GESTATION 



973 



reported the production of approximately 

 250 mg. progesterone into the peripheral 

 circulation every 24 hours. This and other 

 evidence tends to prove that the placenta 

 is the major source of progesterone in the 

 human species. However, with respect to 

 other species, progesterone has been found 

 only in the placenta of the mare (Short, 

 1957) although in amounts much less than 

 in the human being. Placentas of the cow, 

 ewe, sow, or bitch were all negative. Al- 

 though the placenta of the mare contains 

 progesterone and castration does not lead 

 to abortion after day 200 of gestation, no 

 progesterone was found in the peripheral 

 blood or uterine vein blood. The ewe offers 

 an even more intriguing problem inasmuch 

 as (1) a discrepancy exists between the 

 biologic and chemical values for progester- 

 one in the peripheral blood, (2) the pla- 

 centas contain no progesterone, and (3) no 

 {progesterone is found in the uterine vein 

 blood (Edgar, 1953). This has led to the 

 conclusion that the maintenance of preg- 

 nancy in the ewe may be dependent on an 

 extra-ovarian, extraplacental source of pro- 

 gesterone. 



If such a conclusion is correct, and it 

 must be added that the evidence is still 

 tenuous, then the adrenal cortex must be 

 considered as a possible source. Beall and 

 Reichstein isolated a small amount of pro- 

 gesterone from the adrenal cortex in 1938 

 and Heehter, Zaffaroni, Jacobson, Levy, 

 Jeanloz, Schenker and Pincus (1951) dem- 

 onstrated from perfusion experiments that 

 progesterone is an important intermediate 

 metabolite in the synthesis of the adrenal 

 corticoids. In addition, it has long been 

 known that desoxycorticosterone possesses 

 progesterone-like activity (Courrier, 1940) 

 which is due to a conversion of the desoxy- 

 corticosterone molecule to a gestagen. This 

 has been shown by experiments in vivo in 

 the monkey (Zarrow, Hisaw and Bryans, 

 1950), rat, and rabbit (Lazo-Wasem and 

 Zarrow, 1955), and by an incubation experi- 

 ment with rat tissue (Lazo-Wasem and 

 Zarrow, 1955). In addition, Zarrow and 

 Lazo-Wasem reported the release of a ges- 

 tagen from the adrenal cortex of the rat 

 and rabbit following treatment with 

 ACTH. The substance was obtained from 

 the peripheral blood and measured by the 



Hooker-Forbes test, but it was not identi- 

 fied chemically. This was followed by the 

 finding that pregnanediol is present in the 

 urine of ovariectomized women, but not 

 ovariectomized, adrenalectomized women 

 (Klopper, Strong and Cook, 1957), and by 

 the finding that progesterone is present in 

 the adrenal venous blood of the cow, sow, 

 and ewe (Balfour, Comline and Short, 

 1957). In all instances the concentration 

 of progesterone in the adrenal venous blood 

 was 10 to 100 times greater than the con- 

 centration in the arterial blood. Thus the 

 total evidence that the adrenal cortex can 

 secrete progesterone is more than adequate. 

 The question remains as to whether the 

 adrenal cortex contributes to the proges- 

 terone pool of the body during pregnancy 

 and whether a species difference exists here. 



D. RELAXIN 



The initial discovery by Hisaw (1926, 

 1929) of the presence of an active substance 

 in the blood and ovaries responsible for 

 relaxation of the pubic symphysis of the 

 guinea pig has led in recent years to a con- 

 sideration of this substance as a hormone 

 of pregnancy (Hisaw and Zarrow, 1951). 

 Some doubt as to the existence of relaxin 

 was raised in the 1930's by investigators 

 who were able to show that pubic relaxa- 

 tion in the guinea pig could be obtained 

 with estrogen alone or estrogen and pro- 

 gesterone (de Fremery, Kober and Tausk, 

 1931; Courrier, 1931; Tapfer and Hasl- 

 hofer, 1935; Dessau, 1935; Haterius and 

 Fugo, 1939). This matter was resolved by 

 the demonstration that pubic relaxation in 

 the guinea pig following treatment with the 

 steroids or relaxin differed in ( 1 ) time re- 

 quired for relaxation to occur, (2) histo- 

 logic changes in the pubic ligament, and (3) 

 treatment with estrogen and progesterone 

 which induced the formation of relaxin 

 (Zarrow, 1948; Talmage, 1947a, 1947b). 

 Subsequent discoveries of additional bio- 

 logic activities possessed by relaxin and fur- 

 ther purification of the hormone has led to 

 the conclusion that relaxin is an active sub- 

 stance in the body, and that it plays a sig- 

 nificant role during parturition. The hor- 

 mone has been found in the blood or other 

 tissues of the dog, cat, rabbit, sheep, cow, 

 rat, and man. The specific action of this 



