Intratesticular Ovarian Grafts and the Problem of Tumorigenic Hypophysial Imbalances Due to Autolytic Compounds

INTRATESTICULAR OVARIAN GRAFTS AND THE PROBLEM OF TUMORIGENIC HYPOPHYSIAL IMBALANCES DUE TO AUTOLYTIC COMPOUNDS ALEXANDER LIPSCHUTZ and VERA I. PANASEVICH* Introduction There is now no doubt as to the justification of the original idea of Biskind [1,2] that a functional hypophysial imbalance is responsible for tumors originating in castrated animals in intrasplenic ovarian grafts, the latter being unable to control the gonadotrophic function of the hypophysis. The doubts of Guthrie [3] as to an hypophysial imbalance being responsible for these intrasplenic tumors, doubts based on the statement of FeIs [4] that tumors may originate in ovarian grafts in other sites of the body, are now fully invalidated. In collaboration with Cerisola, Panasevich, and others, we have shown that ovarian tumors in intrarenal and intrahepatic ovarian grafts are different from the tumors in intrasplenic grafts: the intrarenal or intrahepatic growths are microtumors with luteomas predominating , compared with the macrotumors with granulosa-cell tumors predominating in intrasplenic grafts; and when intrasplenic transplantation of ovary is "combined" in the same animal with intrarenal transplantation, the intrasplenic tumors are similar to the intrarenal microtumors [5-10]. Our conclusion was that the differential evolution of ovarian tumors according to the site of the graft is dependent on differential degrees of hypophysial imbalances. The results as obtained in "combined " grafts, both grafts offering no more than microtumors, are by no means due to the "amount" of ovary grafted in these experiments . There is the fact that two intrasplenic macrotumors may originate when grafting the two ovaries, or two halves of an ovary, into the spleen [H]. On the other hand, quite new fundamental problems as to tumori- * Address: Section of Experimental Pathology, Institute of Neurosurgery, Universidad de Chile and National Health Service, Santiago de Chile. 22 I Alexander Lipschutz and Vera I. Panasevich · Intratesticular Ovarian Grafts genesis in ovarian grafts originated with the discovery by Gardner [12, 13] that tumors appear also in ovaries grafted into the testicle of both unilaterally castrated and normal mice.1 The last-mentioned fact can be taken as an important hint that the hormonal events responsible for experimental ovarian tumorigenesis in males and females are not the same: tumorigenesis in intrasplenic ovarian grafts does not take place when the second ovary has been left intact in the body [2]. Another definite hint as to the existence of various factors which might be responsible for ovarian tumorigenesis is given by the fact that the behavior of an ovary grafted into the male can be influenced by experimentally induced testicular changes. Thus, the taking of an ovarian graft in the kidney of the male guinea pig is facilitated, and follicular development is accelerated, by various operative interferences on the testicle, for instance, resection of the epididymis [20, 21] or experimental cryptorchidism even when only unilateral [22, 23]. Thus, the question arose of whether abnormal autolytic substances produced in degenerating seminiferous tubules may influence the behavior of the ovarian graft [24, 25]. Takewaki [26] corroborated our findings and subsequently gave evidence that cryptorchidism in rats also favors the evolution of the ovary grafted into the spleen [27]. One will suppose that the hypothetical autolytic substances produced in the degenerating seminiferous tubules are active by the intermediation of the hypophysis. Of fundamental interest here is the work of Ely [28]. He administered an "antigonadotrophic serum (produced in rabbits against sheep pituitary extract)" to castrated female mice with intrasplenic ovarian grafts. No ovarian tumors appeared in these animals. After all this, we took the decision to study the behavior of the ovary grafted into the testicle in various experimental conditions in mice. The Comparative Behavior of the Ovary Grafted into the Testicle of Unilaterally Castrated and Intact Mice Animals of BALB-A were operated on at the age of two months. After the ovary was introduced into the testicle, the latter was ? Sand [14, 15] was the first to graft the ovary into the testicle, in his studies on the endocrine action of the genital glands. Later on, Sand's method was made use of in our laboratory [16-19]. This work was done on rats and guinea pigs. However, all these experiments were of short duration and did not allow tumoral growth. Perspectives...