250 



HYPOPHYSIS AND GONADOTROPHIC HORMONES 



species have not been encouraging. Intensive 

 treatment with prolactin has singularly 

 failed to prolong the functional life of the 

 corpus luteum in monkeys (Hisaw, 1944; 

 Bryans, 1951) and women (Holmstrom and 

 Jones, 1949, Bradbury, Brown and Gray, 

 1950). By administering prolactin along 

 with HCG during the postovulatory phase of 

 the cycle in regularly menstruating women, 

 Fried and Rakoff (1952) prolonged the func- 

 tional life of the corpus luteum up to 13 days 

 but neither hormone given alone was effec- 

 tive. These findings suggest that LTH may 

 only act in synergism with a luteinizing hor- 

 mone in man. 



By recent demonstration, the lactogenic 

 hormone appears to have a luteotrophic 

 action in sheep (Moore and Nalbandov, 

 1955j. The corpora lutea of anestrous ewes, 

 ovulated with pregnant mare serum gon- 

 adotrophin, were maintained in a functional 

 state for 20 to 30 days by daily injections 

 of 200 I.U. of prolactin. Without such 

 treatment the newly ovulated corpora lutea 

 regressed rapidly. However, since the pro- 

 lactin-treated animals were intact and their 

 ovaries were heavily luteinized, the authors 

 could not be certain that the prolongation 

 of the functional life of the corpora lutea 

 was attributable solely to the injected hor- 

 mone. The testing of LTH in the recently 

 ovulated and hypophysectomized rabbit 

 (which seems not to have been done) would 

 furnish valuable basic information. 



3. Detection and Assay of Prolactin Activ- 

 ity 



Luteotrophic hormone produces no con- 

 spicuous morphologic changes in the mam- 

 malian ovary; the response can in fact only 

 be detected by demonstrating that pre- 

 formed corpora lutea are functional. Luteo- 

 trophic activity per se, therefore, cannot be 

 estimated directly in mammals, but rests 

 on the evocation of progesterone secretion so 

 that tests for LTH (reviewed by Astwood, 

 1953) are, in effect, tests for progesterone. 

 Thus in the appropriately prepared rat I^TH 

 activity can be demonstrated qualitatively 

 and a rough estimate of potency made by 

 the appearance of deciduomas (Astwood, 

 1939, Lyons, Li, Johnson and Cole, 1953), 

 maintenance of early gestation (Cutuly, 

 1941, and 1942). interruption of estrous 



cycles (Desclin, 1949; ]\Iayer and Canivenc, 

 1951 j, and appearance of diestrual smears 

 in HCG-treated hypophysectomized rats 

 (Astwood, 1941; van der Kuy, van Soest 

 and van Prooye-Belle, 1953) . In other mam- 

 mals tests for LTH likewise hinge on the 

 demonstration of some progesterone-like 

 effect; these vary with the species (Cowie 

 and Folley, 1955). 



In practice the assumption is made that 

 prolactin and luteotrophin are identical, 

 and luteotrophic preparations are assayed 

 by measurement of their capacity to stimu- 

 late the pigeon crop sac as determined by 

 either the "systemic crop weight" method 

 introduced by Riddle, Bates and Dykshorn 

 (1933) or the "local micromethod" of Lyons 

 and Page (1935). Modifications have been 

 introduced in the "weight" method by 

 Clarke and Folley (1953), and in the 

 "local" method by Lyons (1937) and Reece 

 and Turner (1937). (For detailed review of 

 assay literature see White, 1949, or Cowie 

 and Folley, 1955.) 



III. Pituitary Gonadotrophic Hormone 



Content and Related Evidence of 



Secretory Activity 



A valuable method of studying the phys- 

 iology of the pituitary gland is to remove 

 it at autopsy or by surgery and ascertain 

 the nature and quantity of gonad-stimulat- 

 ing hormone activity residual within the 

 gland as shown by the gonadal response 

 elicited in some appropriate recipient test 

 animal, i.e., immature rat, mouse, chick, 

 pigeon. Early investigators relied mainly on 

 imjilanting the fresh gland or injecting 

 minced tissue, but this procedure is quanti- 

 tatively unreliable inasmuch as the tissue 

 tends to remain viable for an indeterminate 

 time (Hellbaum and Greep, 1940). This 

 ^difficulty was obviated by freezing (Fraen- 

 jkel-Conrat, Simpson and Evans, 1940a) or 

 iby desiccating the glands in acetone fol- 

 lowed by trituration in water or saline. As 

 an alternative procedure, the pituitary 

 glands of small animals can be crushed be- 

 tween glass slides, then speedily air-dried 

 and recovered as a powder, without loss of 

 potency (Kupperman, Elder and Meyer, 

 1941). Others preferred to test fresh ground 

 homogenate of the pituitary tissue. 



Pituitary gonadotrophic jiotency, a repre- 



