Site of Production of Oestrogen in Rat Ovary as Studied in Micro‐Transplants

Abstract

SUMMARY The present paper is concerned with an investigation on the site of production of oestrogen in the rat ovary by a method designed to yield more direct evidence than hitherto available. A dissection technique was devised permitting isolation of small cell aggregates from the rat ovary containing only one endocrine cell system. Such cell systems alone or in certain combinations were auto‐transplanted to the anterior chamber of the eye of spayed animals, a contiguous vaginal autotransplant serving as an indicator of the oestrogenic activity of the ovarian grafts. The specificity of this indicator system to oestrogen is discussed. As to the ovarian grafts, only in exceptional cases did they produce systemic hormonal effects, and interference by oestrogenic substances from other sources or by metabolites from steroids released in the grafts was excluded by the appearance of the vagina in situ and a control vaginal transplant in the other eye. The following isolated cell systems were transplanted: interstitial cells, theca interna cells, corpus luteum cells and granulosa cells. All of these cell types were able to survive when grafted. In spite of the complex topography of the rat ovary, it proved possible to secure a certain number of grafts consisting of interstitial cells only or of theca interna cells only. Uncontaminated grafts of granulosa cells and corpus luteum cells could be readily obtained. The dissection technique thus provides a tool for studying ovarian tumours experimentally induced in grafts originally containing only one type of endocrine cells. The transplanted granulosa cells were luteinised and formed cell aggregates of the same histological structure as the normal corpus luteum. The following combinations of cell systems were studied: interstitial cells + corpus luteum cells and theca interna cells + granulosa cells or corpus luteum cells. Secretion of oestrogen was never recorded in transplants of the pure cell systems but only in transplants containing theca interna cells or interstitial cells combined with granulosa cells or corpus luteum cells. The validity of these results is discussed and it is excluded that errors in the experimental method might have caused the negative results with the isolated cell systems. Isolated follicles were not transplanted, but the material permitted an indirect analysis of the oestrogen‐producing capacity of follicles in different developmental stages, showing that this probably arises with the development of the theca interna gland cells. It was found that a single follicle with few theca interna cells could produce a local oestrogenic effect on the indicator epithelium, while a single follicle of preovulatory size and well‐developed thecal gland was able to produce full oestrous reaction of the vagina and uterus in situ . It is concluded from these results that the production of oestrogen is dependant on an interplay between theca interna gland cells or interstitial cells and corpus luteum cells or granulosa cells. The primary source of oestrogen in the ovary is discussed against the background of the literature and the present findings. It is concluded that the theca interna gland cells and the interstitial gland cells most probably constitute the oestrogen‐producing system in the ovary but that these cells are functionally dependent on the system granulosa‐corpus luteum cells. The possibility of intra‐ovarian mechanisms operating in both directions between the two principal cell‐systems — the oestrogen‐ and the progestin‐producing — is discussed.