contribute significantly to current theories 

 of gonadal-pituitary relationships because 

 thresholds are involved in the regulatory 

 processes <see chapters by Everett and 

 Greep ) . 



It could be disappointing that, on the 

 basis of evidence which is largely circum- 

 stantial and inferential, almost every tissue 

 component of the ovary, membrana granu- 

 losa, theca interna, and interstitial cells, 

 has been claimed to be the source of estro- 

 gen and progesterone. But it is encouraging 

 that information has been obtained which 

 prompts us to recognize that it may be futile 

 and unrealistic to attempt to identify spe- 

 cific cell types as the sources of hormones 

 in the ovary. Current thought, stimulated 

 by the discovery that testicular cells, pla- 

 cental tissue, and occasionally the adrenal 

 cortex are sources of estrogen and proges- 

 terone, and that ovarian tissue produces 

 androgens, is leaning toward the view that 

 the several tissues involved in steroid hor- 

 mone biosynthesis may be subject to meta- 

 bolic aberrations which change their hor- 

 mone production either in rate or in kind. 

 The a])i)roach to the problem now seems to 

 be through enzymatic biochemistry rather 

 than through gross or finer morphology. Ex- 

 amples of this approach which are sug- 

 gestive for further work on the ovaries are 

 jirovided by the numerous studies by Sam- 

 uels and his associates (Samuels, Helmreich, 

 Lasater and Reich, 1951 ; Huseby, Samuels 

 and Helmreich, 1954; Beyer and Samuels, 

 1956; Samuels and Helmreich, 1956; Slaun- 

 white and Samuels, 1956). 



It is known in a general way that fol- 

 licular maturation, ovulation, and corpus 

 luteum formation are controlled by gonado- 

 troi)hic hormones from the pituitary. How- 

 ever, as Greep emphasizes in his chapter, 

 the specific gonadotrophic hormones have 

 not yet been isolated and identified, nor 

 have their specific roles in ovarian physi- 

 ology b(»en demonstrated. To be sure, ovu- 

 lation has been repoited following the 

 injection of allegedly purified pituitary 

 gonadotrophins into hypojihysectomized 

 rats (Velardo, 1900), but until stages nor- 

 mally seen ill the jn'ocess of folliculogenesis 

 and ()\-ulati()ii can he rejn'oduced consist- 

 ently by the use of pituitary gonadotro- 

 I)hins, and until target organ responses simi- 



