Insulin Receptor Expression in Follicular and Stromal Compartments of the Human Ovary over the Course of Follicular Growth, Regression and Atresia.

Abstract

Abstract. 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.

Stage-Limited Expression of myc Oncoprotein in the Human Ovary during Follicular Growth, Regression and Atresia.

“…Con- sequently, this suggests the intriguing possibility of myc expression involvement in the process of apoptosis during follicular atresia and/or the incorporation of surviving granulosa and theca cells from atretic follicles into the ovarian stroma to form interstitial tissue. Similar patterns of expression in the peripheral theca lutein cells of regressing corpora lutea and in the theca interna cells of atretic follicles as observed with myc oncoprotein have been shown with EGF receptor [16] and insulin receptor [27]. Immunohistochemical localization of myc oncoprotein in antral follicles.…”

Localization of binding sites for IGF-I, insulin and GH in the sow ovary

“…They were localized in stroma and in oocytes, granulosa and thecal cells (interna and externa) of preantral, small antral and large follicles and in luteal cells. Similarly, insulin receptors or corresponding mRNAs have been reported in human ovary in stroma, granulosa and theca cells and oocytes of growing follicles (Poretsky et al 1985, El-Roeiy et al 1993, Samoto et al 1993, as well as in rat and human luteal cells (Ladenheim et al 1984, Samoto et al 1993. In pigs, the presence of insulin receptors has been previously investigated only in granulosa cells and their presence has been detected (Rein & Schomberg 1982, Otani et al 1985.…”

“…In our study, atretic follicles also presented a clear labelling in granulosa and thecal cells. In women, insulin receptor mRNAs have been detected in pycnotic granulosa cells (El-Roeiy et al 1993), whereas no immunoreactivity for insulin receptor has been revealed in atretic follicles (Samoto et al 1993). The presence of insulin receptor in granulosa and theca interna of atretic and healthy follicles, as well as in corpora lutea of both stages, may suggest that this receptor is constitutively expressed in pigs.…”

Effects of IGF-I bioavailability on bovine preantral follicular development in vitro

“…It should also be noted that high concentrations of IGF-I, as well as acting via specific IGF receptors, can also bind to insulin receptors within the follicle (Giudice 1992). Insulin receptors have been detected in oocytes, granulosa, and theca cells of human preantral follicles ( Samoto et al 1993), and also in bovine follicles (Armstrong et al 2001). Therefore, this would provide a further mechanism, in addition to lack of regulation by binding proteins, for over-stimulation of the oocyte in the presence of the highest concentration of recombinant IGF-I.…”