Neurotensin: A Neuropeptide induced by hCG in the Human and Rat Ovary during the Periovulatory Period

Neurotensin (NTS) is a tridecapeptide that was first characterized as a neurotransmitter in neuronal cells. The present study examined ovarian NTS expression across the periovulatory period in the human and the rat. Women were recruited into this study and monitored by transvaginal ultrasound. The dominant follicle was surgically excised prior to the LH surge (preovulatory phase) or women were given 250 μg hCG and dominant follicles collected 12-18 h after hCG (early ovulatory), 18-34 h (late ovulatory) and 44-70 h (postovulatory). NTS mRNA was massively induced during the early and late ovulatory stage in granulosa cells (15,000 fold) and theca cells (700 fold). In the rat, hCG also induced Nts mRNA expression in intact ovaries and isolated granulosa cells. In cultured granulosa-lutein cells (GLC) from IVF patients, NTS expression was induced 6 h after hCG treatment whereas in cultured rat granulosa cells NTS increased 4 h after hCG treatment. Cells treated with hCG signaling pathway inhibitors revealed that NTS expression is partially regulated in the human and rat GC by the epidermal-like growth factor (EGF) pathway. Human GLC and rat granulosa cells also showed that Nts was regulated by the PKA pathway along with input from the PI3K and MAPK pathways. The predominate NTS receptor present in human and rat granulosa cells was SORT1, whereas NTSR1 and NTSR2 expression was very low. Based on NTS actions in other systems, we speculate that NTS may regulate crucial aspects of ovulation such as vascular permeability, inflammation, and cell migration.