title: Environmental estrogens inhibit mRNA and functional expression of growth hormone receptors as well as growth hormone signaling pathways in vitro in rainbow trout (Oncorhynchus mykiss).
abstract: Fish in aquatic habitats are exposed to increasing concentrations and types of environmental contaminants, including environmental estrogens (EE). While there is growing evidence to support the observation that endocrine-disrupting compounds (EDCs) possess growth-inhibiting effects, the mechanisms by which these physiological effects occur are poorly understood. In this study, we examined the direct effects of EE, specifically 17β-estradiol (E2), β-sitosterol (βS), and 4-n-nonylphenol (NP), on GH sensitivity as assessed by mRNA expression and functional expression of growth hormone receptor in hepatocytes, gill filaments, and muscle in rainbow trout (Oncorhynchus mykiss). Additionally, we examined the effects of EE on signaling cascades related to growth hormone signal transduction (i.e., JAK-STAT, MAPK, and PI3K-Akt). Environmental estrogens directly suppressed the expression of GHRs in a tissue- and compound-related manner. The potency and efficacy varied with EE; effects were most pronounced with E2 in liver. EE treatment deactivated the JAK-STAT, MAPK, and PI3K-Akt pathways in liver a time-, EE- and concentration-dependent manner. Generally, E2 and NP were most effective in deactivating pathway elements; maximum suppression for each pathway was rapid, typically occurring at 10-30min. The observed effects occurred via an estrogen-dependent pathway, as indicated by treatment with an ER antagonist, ICI 182,780. These findings suggest that EEs suppress growth by reducing GH sensitivity in terms of reduced GHR synthesis and reduced surface GHR expression and by repressing GH signaling pathways.
authors.affiliation: Department of Biological Sciences, North Dakota State University, Fargo 58108, USA.
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Hanson
authors.affiliation: Department of Biological Sciences, North Dakota State University, Fargo 58108, USA.
authors.forename: Alicia T
authors.initials: AT
authors.lastname: Ickstadt
authors.affiliation: Department of Biological Sciences, North Dakota State University, Fargo 58108, USA.
authors.forename: Dillon J
authors.initials: DJ
authors.lastname: Marquart
authors.affiliation: Department of Biological Sciences, North Dakota State University, Fargo 58108, USA.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Kittilson
authors.affiliation: Department of Biological Sciences, North Dakota State University, Fargo 58108, USA. Electronic address: mark.sheridan@ttu.edu.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Sheridan
mesh_terms: D000818:Animals; D015153:Blotting, Western; D004781:Environmental Exposure; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D065171:Estrogen Receptor Antagonists / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D000077267:Fulvestrant; D005786:Gene Expression Regulation / Q000187:drug effects*; D005880:Gills / Q000187:drug effects / Q000378:metabolism; D013006:Growth Hormone / Q000378:metabolism*; D000960:Hypolipidemic Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D009132:Muscles / Q000187:drug effects / Q000378:metabolism; D017686:Oncorhynchus mykiss / Q000254:growth & development / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D011986:Receptors, Somatotropin / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*; D012855:Sitosterols / Q000494:pharmacology
chemical_list: D065171:Estrogen Receptor Antagonists; D004967:Estrogens; D000960:Hypolipidemic Agents; D012333:RNA, Messenger; D011986:Receptors, Somatotropin; D012855:Sitosterols; D000077267:Fulvestrant; D004958:Estradiol; C025473:gamma-sitosterol; D013006:Growth Hormone
keywords: Environmental estrogens; Growth hormone receptor; Growth hormone signaling