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Jianming Xu

Publications and source records attributed to Jianming Xu.

At least 37 records · Page 2Linked to original sources
PubMed2005

Effects of lead and cadmium nitrate on biomass and substrate utilization pattern of soil microbial communities.

A study was conducted to evaluate the effects of different concentrations of lead (Pb) and cadmium (Cd) applied as their nitrates on soil microbial biomass carbon (C(mic)) and nitrogen (N(mic)), and substrate utilization pattern of soil microbial communities. The C(mic) and N(mic) contents were determined at 0, 14, 28, 42 and 56 days after heavy metal application (DAA). The results showed a significant decline in the C(mic) for all Pb and Cd amended soils from the start to 28 DAA. From 28 to 56 DAA, C(mic) contents changed non-significantly for all other treatments except for 600 mgkg(-1) Pb and 100 mgkg(-1) Cd in which it declined significantly from 42 to 56 DAA. The N(mic) contents also decreased significantly from start to 28 DAA for all other Pb and Cd treatments except for 200 mgkg(-1) Pb which did not show significant difference from the control. Control and 200 mgkg(-1) Pb had significantly lower soil microbial biomass C:N ratio as compared with other Pb treatments from 14 to 42 DAA, however at 56 DAA, only 1000 mgkg(-1) Pb showed significantly higher C:N ratio compared with other treatments. No significant difference in C:N ratio for all Cd treated soils was seen from start to 28 DAA, however from 42 to 56 DAA, 100 mgkg(-1) Pb showed significantly higher C:N ratio compared with other treatments. On 56 DAA, substrate utilization pattern of soil microbial communities was determined by inoculating Biolog ECO plates. The results indicated that Pb and Cd addition inhibited the functional activity of soil microbial communities as indicated by the intensity of average well color development (AWCD) during 168 h of incubation. Multivariate analysis of sole carbon source utilization pattern demonstrated that higher levels of heavy metal application had significantly affected soil microbial community structure.

Biomass↗
PubMed2005

Effects of dissolved organic matter from sewage sludge on the atrazine sorption by soils.

The effects of dissolved organic matter (DOM), water soluble organic matter derived from sewage sludge, on the sorption of atrazine (2-chloro-4-ethylamino-6-isopropylamino-1,3,5-trazine) by soils were studied using a batch equilibrium technique. Six paddy soils, chosen so as to have different organic carbon contents, were experimented in this investigation. Atrazine sorption isotherms on soils were described by the linear equation, and the distribution coefficients without DOM (Kd) or with DOM (Kd*) were obtained. Generally, the values of Kd*/Kd initially increased and decreased thereafter with increasing DOM concentrations of 0-60 mg DOC x L(-1) in soil-solution system form. Critical concentrations of DOM (DOM(np)) were obtained where the value of Kd* was equal to Kd. The presence of DOM with concentrations lower than DOM(np) promoted atrazine sorption on soils (Kd* > Kd), whereas the presence of DOM with concentrations higher than DOM(np) tended to inhibit atrazine sorption (Kd* < Kd). Interestingly, DOM(np) for tested soils was negatively correlated to the soil organic carbon content, and the maximum of Kd*/Kd (i.e. Kmax) correlated positively with the maximum of DOM sorption on soil (Xmax). Further investigations showed that the presence of hydrophobic fraction of DOM evidently promoted the atrazine sorption on soils, whereas the presence of hydrophilic DOM fraction obviously tended to inhibit the atrazine sorption. Interactions of soil surfaces with DOM and its fractions were suggested to be the major processes determining atrazine sorption on soils. The results of this work provide a reference to the agricultural use of organic amendment such as sewage sludge for improving the availability of atrazine in soils.

Adsorption↗
PubMed2005

Dual functions of the steroid hormone receptor coactivator 3 in modulating resistance to thyroid hormone.

Mutations of the thyroid hormone receptor beta (TRbeta) gene cause resistance to thyroid hormone (RTH). RTH is characterized by increased serum thyroid hormone associated with nonsuppressible thyroid-stimulating hormone (TSH) and impaired growth. It is unclear how the actions of TRbeta mutants are modulated in vivo to affect the manifestation of RTH. Using a mouse model of RTH that harbors a knockin mutation of the TRbeta gene (TRbetaPV mouse), we investigated the effect of the steroid hormone receptor coactivator 3 (SRC-3) on RTH. In TRbetaPV mice deficient in SRC-3, dysfunction of the pituitary-thyroid axis and hypercholesterolemia was lessened, but growth impairment of RTH was worsened. The lessened dysfunction of the pituitary-thyroid axis was attributed to a significant decrease in growth of the thyroid and pituitary. Serum insulin-like growth factor 1 (IGF-1) was further reduced in TRbetaPV mice deficient in SRC-3. This effect led to reduced signaling of the IGF-1/phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway that is known to mediate cell growth and proliferation. Thus, SRC-3 modulates RTH by at least two mechanisms, one via its role as a receptor coregulator and the other via its growth regulatory role through the IGF-1/PI3K/AKT/mTOR signaling.

Body Weight↗
PubMed2005

Dynamic cell type specificity of SRC-1 coactivator in modulating uterine progesterone receptor function in mice.

