PHYSIOLOGY OF ANTERIOR HYPOPHYSIS 



267 



the pituitary nearly vanishes. In the human 

 male the excretion of urinary gonadotro- 

 phins is sharply reduced. 



D. EFFECT OF ESTROGEN ON LUTEINIZING 



HORMONE AND LUTEOTROPHIN 



HORMONE SECRETION 



An important consideration in assessing 

 the action of steroids on pituitary function 

 is the effect these have on the output of the 

 luteinizing hormone. In most of the prior 

 discussion reference to inhibition of gonado- 

 trophin secretion has been to that of FSH. 

 The assumption that estrogen acts in some 

 manner to elicit a more effective luteinizing 

 stimulus from the pituitary appears in 

 nearly all papers dealing with pituitary- 

 gonadal relationships. It constitutes a key 

 point in all theories so far advanced to ex- 

 plain sexual periodicity in the female. The 

 idea that estrogen may act to release LH 

 originated with the "Hohlweg effect." This 

 author (1934) found corpora lutea appear- 

 ing in the ovaries of immature rats as the 

 result of a single injection of estrogen. This 

 response has not been obtained by other 

 workers (Bradbury, 1947; Greep and Ches- 

 ter Jones, 1950aj using 21-day-old imma- 

 ture rats. It seems that the response is ob- 

 tained only if the rats are nearing sexual 

 maturity (Burrows, 1949). In adult rats 

 massive daily doses of estrogen induce a 

 type of pseudopregnancy and have a de- 

 cided effect on the corpora lutea; they in- 

 crease inxsize to resemble corpora lutea 

 gravidari, and-~ai'e functional as shown by 

 their ability to maintain diestrous vaginal 

 smears for 3 weeks in face of heavy estrogen 

 treatment (Merckel and Nelson, 1940). To 

 what extent such changes are due to LH or 

 LTH, or both, is not clear. It might be ex- 

 pected that the large amount of estrogen 

 would suppress LH secretion. If this were 

 the case, continued LTH secretion would 

 be independent of estrogen titers and, fur- 

 thermore, would be capable of both main- 

 taining and evoking secretion from the 

 corpus luteum. In the rat, at least, this 

 seems to be consonant with the capacity of 

 pituitary homografts to secrete LTH se- 

 lectively (Everett, 1956). Hellbaum and 

 Greep (1940, 1943) noted that the pitui- 

 taries of castrated rats treated with estro- 



gen for more than 20 days gradually lost 

 their LH potency. They presumed that the 

 LH component was released, but they were 

 not able to detect it in the bloodstream with 

 certainty. Greep and Chester Jones (19501)1 

 tried to demonstrate by several means an 

 LH-releasing action of estrogen in intact 

 and gonadectomized rats of both sexes, but 

 were forced to the conclusion that the funda- 

 mental effect of estrogen on the pituitary 

 appeared to be to reduce the synthesis and 

 storage of LH. A further point against the 

 concept that estrogen triggers off an out 

 l^ouring of LH from the pituitary is the 

 fact that no sudden upsurge in LH activity 

 has been observed in the male by an injec- 

 tion of estrogen, as judged by the condition 

 of the testicular Leydig cells or by the size 

 and histologic appearance of the ventral 

 prostate. 



There is evidence, however, favoring the 

 concept that estrogen promotes release of 

 LH. Funnell, Keaty and Hellbaum (1951) 

 administered estrogen to a selected group of 

 patients manifesting classical menoj^ausal 

 symptoms and were able to demonstrate LH 

 activity in the urine where previously only 

 FSH activity had been detectable. Con- 

 firmatory results ha\-e been reported by 

 Brown (1956, 1959) using patients with 

 secondary amenorrhea. 



The relation of estrogen to ovulation 

 bears on the purported LH-releasing action 

 of this substance. Everett, Sawyer and 

 Alarkee (1949) succeeded in hastening ovu- 

 lation in normal cycling rats by a properly 

 timed injection of estrogen, but the re- 

 sponse is not specific inasmuch as other 

 substances, including progesterone, can pro- 

 duce the same effect. The work of Everett 

 (1948) and co-workers (for review see his 

 chapter in this book) suggests that estrogen 

 may act on the anterior hypophysis in- 

 directly through some neural, conceivably 

 hypothalamic, mechanism. Estrogens have 

 been used with variable, but generally poor, 

 success in promoting ovulation. The fact 

 that the estrous rabbit does not ovulate in 

 response to injected estrone (Bachman, 

 1935) is not considered critical evidence, 

 since ovulation in this species normally in- 

 volves neural excitations associated with 

 mating. More decisively the persistent- 



