Regulation of expression of Suppressors of Cytokine Signalling (SOCS) genes in hypothyroid male rats by Growth hormone, Thyroid Hormones and Estradiol

Abstract

SOCS proteins act as negative regulators of GH signalling. Recently, E2 was demonstrated to induce SOCS‐2 synthesis and inhibit GH signalling in liver and kidney cells. To evaluate the role of E2 on GH‐regulated SOCS in vivo, this work used orchidectomized‐hypothyroid (TX‐OX) male rats to minimize the influence of internal hormones on treatment. OX‐TX rats were treated 3 weeks with vehicle or E2 before hormonal replacement with GH, T3, or T3 plus GH during 7 days. We analyzed body growth, serum lipids and steady‐state levels of SOCS‐2, ‐3, and CIS mRNA expression in liver in relation to cited hormones. Hypothyroidism resulted in an over 2‐fold increase in serum cholesterol (Cho) levels and 2‐fold reduction in serum triglyceride (Tg) levels. T3 treatment decreased Cho and GH treatment resulted in 3‐4‐fold reduction in serum FFAs levels. Hypothyroidism reduced the levels of SOCS‐2 and CIS mRNA and induced SOCS‐3. E2 reversed the effects of hypothyroidism on SOCS2 and CIS but not on SOCS3 mRNA levels. Unlike T3, the effects of hypothyroidism on SOCS2 and CIS mRNA levels were reversed by GH. T3 reversed the effects of hypothyroidism on SOCS3. Whereas E2 enhanced the effect of T3 on SOCS2 and CIS, T3 effect on SOCS3 was antagonized. These results indicate that SOCS are differently regulated in vivo and an important physiological role for E2, GH and T3 in maintaining levels of SOCS in male liver.