248 



HYPOPHYSIS AND GOXADOTROPHIC HORMONES 



non, for which no satisfactory explanation 

 is available. The principle of potentiation 

 has been employed extensively to intensify 

 artificially induced gonadal stimulation in 

 sheep and cattle (Hammond, Jr. and Parkes, 

 1942; Casida, Meyer, McShan and Wis- 

 nicky, 1943). 



An interplay between FSH and LH seems 

 to operate in the accomplishment of ovula- 

 tion. The ovulatory response to LH is well 

 known to be intensified when acting in 

 conjunction with FSH (Foster, Foster and 

 Hisaw, 1937; Pincus, 1940; Chang, 1947a, b; 

 Hisaw, 1947; ISlarden, 1952). The reader is 

 referred to Hisaw (1947) for a thoughtful 

 analysis of the literature. FSH acting alone 

 in hypophysectomized animals will bring 

 follicles to maturity, but seldom does it lead 

 to their rupture (Knobil, Kostyo and Greep, 

 1959). LH, on the contrary, given as a quick 

 acting stimulus in the presence of ripe fol- 

 licles, is an efficient ovulator. Inasmuch as 

 the exact nature of the ovulatory stimulus 

 has not been elucidated, the term "ovula- 

 tory hormone" has been widely used. It 

 has the advantage of being less committal as 

 to the nature of the factors operating. In 

 reality, it would be a very difficult matter to 

 test the ovulating capacity of LH in the 

 complete absence of FSH, since only near- 

 mature follicles can be ovulated, and their 

 existence is dependent on the action of FSH. 



Rapid involution and disappearance of 

 persisting corpora lutea in hypophysecto- 

 mized adult rats (Bunde and Greep, 1936; 

 Greep, 1938) was induced by injecting im- 

 pure LH extracts and combinations of FSH 

 and LH. Although pure LH did not produce 

 the histolytic response, it is worth noting 

 that it also did not elicit any maintenance 

 of hiteal function (Greep, van Dyke and 

 Chow, 1942 ». 



When FSH and LI I were adniinistered 

 concurrently to intact or hypophysecto- 

 mized, immature male rats a synergism was 

 noted in respect to the increase in weight of 

 the testes (Greep, Fevold and Hisaw, 193(31. 



7. Assay 



Several means are available for detecting 

 the activity of LH, but no one has proved 

 fully satisfactory as a means of quantifying 

 this hormone. Oldest of these methods is 



the augmentation and luteinization test, as 

 developed in the laboratory of Fevold and 

 Hisaw. It involved a comparison of the 

 qualitative ovarian response of intact, im- 

 mature female rats to FSH alone as opposed 

 to that of animals receiving FSH and LH 

 simultaneously. A positive test for LH was 

 manifest by augmentation of the ovarian 

 weight and induction of extensive luteiniza- 

 tion, resulting in what has often been 

 termed "mulberry ovaries." When hypophy- 

 sectomized test animals were employed, the 

 results were less striking both quantitatively 

 and qualitatively, but interference by en- 

 dogenous LH was precluded. 



The possibility of using the weight in- 

 crease of the accessory sexual structures in 

 immature male rats as a test for LH sug- 

 gested itself from studies of the effects of 

 the separate gonadotrophins in male ani- 

 mals. The ventral lobe of the prostate was 

 the most sensitive. Employing hypophy- 

 sectomized animals and pure LH, Greep, 

 van Dyke and Chow (1941) demonstrated a 

 satisfactory dose-response relationship. The 

 test is simple, ofi'ers an objective measure- 

 ment, and is moderately sensitive. It has 

 the disadvantage of being indirect — the 

 prostate response is androgen-mediated and 

 reflects the action of LH on the testicular 

 Leydig cells. The specificity of the prostate 

 test for LH has been questioned by Segaloff, 

 Steelman and Flores (1956). Pursuant to a 

 report by Grayhack, Bunce, Kearns and 

 Scott (1955) that jirolactin enhanced the 

 ventral j^rostate response to testosterone in 

 castrated rats, Segaloft" and his colleagues 

 reported that prolactin sensitized the ven- 

 tral prostate to the action of androgen se- 

 creted in response to LH. Lostroh and Li 

 (1956) were not able to confirm that pro- 

 lactin synergizes with testosterone, and 

 Lostroh, Squire and Li (1958) found a 

 strain variation with respect to the specific- 

 ity of the ventral prostate as a test for 

 ICSH. Wlien the Long-Evans strain of rats 

 was used, neither prolactin nor growth hor- 

 iiionc. or any combination of these, altered 

 the prostatic response to exogenous ICSH; 

 with the Sj)raguc-Dawley strain both 

 growth hormone and lactogenic hormone 

 effected significant enhancement of the re- 

 sponse to ICSH. It seems that hypophysec- 



