PHYSIOLOGY OF ANTERIOR HYPOPHYSIS 



245 



pensatory hypertrophy which is elicited by 

 unilateral gonadectomy, a response that is 

 l)riniarily elicited by FSH. The observation 

 by Carmichael and Marshall (1908) that 

 unilateral ovariectomy leads to compensa- 

 tory hypertrophy of the remaining ovary is 

 now commonplace. Similar experiments on 

 tiie male were not reported until 1940 (Addis 

 and Lew). Compensatory gonadal hyper- 

 t rophy is much less pronounced in the male ; 

 the 50 per cent of testis mass remaining 

 after unilateral gonadectomy increases only 

 to 56 per cent of the weight of paired gonads 

 of comparable controls, whereas the ovary 

 increases up to 70 per cent. Clearly, in no 

 instance is all the lost tissue regained 

 through compensatory hypertrophy. It is of 

 incidental interest in this connection that 

 Edwards (1940) showed that unilateral cas- 

 tration in adult male animals leads to a 

 halving of the sperm count. In the uni- 

 laterally ovariectomized female it is well 

 established that the opposite ovary sheds 

 at each ovulation the full number of eggs 

 characteristic of the species (Asdell, 1924; 

 Brambell, 1956). It is also of interest that 

 in the unilaterally spayed rat the number 

 of primary oocytes remains at the level nor- 

 mal for one ovary (Mandl and Zuckerman, 

 1950), indicating that FSH, as suggested 

 by most older studies, does not influence 

 ovogenesis. 



5. Assay 



In recent years the ability of FSH to 

 synergize with human chorionic gonado- 

 trophin {HCCPr has been utilized in the 

 development of methods for the bioassay of 

 FSH. The end point is weight of ovaries 

 from immature rats (Evans and Simpson, 

 1950; Steelman and Pohley, 1953) or mice 

 (Brown, 1955) which have also been in- 

 jected with a constant and substantial 

 amount of HCG. These methods are more 

 sensitive than other, older assay procedures 

 involving ovarian weight increase following 

 injection of FSH alone into immature, in- 

 tact rats or mice, but they are less specific 

 than the assay based on ovarian weight in- 

 crease (Evans, Simpson, Tolksdorf and Jen- 

 sen, 1939) or re-establishment of minimal 

 follicular growth (histologic) in hypophy- 

 sectomized immature rats (Evans and 

 Simpson, 1950). The methods of Steelman 



and Pohley and of Brown have clear ad- 

 vantages over the indirect assay based on 

 the weight of the uteri in FSH-injected, 

 intact, immature mice as introduced by 

 Klinefelter, Albright and Griswold (1943). 



Testis weight increments in hypophy- 

 sectomized male rodents serve as a con- 

 venient measure of FSH activity, provided, 

 however, that the FSH is biologically pure 

 (Greep, van Dyke and Chow, 1940; Simp- 

 son, Evans and Li, 1950) . 



The activity of FSH in an aqueous me- 

 dium is known to be augmented by a variety 

 of substances. The explanation of the ef- 

 fectiveness of these cofactors is unknown, 

 but several of them such as heme (McShan 

 and Meyer, 1941) and zinc and copper salts, 

 probably merely delay absorption and pro- 

 vide a more sustained effective blood level 

 of the hormone. 



B. LUTEINIZING HORMONE (INTERSTITIAL 

 CELL-STIMULATING HORMONE ) 



1. Chemical Features 



Working independently, Li, Simpson and 

 Evans (1940a, b) and Shedlovsky, Rothen, 

 Greep, van Dyke and Chow (1940) isolated 

 LH from sheep and swine pituitaries, re- 

 spectively. The two preparations have simi- 

 lar physiologic properties (Greep, van Dyke 

 and Chow, 1942; Simpson, Li and Evans, 

 1942a, b ) , but they differ chemically (Chow, 

 van Dyke, Greep, Rothen and Shedlovsky, 

 1942) and are distinguishable by immuno- 

 logic methods (Chow, 1942). The sheep hor- 

 mone had an isoelectric point of 4.6 and a 

 molecular weight of 40,000, whereas that of 

 swine had an isoelectric point of 7.45 and a 

 molecular weight of 100,000. Ellis (1958) 

 has recently achieved a considerable con- 

 centration of LH activity, using cation ex- 

 change resins. Squire and Li (1959), using 

 a modified extractive procedure, chromato- 

 graphic separation, and zone electrophoresis 

 on starch, obtained tw^o equally active 

 "ICH" proteins; one of these, "^-ICH," 

 has been partially characterized: it has an 

 isoelectric point near 7.3 and a molecu- 

 lar weight (calculated) of approximately 

 30,000. This fraction had "a high degree of 

 homogeneity," showed no evidence of con- 

 tamination with other pituitary hormones, 

 and was active by the ventral prostate test 

 at a total dose of 0.5 /xg. 



