Manipulation of thyroid status and/or GH injection alters hepatic gene expression in the juvenile chicken

Abstract

Both thyroid hormone (T₃) and growth hormone (GH) are important regulators of somatic growth in birds and mammals. Although T₃-mediated gene transcription is well known, the molecular basis of T₃interaction with GH on growth and development of birds remains unknown. In earlier studies, we discovered that exogenous GH alone increased accumulation of visceral fat in young chickens, while the combination of GH injections and dietary T₃ worked synergistically to deplete body fat. In the present study, cDNA microarray and quantitative RT-PCR analyses enabled us to examine hepatic gene expression in young chickens after chronic manipulation of thyroid status and GH injection alone or in combination with T₃. Thyroid status modulates expression of common and unique sets of genes involved in a wide range of molecular functions (i.e., energy metabolism, storage and transport, signal transduction, protein turnover and drug detoxification). Hepatic expression of 35 genes was altered by hypothyroidism (e.g., ADFP, ANGPTL3, GSTΑ, CAT, PPARG, HMGCL, GHR, IGF1, STAT3, THRSPα), whereas hyperthyroidism affected expression of another cluster of 13 genes (e.g., IGFBP1, KHK, LDHB, BAIA2L1, SULT1B, TRIAD3). Several genes were identified which have not been previously ascribed as T₃ responsive (e.g., DEFB9, EPS8L2, ARHGAP1, LASS2, INHBC). Exogenous GH altered expression of 17 genes (e.g., CCAR1, CYP2C45, GYS2, ENOB, HK1, FABP1, SQLE, SOCS2, UPG2). The T₃+GH treatment depleted the greatest amount of body fat, where 34 differentially expressed genes were unique to this group (e.g., C/EBP, CDC42EP1, SYDE2, PCK2, PIK4CA, TH1L, GPT2, BHMT). The marked reduction in body fat brought about by the T₃+GH synergism could involve modulation of hormone signaling via altered activity of the Ras superfamily of molecular switches, which control diverse biological processes. In conclusion, this study provides the first global analysis of endocrine (T₃ and GH) regulation of hepatic gene transcription in the chicken.

Growth Hormone-Regulated mRNAs and miRNAs in Chicken Hepatocytes

“…Two DEG were involved in fat digestion and absorption. One of them is FABP1 , which is an important lipid-related gene [41] and has been shown to be up-regulated by GH in young chickens [42]. The other gene PPAP2B is involved in the glycerolipid metabolism pathway.…”

High-Resolution Mapping of Gene Expression Using Association in an Outbred Mouse Stock

“…We used the chromosome 6 locus as an example and were able to resolve the 14 distant eQTL into several groups based on which marker they associated with most strongly. Among these, the group that showed significant association with the Pparg locus comprised three genes one of which (S3-12) has been associated with Pparg gene previously [19],[31] and another gene (Hmgcl) has been shown to be coregulated with Pparg at the transcript level by thyroid hormone [31].…”

Regulation of ANKRD9 expression by lipid metabolic perturbations

“…Therefore, we examined whether lipid metabolic perturbations are associated with changes in cANKRD9 mRNA abundance. Thyroid hormone T3 increases energy expenditure (4,5), reduces hepatic triglyceride content (6), and decreases body fat content (7). Chickens treated with dietary T3 showed decreased mRNA level of cANKRD9, compared with chickens fed the control diet (Fig.…”

“…The use of animals in these studies complies with the University of Delaware Animal Care and Use Guidelines. Experimental paradigms for thyroid hormone manipulation and nutritional management were described previously (7,8,29). Total RNA samples were isolated using RNeasy mini kit (Qiagen, Valencia, CA).…”