Sex-linked histoincompatibility of pituitary isografts in the C57BL strain of mice.

Abstract

AbstractTwo pituitary glands were isografted, one on each side, into the fourth mammary gland fat pads of intact virgin female mice aged 3 to 6 months; C57BL hosts received grafts from either male or female sibling donors of the same age, and BALB/c hosts from males only. The success or failure of the grafts was determined in three ways: 1) vaginal smears as a clinical criterion, 2) gross observation of the transplantation site under anesthesia, and 3) histological examinations of the pituitary grafts. The rates of successful pituitary isografts were shown to be: in C57BL hosts, 13/46 (28.3%) from male donors and 20/20 (100%) from female donors; in BALB/c hosts, 38/38 (100%) from male donors. In both C57BL and BALB/c hosts, daily vaginal smear charts showed a pseudopregnancy‐like pattern when pituitary isografts were accepted. However, when the C57BL hosts rejected the grafts, such hosts returned to their apparently normal vaginal cycles after a certain period of prolonged diestrus immediately following transplantation. The occurrence of full estrous smears in the C57BL hosts which rejected pituitary grafts was significantly greater than that observed in the hosts maintaining their grafts. From 90 to 200 days following the pituitary isografts, thirty hosts which had rejected their grafts received a second set of two pituitary isografts from male donors in the same manner as the primary set. Only four out of thirty hosts (13.3%) accepted the second pair of pituitary grafts. Moreover, the second‐set pituitary isografts were rejected almost immediately. The mammary glands of all hosts in which pituitary isografts survived showed varying degrees of development, according to the duration of grafts before autopsy.The results in the present experiments are in accordance with those originally reported by Eichwald and Silmser (1955) concerning skin grafting. As postulated by Hauschka (1955) and Snell (1956), rejection of tissues isografted from male donors to female hosts may be due to a sex‐linked histocompatibility gene on the Y chromosome. Eichwald et al. (1957, 1958) observed a faster rejection of second‐set skin grafts than of first‐set grafts. Similar results were obtained in the present experiments following the second‐set pituitary isografts. The fact that some female hosts were able to accept pituitary isografts from male C57BL donors would indicate that the histoincompatibility antigen is relatively weak in the pituitary tissue of male C57BL mice. The reasons for the difficulty of induction of mammary cancer in the C57BL strain of mice by pituitary isografts are obscure. The lack of adequate hormonal stimulation in the C57BL female hosts which have rejected pituitary isografts received from male donors may possibly be one of the most crucial factors in the failure to develop mammary cancer. It seems possible to explain the general failure of induction of mammary cancer by pituitary isografts in C57BL mice by introducing the new concept of sex‐linked histoincompatibility of pituitary isografts in this strain.