The cytologic localization and cellular levels of insulin receptors in the human ovary during follicular growth, regression and atresia were examined by the avidin/biotin immunoperoxidase techniques with a monoclonal antibody to insulin receptor. In primordial follicles, only the oocyte showed a weak immunostaining for insulin receptor, whereas the stromal cells surrounding primordial follicles were moderately immunostained. The earliest stage of follicular growth at which immunostaining for insulin receptor in granulosa cells and theca interna cells became apparent was the preantral stage. With the increase in the size of the follicles, the immunostaining of the oocyte and follicular elements intensified, whereas the staining intensity of the stromal cells surrounding growing follicles was reduced compared to those surrounding primordial follicles. The immunostaining in granulosa and theca interna cells persisted in the corpus luteum, and further intensified during the midluteal phase. In the regressing corpus luteum, the immunostaining was present only in the peripheral lutein cells adjacent to the central scar tissue. The corpus albicans was negative for the immunostaining, but the surrounding stromal cells exhibited predominant staining. In atretic follicles, the theca interna cells exhibited intense staining for insulin receptor without appreciable staining in the scattered granulosa cells, whereas the surrounding stromal cells were moderately immunostained.
This is the first study to demonstrate notable changes in insulin receptor expression in the oocyte, granulosa cells, theca cells, lutein cells and surrounding stromal cells during follicular growth, regression and atresia. The results obtained indicate insulin participation in oocyte maturation, follicular growth and stromal cell function. The increased expression of insulin receptors in theca interna cells of atretic follicles and in stromal cells surrounding the corpora albicans raises the intriguing possibility of insulin involvement in the transformation of theca interna cells into stromal cells. This implies that insulin may participate in remodelling ovarian local tissues following follicular atresia and luteolysis in the human ovary.