Adaptation of Testosterone Production in Response to Low-Dose Effects of Nonylphenol

Nonylphenol (NP) is a non-ionic surfactant that is used widely as an industrial detergent. We have found that NP impairs male reproductive functions in vitro. However, the in vivo effects of NP on testosterone release at environmentally relevant doses remain unclear. Male rats were exposed to a low-dose of NP by oral gavage at 10 and 100 μg/kg body weight daily for 3-7 days. After 7 days of NP exposure, plasma testosterone level was significantly higher in higher NP exposure group than in the vehicle group. Higher basal testosterone release was found in the Leydig cells obtained from the rats treated with NP for 7 days. Additionally, evoked testosterone release was also higher after treating Leydig cells with human chorionicgonadotropin, 8-bromo-adenosine cyclic monophosphate, or forskolin. The expression of steroidogenic acute regulatory protein (StAR) was also increased by 40% in oral NP group. In contrast, the stimulatory effects were absent in Leydig cells treated with various steroid precursors. The stimulatory effects of NP were abolished after administration with intracellular calcium, EGFR and ERK blockers, which were well known to stimulate StAR activation. These results suggest that NP at an environmentally relevant dose could stimulate plasma testosterone level.