Environmental estrogens inhibit insulin-like growth factor (IGF) receptor mRNA expression, IGF binding, and IGF signaling ex vivo in rainbow trout (Oncorhynchus mykiss).
Gen Comp Endocrinol
; 330: 114125, 2023 01 01.
Article
in En
| MEDLINE
| ID: mdl-36116484
ABSTRACT
In this study, we used juvenile rainbow trout to examine the direct effects of selected environmental estrogens (EE), specifically, 17 ß-estradiol (E2), ß-sitosterol (ßS), and 4-n-nonylphenol (NP), on target tissue sensitivity to insulin-like growth factor (IGF) as assessed by expression of IGF receptor type 1 (IGFR1) mRNAs and IGF-1 binding capacity, as well as on the cell signaling pathways through which EE exert their effects. E2 and NP inhibited IGFR1A and IGFR1B mRNA expression in a time- and concentration-related manner in gill and muscle; however, ßS had no effect on expression of IGFR1 mRNAs in either tissue. NP reduced 125I-IGF binding in gill and E2 and NP reduced 125I-IGF in white muscle; ßS had no effect on 125I-IGF binding in either gill or white muscle. Treatment of gill filaments with either E2 or NP rapidly deactivated (via reduced proportion of phosphorylation) JAK2, STAT5, Akt, and ERK; ßS had no effect on the activation state of any cell signaling elements tested. The effects of EE on IGFR mRNA expression in gill were estrogen receptor (ER) dependent as the inhibitory effects were rescued by the ER antagonist, ICI 182,780. All EE tested blocked growth hormone (GH)-stimulated IGFR mRNA expression in gill filaments. GH-stimulated activation of JAK2, STAT5, Akt, and ERK were blocked by E2, ßS, and NP. Lastly, E2 and NP stimulated suppressor of cytokine signaling 2 (SOCS-2) mRNA expression, an effect that also was ER dependent. These results indicate that EE directly reduce the sensitivity of peripheral tissues to IGF by reducing mRNA and functional expression of IGFRs. Such inhibitory actions of EE are mediated, at least in part, by ER-dependent mechanisms that deactivate JAK, STAT, Akt, and ERK and enhance expression of SOCS-2. These findings together with our previous results show that EE retard growth of post-embryonic rainbow trout through widespread direct effects on the GH-IGF system, specifically, by reducing tissue sensitivity to GH, inhibiting IGF production, reducing tissue sensitivity to IGF, and by deactivating post-receptor IGF cell signaling pathways.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Oncorhynchus mykiss
Limits:
Animals
Language:
En
Journal:
Gen Comp Endocrinol
Year:
2023
Document type:
Article
Affiliation country:
United States