1010 



SPERM, OVA, AND PREGNANCY 



ently by estradiol (prolonged treatment) or 

 relaxin (single injection). It is also possible 

 to conclude that the action of progesterone 

 is indirect and due to the formation of re- 

 laxin in the uterus (Zarrow, 1948; Hisaw, 

 Zarrow, Money, Talmage and Abramovitz, 

 1944) . In the mouse, however, progesterone 

 inhibits the action of relaxin on the pubic 

 symphysis (Hall, 1949). 



Further evidence that two hormones are 

 involved in pubic relaxation was provided 

 by histologic examination of the pubic liga- 

 ment. Symphyseal relaxation following es- 

 trogen appeared to be due to a resorption of 

 bone and a proliferation of loose fibrous 

 connective tissue with an increase in mucoid 

 alkaline phosphatase and water content 

 (Talmage, 1947a, 1947b, 1950; Heringa and 

 van der Meer, 1948). Relaxin produced a 

 breakdown and splitting of the collagenous 

 fibers into thin threads and a similar change 

 was noted with progesterone (Talmage, 

 1947a, 1950). 



Histochemical and biocliemical studies of 

 the pubic symphysis have recently been re- 

 viewed (Frieden and Hisaw, 1933) and tend 

 to show that relaxin produces specific 

 changes. These include loss of metachro- 

 masia (Heringa and van der Meer, 1948) , 

 accumulation of Evans blue m vivo, and in- 

 creased solubility of the glycoproteins in 

 the McManus-Hotchkiss reaction, all of 

 wiiich indicate that a depolymerization of 

 the ground substance and basement mem- 

 brane glycoproteins had occurred (Perl and 

 Catchpole, 1950) . Frieden and Hisaw (1951) 

 found an increase in water content of the 

 symphyseal tissue, but failed to find a de- 

 crease in the water-soluble hexose and hex- 

 oseamine following a single injection of re- 

 laxin. On the basis of a depolymerization 

 of ground substance, a decrease should have 

 occurred. However, repeated injections of 

 relaxin led to a decrease in the insoluble 

 hexoses and hexoseamines. In addition, con- 

 sistent decreases in collagen content and 

 trypsin-resistant protein content were noted. 

 No hyaluronidase was found, but ^-glucu- 

 ronidase was increased during relaxation. 

 Gersh and Catchpole (1949) reported the 

 presence of a collagenase from histochemi- 

 cal studies, but no confirmation has been 

 forthcoming. Relaxin also has a protein 



anabolic effect which occurs in the absence 

 of pubic relaxation (Frieden, 1956). This 

 action was demonstrated by the increased 

 up-take of labeled glycine by the connective 

 tissue proteins of the pubic symphysis. Re- 

 cent experiments indicate that relaxin not 

 only acts in conjunction with the female 

 sex steroids but can also act alone (Bren- 

 nan and Zarrow, 1959). However, it is ap- 

 parent that the available data are still in- 

 adequate for a clear understanding of the 

 mechanism of action of relaxin. 



Relaxation of the pubic symphysis of the 

 mouse has been studied in great detail by 

 Hall. In a series of reports she showed that 

 pubic relaxation occurs in the mouse dur- 

 ing pregnancy and following treatment with 

 estradiol and relaxin (Hall and Newton, 

 1946a, b). This was later confirmed by Kli- 

 man, Salhanick and Zarrow (1953). Con- 

 trary to the results reported following work 

 on the guinea pig, progesterone not only 

 failed to influence the effect of estrone on 

 the pubic symphysis of the mouse, but pro- 

 gesterone also inhibited the action of re- 

 laxin. It was suggested that this inhibition 

 is the result of an antagonism by progester- 

 one on the action of relaxin and that a true 

 species difference exists (Hall, 1949, 1955). 

 Histologic studies revealed that changes in 

 the pubic symphysis during pregnancy and 

 after treatment with relaxin and estradiol 

 are similar (Hall, 1947) . These changes con- 

 sist of proliferation of articular hyaline car- 

 tilage, resorption of the medial ends of the 

 pubes, lengthening of the pubic ligament by 

 formation of new cartilage, and reversion of 

 the cartilage to collagenous connective tis- 

 sue. Hall (1956) suggested that estradiol 

 causes a depolymerization of the mucopoly- 

 saccharides through enzymatic action re- 

 sulting in a matrix sufficiently pliable to 

 respond to the tensions set up by relaxin. 

 Evidence presented in support of this con- 

 cept was the loss of metachromasia and the 

 increase in water. In addition, a two-step 

 effect was seen with relaxin: (1) complete 

 degradation of the matrix, and (2) the ap- 

 pearance of a gap in the cranial part of the 

 cartilage produced by stretching of the sym- 

 physeal cleft. Some data in support of the 

 latter part of this concept were presented by 

 van der Meer (1954) who showed that in- 



