Estrogen Receptors are Involved in Xenoestrogen Induction of Growth Hormone in the Rat Pituitary Gland

Abstract

Growth hormone (GH) plays a pivotal role in the regulation of growth, development and body composition. In order to provide new insights into estrogenic endocrine disruptor (ED) activities in the pituitary gland and the potential role played by estrogen receptors (ERs) in mediating their effects in vivo, we examined GH expression in the pituitary gland of an immature rat model. At postnatal day 14, immature rats were treated with various doses of 4-tert-octylphenol (OP), p-nonylphenol (NP) and bisphenol A (BPA), and the GH mRNA and protein expression levels were analyzed by real-time quantitative PCR and western blot/immunohistochemistry (IHC), respectively. An anti-estrogen (ICI 182780) was used to examine the potential involvement of ERs in ED-induced GH expression during critical windows of development. GH mRNA expression increased significantly 48 h after treatment with a high dose (600 mg/kg body weight [BW]) of OP or NP. However, this induction was abolished completely by co-treatment with ICI 182780. No significant difference in GH mRNA expression was observed following treatment with BPA or co-treatment of BPA with the anti-estrogen. Exposure to high doses (600 mg/kg BW) of these EDs significantly enhanced GH protein expression in the rat pituitary gland, whereas pretreatment with ICI 182780 markedly reduced this expression. Taken together, we have demonstrated for the first time that in vivo exposure to EDs can induce GH mRNA and protein expression in the rat pituitary gland and that their activities may involve an ER-mediated signaling pathway. These results may provide critical evidence for ED-induced dysregulation of pituitary GH expression and thus may be important for elucidating the potential impacts of EDs in altered body growth and development and for predicting the health risks of ED exposure in humans and wildlife.