ESTROGEN AND PROGESTERONE 



577 



nounced swelling during the follicular phase 

 of the cycle. A maximal size is attained by 

 the middle of the cycle followed by a rapid 

 regression and loss of edema which at least 

 in the baboon is associated with a marked 

 increase in the output of urine (Gillman, 

 1937a; Krohn and Zuckerman, 1937). The 

 subsidence of the sexual skin begins approxi- 

 mately at the time of ovulation and remains 

 in the reduced condition throughout the 

 luteal phase, followed by a subsequent ini- 

 tiation of swelling during or soon after 

 menstruation (Zuckerman, 1930, 1937e; 

 Zuckerman and Parkes, 1932; Gillman and 

 Gilbert, 1946; Young and Yerkes, 1943; 

 Nissen and Yerkes, 1943). 



A w^ell developed sexual skin is present 

 in the monkey {Macaca mulatta) only dur- 

 ing adolescence. With the appearance of 

 the menstrual cycles the sexual skin under- 

 goes a process of maturation into the adult 

 condition in which cyclic changes in edema 

 are absent and the most noticeable feature 

 is a vivid red color. Such coloration is due 

 to vascular engorgement rather than pig- 

 ment (Collings, 1926) and involves the 

 perineum, the buttocks, and may extend for 

 various distances down the legs and over 

 the symphysis pubis. The development and 

 maturation of the sexual skin have been de- 

 scribed in considerable detail by several in- 

 vestigators (Hartman, 1932; Zuckerman, 

 van Wagenen and Gardiner, 1938) . 



The sexual skin has been of considerable 

 interest both as to the nature of its re- 

 sponsiveness to ovarian hormones and the 

 manner in which its grossly visible changes 

 during the menstrual cycle parallel events 

 occurring in the reproductive tract. The 

 sudden loss of edema at the conclusion of 

 the follicular phase not only signals ovula- 

 tion but also raises the question as to 

 whether the loss of tissue fluid is due to a 

 decrease in estrogen or is the direct effect 

 of progesterone. The importance of this 

 becomes obvious when it is considered that 

 a similar process also goes on simultaneously 

 in the endometrium and raises the question 

 again as to the respective roles played by 

 estrogen and progesterone in endometrial 

 growth and menstruation. 



That the development and edema of the 

 sexual skin of adolescent rhesus monkeys 

 depend on the ovaries was first demon- 



strated by Allen ( 1927 ) . Involution and loss 

 of color follow castration, and the normal 

 condition can be restored by the injection 

 of estrogen. Also, when estrogen treatment 

 is continued for several weeks maturation of 

 the sexual skin occurs and a condition char- 

 acteristic of that in the adult is established 

 (Zuckerman, van Wagenen and Gardiner, 

 1938). The genital area loses its edema and 

 develops a brilliant red color which is re- 

 tained as long as estrogen is administered. 

 Once this mature condition is established 

 the response of the sexual skin to subse- 

 quent estrogen treatments is limited to a 

 change in color. 



Similar experiments have been performed 

 on the chacma baboon, Papio porcarius 

 (Parkes and Zuckerman, 1931; Gillman, 

 1937b, 1938, 1940a). The large sexual skin 

 of these animals is very responsive to es- 

 trogen and development equal to that of the 

 follicular phase of the menstrual cycle can 

 be readily induced by daily injections for 

 about 2 weeks. However, the perineal swell- 

 ing of the baboon differs from the sexual 

 skin of the genital area of the rhesus mon- 

 key in that it does not "mature" under the 

 influence of estrogen. 



When large doses of estrogen are given to 

 a rhesus monkey a generalized edema of 

 the skin occurs beyond the genital area. 

 This first appears as deeply indented swell- 

 ings along the sartorii from groin to knee, 

 and next appears at the base of the tail and 

 spreads gradually upward until it involves 

 the entire dorsal portion of the trunk. At the 

 same time, the skin of the face, scalp, and 

 supraorbital ridges becomes swollen and 

 finally the edema may extend out on the 

 arms and down the legs to the ankles (Bach- 

 man, Collip and Selye, 1935; Hartman, 

 Geschickter and Speert, 1941). A daily 

 dose of 500 /xg. or more of estriol or estradiol 

 w^ll produce this condition within 2 to 3 

 weeks and, when the treatment is con- 

 tinued for an extended period the effect 

 tends to subside. 



Progesterone has a strong inhibitory ac- 

 tion on the effects produced by estrogen on 

 both the genital and extragenital sexual 

 skin of the monkey. If daily injections of 

 progesterone are added to the treatmeiu 

 after full development of the sexual skin 

 has been induced by estrogen, there is a 



