Estradiol-17 beta, insulin-like growth factor-I, and luteinizing hormone inhibit secretion of transforming growth factor beta by rat ovarian theca-interstitial cells

Theca cells have been shown to secrete transforming growth factor beta (TGF beta), but little is known regarding the regulation of thecal TGF beta secretion. To investigate the regulation of thecal TGF beta secretion and activation, rat theca-interstitial cells (TIC) isolated by Percoll gradient centrifugation were cultured with LH (0.01-10 ng/ml), androstenedione, androsterone, testosterone, or 5 alpha-dihydrotestosterone (DHT) (all 1 x 10(-9)-1 x 10(-5) M), estradiol (E2), estrone (both 1 x 10(-11)-1 x 10(-7) M), or IGF-I (30 ng/ml). Active TGF beta and total TGF beta in the conditioned medium were measured by bioassay. TIC spontaneously produced TGF beta, of which approximately 45% was in the active form. LH inhibited total TGF beta secretion (45% at 0.1 ng/ml of LH) and active TGF beta concentrations (40% at 0.3 ng/ml of LH). IGF-I inhibited active but not total TGF beta. Addition of LH did not cause any additional change in active or total TGF beta. Neither androstenedione, androsterone, testosterone, nor DHT had any effect on either active or total TGF beta secretion in the presence or absence of LH. In contrast, E2 inhibited both active (57%) and total (37%) TGF beta secretion. In the presence of LH, no additional effect of E2 was observed. ICI 182,780, a pure estrogen antagonist, reversed the E2 inhibition, suggesting that the E2 effect is mediated by estrogen receptors. We next investigated the role of E2 on TGF beta production by granulosa cells (GC).