Growth factor betacellulin can stimulate human granulosa cell functions and promote gonadotropin actions

BACKGROUND: Betacellulin (BTC), an EGF-family growth factor expressed in granulosa cells, is implicated in ovarian regulation; however, its interactions with gonadotropins in humans remain unclear. OBJECTIVE: To determine how BTC alone or combined with follicle-stimulating hormone (FSH) or luteinizing hormone (LH) affects human granulosa cell viability, proliferation, apoptosis, and progesterone secretion. METHODS: Human granulosa cells were treated with BTC (1-100 ng/ml) ± FSH or LH (100 ng/ml). Viability was measured by Trypan blue exclusion; proliferation and apoptosis by immunocytochemistry; and progesterone by ELISA. RESULTS: BTC dose-dependently increased viability, proliferation (cyclin B1, PCNA), and progesterone secretion, while reducing apoptosis (bax, caspase-3). Both FSH and LH enhanced all BTC effects, further increasing proliferation, viability, progesterone output, and anti-apoptotic activity. CONCLUSION: BTC may regulate human granulosa cell function, acting in concert with gonadotropins to modulate viability, proliferation, apoptosis, and steroidogenesis, highlighting its role as a paracrine mediator in ovarian physiology.