PHYSIOLOGY OF ANTERIOR HYPOPHYSIS 



247 



Fraenkel-Conrat, Li, Simpson and Evans, 

 1940). This function is most clearly demon- 

 strated by the injection of LH into hy- 

 pophysectomized, immature male rats after 

 liyi)ophyseal deficiency has resulted in 

 marked testicular atrophy. In these animals 

 the shrunken, spindle-shaped, and cyto- 

 chemically empty cells of Leydig are quickly 

 restored to the swollen, epitheloid, lipid-rich 

 type. The lipoid vacuoles exhibit histo- 

 chemical reactions that are characteristic 

 of, but not necessarily specific for, steroidal 

 substances. More specifically, the seminal 

 vesicles, prostate and Cowper's glands un- 

 dergo enlargement and each elaborates its 

 special exocrine secretion in proof of in- 

 duced testicular endocrine function. The 

 testes also enlarge somewhat, due to swelling 

 of the tubules and some minimal stimulation 

 of their spermatogenic epithelium. The lat- 

 ter response is believed to be brought about 

 by the direct spermatogenic action of testos- 

 terone per se and can, in fact, be dupli- 

 cated by the injection of this hormone alone. 

 In hypophysectomized adult male rats 

 given LH from the time of operation, the 

 entire reproductive system, including all 

 components of the testes, is maintained in 

 a normal condition (Greep and Fevold, 

 1937). Here it is presumed that the action 

 of LH is confined to stimulation of the inter- 

 stitial cells, because all other aspects of the 

 response can be dujilicated by exogenous 

 androgens. 



4. An Extragonadal Activity 



The possibility that gonadotrophins have 

 an effect on the adrenal cortex has always 

 been attractive. However, only in the mouse 

 has any clear-cut action been demonstrated. 

 LH has a trophic influence on the so-called 

 X-zone in the adrenal glands of mice (Ches- 

 ter Jones, 1949) . This zone of highly eosin- 

 ophilic cells is present at birth and disap- 

 pears at puberty in the males and during the 

 first gestation in females. Chester Jones 

 (1950) found that although the zone per- 

 sists after hypophysectomy in prepubertal 

 mice, the cells therein revert to an atrophic 

 state. It seemed likely, then, that the zone 

 might be responsive to a factor from the 

 pituitary. A check of available preparations 

 revealed that extracts rich in LH were 

 markedly trophic to the X-zone. Neither 



FSH nor ACTH had any beneficial action 

 in this regard. These findings fit nicely with 

 the fact that the X-zone reappears after 

 castration of postpubertal male mice (How- 

 ard, 1939) , i.e., at a time when the secretion 

 of LH is greatly increased (for a review see 

 Chester Jones, 1955, 1957). 



5. FSH and LH in Relation to Estrogen 



Secretion 



The relation of FSH to estrogen secretion 

 by the ovary has not been fully elucidated. 

 Present knowledge in this area is deficient 

 mainly because there has been little oppor- 

 tunity to study the activity of FSH as an 

 entity free of LH with which it exhibits 

 synergism. Acting with but minute amounts 

 of LH, the quantitative responses to FSH 

 are considerably enhanced as determined 

 by the growth response of the female gonad 

 (reviewed by Fevold, 1939, and by Evans 

 and Simpson, 1950), yet the qualitative 

 nature of the response may not be altered 

 (Fraenkel-Conrat, Li, Simpson and Evans, 

 1941). To the extent of present knowledge, 

 biologically pure FSH does not elicit the 

 secretion of estrogen by the ovary of the 

 hypophysectomized rat, and there is con- 

 vincing evidence that it also does not evoke 

 the secretion of androgen by the testes of 

 similarly operated animals (Fevold, 1939; 

 Greep, van Dyke and Chow, 1942; Evans 

 and Simpson, 1950; Simpson, Evans and Li, 

 1950; Simpson, Li and Evans, 1951). How- 

 ever, FSH does play an essential and pos- 

 sibly even a primary role in the promotion 

 of estrogen secretion by the ovary, inasmuch 

 as it prepares the follicular apparatus on 

 which LH can act to promote estrogen pro- 

 duction. That the injection of highly puri- 

 fied FSH preparations into intact, immature 

 rats and mice (Moon and Li, 1952; Thomo- 

 poulou and Li, 1954) has evoked the se- 

 cretion of estrogen is explicable, perhaps, on 

 the basis of endogenous LH release. 



6. FSH and LH, Interactions 



LH is believed to interact in some man- 

 ner with FSH at the ovarian level to pro- 

 duce greater stimulation than could be 

 expected on the basis of the sum of the 

 separate actions of these hormones. This ef- 

 fect has also been termed synergism or ]'»o- 

 tentiation. It is a real and striking phenor.u'- 



