1188 



HORMONAL REGULATION 



ing ovariectomy provides convincing evi- 

 dence for the importance of this organ in 

 lower mammals and in the infrahuman pri- 

 mates which have been studied (Ball, 1936; 

 Robson, 1938; Young and Orbison, 1944). 

 The experiments of Allen and Doisy (1923) 

 demonstrated that substances within the 

 Graafian follicle are directly responsible, but 

 a more complete understanding of the nature 

 of the relationship was obtained after puri- 

 fied preparations became available. It was 

 then shown that the display of the copu- 

 latory response and male-like mounting by 

 ovariectomized guinea pigs depends on the 

 subcutaneous^ injection of a relatively small 

 quantity of an estrogen followed after an 

 interval by the injection of a small amount 

 of progesterone (Dempsey, Hertz and 

 Young, 1936; Young and Rundlett, 1939 ». 

 An atypical response sometimes follows in- 

 jection of the estrogen, but restoration of 

 the behavior characteristic of the individual 

 before ovariectomy depends on supplemen- 

 tary treatment with progesterone (Boling, 

 Young and Dempsey, 1938). Although in 

 different proportions, the same combination 

 of hormones was later found necessary for 

 the stimulation of estrus in the rat (Boling 

 and Blandau, 1939; Beach, 1942a), mouse 

 (Ring, 1944), hamster (Frank and Fraps, 

 1945; Kent and Liberman, 1947), and cow 

 (Melampy, Emmerson, Rakes, Hanka and 

 Eness, 1957). Even in the rabbit, a species 

 in which the preovulatory swelling and 

 ovulation depend on the stimulation of coj)- 

 ulation, there is a brief period when an in- 

 jection of progesterone will heighten the 

 degree of estrus in an already moderately 



* For the estrogens, and possibly for proges- 

 terone, the manner of injection is important. In- 

 traperitoneal injections of an estrogen into fe- 

 male guinea pigs in amounts that are sufficient 

 when given subcutaneously are generally inef- 

 fective. When a divided dose of an estrogen given 

 subcutaneously was followed by an intravenous 

 injection of water-soluble estrone and sub- 

 cutaneously administered progesterone, the length 

 of heat was 15.7 hours compared with 9.3 hours 

 in the estrogen-conditioned animals injected only 

 with progesterone (Collins, Boling, Dempsey and 

 Young, 1938). Differences in the manner of in- 

 jection which are not always clear from the pub- 

 lished articles make comparison difficult. This 

 circumstance must be kept in mind in the re- 

 marks which follow. 



estrous animal (Sawyer and Everett, 1959). 

 In the four small mammals the amount of 

 estradiol benzoate necessary to condition 

 the animals for heat varies from 5 to 33 

 R.U., the amount of progesterone that will 

 bring such animals into heat is from 0.05 

 to 0.4 mg. (Table 19.1). In contrast to the 

 male which requires numerous daily injec- 

 tions for the restoration of normal mating 

 behavior, the female is brought into heat 

 by single injections of each hormone given 

 24 to 38 hours apart. 



When the response of the female guinea 

 l)ig to estrqgen and progesterone was being 

 studied it was clearly apparent that the 

 amounts of these substances sufficient to in- 

 duce a vigorous lordosis and mounting be- 

 havior were not stimulating normal estrous 

 vaginal changes and that the females would 

 not accept the males. It was later found that 

 stimulation of the vaginal changes char- 

 acteristic of heat in intact females required 

 treatment with larger quantities of estrogen 

 given over a period of 72 hours followed by 

 progesterone (Ford and Young, 1951). De- 

 ])ending on the animal, some adjustment of 

 the amounts of hormone and intervals may 

 be necessary, but when such a procedure 

 is employed spayed animals will accept the 

 male. Of especial interest for experimental 

 studies, is the demonstration by Larsson 

 (1957) that the sexual activity of the male 

 rat is not influenced by the way estrus is 

 induced in the female, i.e., whether it is by 



TABLE 19.1 



Amounts of estrogen and progesterone required for 

 the induction of sexual receptivity 



