Environmental estrogens inhibit the expression of insulin-like growth factor mRNAs in rainbow trout in vitro by altering activation of the JAK-STAT, AKT-PI3K, and ERK signaling pathways

Andrea M. Hanson, Jeffrey D. Kittilson, Mark A. Sheridan

Research output: Contribution to journalArticlepeer-review

Abstract

Environmental estrogens (EE) have been found to disrupt a host of developmental, reproductive, metabolic, and osmoregulatory process in a wide-range of animals, particularly those in aquatic ecosystems where such compounds concentrate. Previously, we showed that EE inhibited post-embryonic organismal growth of rainbow trout in vivo, but the precise mechanism(s) through which EE exert their growth inhibiting effects remain unknown. In this study, we used rainbow trout (Oncorhynchus mykiss) as a model to investigate the direct effects of 17β-estradiol (E2), β-sitosterol (βS), and 4-n-nonylphenol (NP) on the synthesis of insulin-like growth factors (IGFs) and to elucidate the mechanism(s) by which EEs exert such effects. E2, βS, and NP significantly inhibited the expression of both IGF-1 and IGF-2 mRNAs in liver and gill in a time- and concentration-related manner. Although the response evoked by each EEs on the expression of IGF mRNAs was similar, the potency and efficacy varied with EE; the rank order potency/efficacy was as follows: E2 > NP > βS. The effects of EEs on the expression of IGF mRNAs was blocked by the estrogen receptor (ER) antagonist, ICI 182780. The mechanism(s) through which EEs inhibit IGF mRNA expression were investigated in isolated liver cells in vitro. EE treatment deactivated JAK, STAT, ERK, and AKT. Moreover, blockade of growth hormone (GH)-stimulated IGF expression by EE was accompanied by deactivation of JAK, STAT, ERK, and AKT. EEs also increased the expression of suppressor of cytokine signaling 2 (SOCS-2), a known inhibitor of JAK-2–an action that also was blocked by ICI 182780. These results indicate that EEs directly inhibit the expression of IGF mRNAs by disrupting GH post-receptor signaling pathways (e.g., JAK, STAT, ERK, and AKT) in an ER-dependent manner.

Original languageEnglish
Article number113792
JournalGeneral and Comparative Endocrinology
Volume309
DOIs
StatePublished - Aug 1 2021

Keywords

  • Endocrine disruption
  • Environmental estrogens
  • Insulin-like growth factors
  • Oncorhynchus mykiss
  • Rainbow trout
  • Suppressor of cytokine signaling

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