Kit ligand actions on ovarian stromal cells: Effects on theca cell recruitment and steroid production

Abstract

Factors that control recruitment of theca cells from ovarian stromal‐interstitial cells are important for early follicle development in the ovary. During recruitment, theca cells organize into distinct layers around early developing follicles and establish essential cell–cell interactions with granulosa cells. Recruitment of theca cells from ovarian stromal stem cells is proposed to involve cellular proliferation, as well as induction of theca cell‐specific functional markers. Previously, the speculation was made that a granulosa cell‐derived “theca cell organizer” is involved in theca cell recruitment. Granulosa cells have been shown to produce kit‐ligand/stem cell factor (KL). KL is known to promote stem cell proliferation and differentiation in a number of tissues. Therefore, the hypothesis was tested in the current study that granulosa cell‐derived KL may help recruit theca cells from undifferentiated stromal stem cells during early follicle development. The actions of KL were examined using adult bovine ovarian fragment organ culture and isolated ovarian stromal‐interstitial cells. In organ culture KL significantly increased the number of theca cell layers around primary follicles. Experiments using purified stromal‐interstitial cell cultures showed that KL stimulated ovarian stromal cell proliferation in a dose‐dependent manner. Stromal cell differentiation into theca cells was analyzed by the induction of theca cell functional markers (i.e., androstenedione and progesterone production). Bovine ovarian stromal cells produced low levels of androstenedione (5–40 ng/μg DNA) and progesterone (5–30 ng/μg DNA) in vitro that were approximately 20‐fold lower than theca cells under similar conditions. Treatment with KL did not affect ovarian stromal cell androstenedione or progesterone production. Interestingly, hormones such as estrogen and hCG did stimulate stromal cell steroid production. The results in this study suggest that granulosa cell‐derived KL appears to promote the formation of theca cell layers around small (i.e., primary) ovarian follicles. KL directly stimulated ovarian stromal cell proliferation but alone did not induce functional differentiation (i.e., high steroid production). Therefore, KL is proposed to promote early follicle development by inducing proliferation and organization of stromal stem cells around small follicles. Observations suggest that KL may act as a granulosa‐derived “theca cell organizer” to promote stem cell recruitment of ovarian stromal cells in a manner similar to the way that KL promotes hematopoietic and lymphoid stem cells in bone marrow and the thymus. Mol. Reprod. Dev. 55:55–64, 2000. © 2000 Wiley‐Liss, Inc.

KIT receptor-positive cells in the bovine corpus luteum are primarily theca-derived small luteal cells

“…According to other groups, thecal cells of antral follicles express both KITC mRNA and KIT protein (Motro & Bernstein 1993, Parrott & Skinner 1997, Driancourt et al 2000, Brankin et al 2004. Obviously, the KIT expression persists after ovulation in the theca-derived capsule/septum in (Parrott & Skinner 2000). Apart from vascular cells, the thecal layer consists of steroidogenic cells and fibroblasts, both of which are candidate cells for the small KITC cells in the bovine CL.…”

“…Small luteal cells are likely candidates, because they are known to be derived from the theca where KIT transcription takes place (Driancourt et al 2000). In addition, isolated thecal cells secrete an increased amount of progesterone under KIT stimulation when compared with unstimulated controls (Parrott & Skinner 2000).…”

Actions of anti-Müllerian hormone on the ovarian transcriptome to inhibit primordial to primary follicle transition

“…KITL receptors (c-kit) are present on oocytes and theca cells (Horie et al 1991, Manova et al 1993, Motro & Bernstein 1993. KITL acts to recruit thecal cells from surrounding ovarian stroma during the primordial to primary follicle transition (Parrott & Skinner 2000). How KITL interacts with AMH to regulate primordial to primary follicle transition is also examined in the current study.…”

Immunization with ovarian autoantigens leads to reduced fertility in mice following follicular dysfunction

“…Also, the preantral to antral transition is most susceptible to follicular atresia. Several oocyte-and theca cell-derived factors promote granulosa cell proliferation and suppress apoptosis of granulosa cells, thereby preventing follicular atresia (Parrott & Skinner 2000, Orisaka et al 2009). It has been demonstrated that Effect of ovarian antibodies on mouse fertility oocyte-theca cell interaction also has a major role in folliculogenesis including activation of resting follicles, early growth, as well as terminal differentiation (Vanderhyden et al 1990, 1992, Eppig et al 2002, Matzuk et al 2002.…”