4(36 



PHYSIOLOGY OF GONADS 



parabiosi;? with a castrate partner become 

 hypertrophied and produce enougli andro- 

 gen to stimulate prostatic tissue (Jolmson, 

 1958) ; associated with the condition is an 

 unusual thecal and interstitial tissue hyper- 

 trophy. The masculinizing features of the 

 Stein-Leventhal syndrome ( polycystic 

 ovary) have been attributed to the presence 

 of androgens, having their source perhaps 

 in the hilar cells of the ovaries (Lisser and 

 Traut, 1954) , but the action of other steroids 

 with masculinizing properties also has been 

 suggested (Fischer and Riley, 1952). The 

 latter possibility might well be checked in 

 any case when the production of androgens 

 by the ovary is suspected. 



Estrogen and progesterone are the ovarian 

 hormones whose action in the female has 

 been studied the most extensively. The steps 

 which led to their extraction and chemical 

 identification were described by Doisy and 

 by Willard Allen in the 1932 and 1939 edi- 

 tions and will not be repeated here. Atten- 

 tion, however, will be directed to the iso- 

 lation and identification of several naturally 

 occurring gestagens in addition to progester- 

 one (Davis and Plotz, 1957; Zander, Forbes, 

 von Miinstermann and Neher, 1958). These 

 are metabolic degradation products which 

 still retain progestational activity. 



Now as in the period 1932 to 1939, there 

 are many unsolved problems, but it is 

 equally true that much of interest and value 

 has been learned. Not the least of these con- 

 tributions has been the clarification of the 

 l)athways of their biosynthesis (see chapter 

 by Villeej . In the sections which follow par- 

 ticular attention will be given to the prob- 

 lem of their origin, to the rate of production, 

 the manner of transport and storage, and to 

 their "half-life." 



A. CELLULAR ORTOIX 



As Villee points out in his chajiter, estro- 

 gen and progesterone are apparently de- 

 rived from cholesterol by a series of chemi- 

 cal changes. Within the ovary and in the 

 corpora lutea of rats, there is a definite re- 

 duction in the concentration of ascorbic acid 

 and cholesterol after gonadotrophin admin- 

 istration. These changes have been consid- 

 ered (ividence for tiie activation of hormone 

 synthesis (Everett, 1947; Miller and Ever- 

 ett, 1948; Levin and Jailer, 1948; Aldman, 



Claesson, Hillarp and Odeblad, 1949; Claes- 

 son, Hillarp, Hogberg and Hokfelt, 1949; 

 Noach and van Rees, 1958). 



Efforts to identify the cell types in which 

 these processes take place have not been al- 

 together successful. We have noted, for ex- 

 ample, that several tissues such as testis,, 

 placenta, and occasionally the adrenal cor- 

 tex can produce estrogen. These are tissues,, 

 then, which produce more than one hormone. 

 Gardner emphasized this during a discus- 

 sion of Parkes' (1950) review of androgenic 

 activity of the ovary, when he called atten- 

 tion to Dr. Furth's observations that some 

 ovarian tumors possess potentialities for bi- 

 sexual hormone production. About the same 

 time, Shippel (1950) postulated that thecal 

 cells may be a source of estrogen and andro- 

 gen and that the type of hormone produced 

 may depend on particular stresses or stim- 

 uli. On the other hand, many investigators,, 

 and particularly those interested in the ap- 

 jilication of histocheraical procedures,^ have 

 l^roceeded under the assumption that there 

 are tissues of the ovary in which one hor- 

 mone is iH'oduced predominantly. They 

 found, for example, that the reactions of fol- 

 licular granulosa and theca cells are strik- 

 ingly different (Demi)sey and Bassett, 1943; 

 Dempsey, 1948; Shij^pel, 1950). To be sure, 

 the results w^iich have been obtained have 

 not led to agreement with respect to details, 

 but there is much evidence from the reac- 

 tions which have been described, as well as 

 from the older morphologic studies, that 

 tlieca interna, interstitial, and luteal cells 

 and, perhaps to a lesser extent, granulosa 

 cells, are active in steroid hormone synthe- 

 sis. What is less certain than the fact that 

 these cells, and consequently the ovaries, 

 produce estrogen, progesterone, and andro- 

 gen is their relative role compared with that 

 of other tissues. Presumably it is major; 

 nevertheless, evidence for the extra-ovarian 

 origin of estrogenic substances is provided 

 by the occurrence of cyclic vaginal activity 

 in ovariectomized animals (Kostitch and 

 Telebakovitch, 1929; Mandl, 1951; Veziris, 



"Dempsey and Bassett, 1943; Dempsey, 1948; 

 Claesson and Hillarp, 1947a-c ; Claesson, Diczfa- 

 hisy, Hillarp and Hogl)erg, 1948; McKay and Rob- 

 inson. 1947: Sliii)iH>l. 1950: Barker. 1951: Rocken- 

 scliauh. 1951: Wliite, Heitis, Rock and Adams. 

 1951: Deane. 1«)52: Fuiulue-lm, 1954: Xisliizuka. 

 1954. 



