Placental growth hormone (PGH) is secreted from the human placental syncytiotrophoblast into the maternal circulation. PGH levels in pregnant women correlate with the birth weight of their offspring. We hypothesized that metabolic regulators may alter PGH secretion. BeWo cells as human trophoblast models were treated for 24, 48, and 72 h with insulin, insulin-like growth factor (IGF)-1, cortisol, ghrelin, leptin and visfatin. Cyclic-adenosinmonophosphate treatment served as positive control. PGH concentrations in culture media were measured. Insulin reduced (p < 0.008; analysis of variance) PGH secretion from BeWo cells after 72 h. No effect was found when treating cells with IGF-1. Cortisol reduced PGH secretion after 48 h (p < 0.00118; analysis of variance) and 72 h (p < 0.015). Leptin and ghrelin both suppressed (p < 0.027 and p < 0.017, paired t test) whereas visfatin increased (p < 0.014, paired t test) PGH secretion at 72 h. Cyclic adenosinmonophosphate increased (p < 0.003) PGH secretion at 72 h. Our results indicate that in vitro PGH secretion by BeWo cells is regulated by hormonal factors and adipokines. We speculate on the existence of a maternal-placental regulatory loop, in which elevated insulin and leptin levels might down-regulate PGH secretion.