Neurotensin stimulates androgen production by theca cells in the monkey ovarian follicle

Androgen production by theca cells of the ovarian follicle is required for follicle growth and ovulation. Although theca steroidogenesis is known to be stimulated by luteinizing hormone (LH), the role of LH-stimulated paracrine mediators of ovulation such as neurotensin (NTS) has not been investigated. To explore the effect of NTS on ovarian theca steroidogenesis, monkey theca cells were treated with NTS or the LHCGR-ligand human chorionic gonadotropin (hCG). NTS increased theca production of the major theca androgen, androstenedione, as well as testosterone and dehydroepiandrosterone. Theca androgens were stimulated by hCG. Levels of progesterone, 17α-hydroxyprogesterone, and dehydroepiandrosterone were all stimulated by hCG. NTS decreased theca lipid droplet content but had no effect on theca LDL uptake or cholesterol quantity, while hCG did not affect theca cholesterol or lipids. NTS increased expression of CYP17A1 mRNA but not LDLR, STAR , CYP11A1 , or HSD3B , while hCG did not significantly impact any steroidogenic protein or enzyme mRNA examined. Altogether, NTS stimulates androgen production by monkey theca cells through increased utilization of stored lipids and upregulation of CYP17A1 expression. Increased dehydroepiandrosterone, in the absence of altered progesterone and 17α-hydroxyprogesterone, supports the concept that NTS stimulates androgen synthesis preferentially via the Δ 5 -steroidogenic pathway.