An Involvement of Estrogen Receptors in the Transcriptional and Translational Induction of Growth Hormone Evoked by Xenoestrogens in Rat Pituitary Gland.

Growth hormone (GH) plays a pivotal role in the regulation of growth, development and body composition. In the previous study, we demonstrated that in vitro exposure to estrogenic endocrine disruptors (EDs) resulted in an increase in GH expression through estrogen receptor (ER) dependent pathways, suggesting that ER appears to be involved in both EDs-induced GH gene transcription and GH secretion in rat pituitary GH3 cells. In order to provide a new insight into in vivo estrogenic ED effects in the GH expression, an immature rat model was employed to determine the potential role of ERs in ED-induced GH expression in rat pituitary gland. At postnatal day 14, immature rats were treated with 4-tert-octyl-phenol (OP), p-nonylphenol (NP) and bisphenol A (BPA) in a dose-dependent manner, the expression levels of GH mRNA and protein were analyzed by a real-time quantitative PCR and Western blot/immunohistochemistry (IHC), respectively. An anti-estrogen, ICI 182,780, was used to examine the potential involvement of ERs in the induction of GH by EDs during critical windows of development. Treatment with a high dose (600 mg/kg body weight [BW]) of OP or NP significantly increased GH mRNA expression at 48 h. OP and NP-induced increase in GH mRNA was completely reversed by co-treatment with ICI 182,780. However, no significant difference was observed by treatment with BPA or co-treatment with an anti-estrogen at the transcriptional levels. Interestingly, exposure to these EDs at a high dose (600 mg/kg BW) markedly enhanced GH protein level in rat pituitary gland, whereas pre-treatment with ICI 182,780 significantly attenuated EDs-induced GH protein. Taken together, we demonstrated for the first time that in vivo exposure to OP, NP or BPA resulted in an increase in GH mRNA and protein levels in rat pituitary gland and the mode of these actions may be involved in an ER-mediated signaling pathway. Thus these results may provide critical evidence in EDs-induced dysregulation of pituitary GH expression and be very important to elucidate the potential impacts of EDs in altered body growth and development as predict the health risk from EDs-exposure to humans and wildlife.