Regulation of gene transcription by the progesterone receptor (PR) in cooperation with coactivator/corepressor complexes coordinates crucial processes in female reproduction. To investigate functional relationships between PR and steroid receptor coactivators (SRCs) in distinct cell types of uterine tissue during gene transcription, we generated a new transgenic mouse model utilizing a Progesterone Receptor Activity Indicator (PRAI) system that could monitor PR activity in vivo. The PRAI system consists of a modified PR bacterial artificial chromosome (BAC) clone in which the DNA binding domain of the PR was replaced with the yeast Gal4 DNA binding domain. A humanized green fluorescent protein (hrGFP) reporter controlled by the Upstream Activating Sequences for the Gal4 gene (UAS(G)) was inserted in tandem with the modified PR gene. Expression of hrGFP in the uterus demonstrated that the PRAI animal model faithfully replicated PR signaling under various endocrine states. Bigenic PRAI-SRC-1(-/-) mice revealed that SRC-1 modulates PR activity in the uterus in a cell-specific fashion and is involved in PR gene activation in stroma and myometrium of the uterus in response to estrogen and progesterone. In contrast, SRC-1 was involved in the down-regulation of PR target gene expression in the luminal and glandular epithelial compartments of the uterus after chronic progesterone treatment. Finally, we dissected the means by which SRC-1 dynamically regulates PR activity in each uterine cell compartment and demonstrated that it involves the differential ability of SRC-1 to modulate expression levels of distinct coactivators, corepressors, and PR in a cell-specific fashion.

Animals↗
PubMed2005

Genetic deletion of the repressor of estrogen receptor activity (REA) enhances the response to estrogen in target tissues in vivo.

We previously identified a coregulator, repressor of estrogen receptor activity (REA), that directly interacts with estrogen receptor (ER) and represses ER transcriptional activity. Decreasing the intracellular level of REA by using small interfering RNA knockdown or antisense RNA approaches in cells in culture resulted in a significant increase in the level of up-regulation of estrogen-stimulated genes. To elucidate the functional activities of REA in vivo, we have used targeted disruption to delete the REA gene in mice. The targeting vector eliminated, by homologous recombination, the REA exon sequences encoding amino acids 12 to 201, which are required for REA repressive activity and for interaction with ER. The viability of heterozygous animals was similar to that of the wild type, whereas homozygous animals did not develop, suggesting a crucial role for REA in early development. Female, but not male, heterozygous animals had an increased body weight relative to age-matched wild-type animals beginning after puberty. REA mRNA and protein levels in uteri of heterozygous animals were half that of the wild type, and studies with heterozygous animals revealed a greater uterine weight gain and epithelial hyperproliferation in response to estradiol (E2) and a substantially greater stimulation by E2 of a number of estrogen up-regulated genes in the uterus. Even more dramatic in REA heterozygous animals was the loss of down regulation by E2 of genes in the uterus that are normally repressed by estrogen in wild-type animals. Mouse embryo fibroblasts derived from heterozygous embryos also displayed a greater transcriptional response to E2. These studies demonstrate that REA is a significant modulator of estrogen responsiveness in vivo: it normally restrains estrogen actions, moderating ER stimulation and enhancing ER repression of E2-regulated genes.

Animals↗
PubMed2004

Nuclear hormone receptor coregulator GRIP1 suppresses, whereas SRC1A and p/CIP coactivate, by domain-specific binding of MyoD.

p160 coregulators were initially identified as nuclear hormone receptor coactivators. In this study, functional data demonstrate that members of the three p160 families can have opposing roles in regulating gene expression by the same transcription factor. Both SRC1A and p/CIP function as coactivators for MyoD-mediated transcription whereas GRIP1 acts negatively as a (co)repressor. SRC1A and p/CIP predominantly interact with distinct sites on the NH2-terminal activation domain of MyoD. GRIP1 binds to both these regions but it alone, and neither SRC1A nor p/CIP, also interacts with specific sites on MyoD that are critical for the binding of the essential MyoD coactivator, p300. This suggests that competition by GRIP1 for SRC1A, p/CIP, and p300 binding sites on a transcription factor may regulate the activity of the factor.

Animals↗
PubMed2004

Haploid inactivation of the amplified-in-breast cancer 3 coactivator reduces the inhibitory effect of peroxisome proliferator-activated receptor gamma and retinoid X receptor on cell proliferation and accelerates polyoma middle-T antigen-induced mammary tumorigenesis in mice.

The amplified-in-breast cancer 3 (AIB3) is a nuclear receptor coactivator amplified and overexpressed in human breast cancers. AIB3(-/-) mice die during gestation, whereas AIB3(+/-) mice exhibit normal development. Here, we demonstrate that AIB3 protein is mainly located in the nuclei of mammary epithelial cells and tumor cells and its levels are elevated in mammary epithelial cells at middle pregnant stage and in mammary tumor cells. To examine whether AIB3 reduction affects mammary tumorigenesis, we generated wild-type mouse mammary tumor virus/polyoma middle-T (WT/PyMT) and AIB3(+/-)/PyMT mice. Mammary tumor development in AIB3(+/-)/PyMT female and male mice was substantially accelerated compared with that in WT/PyMT mice, because of increased cell proliferation in early tumorigenic lesions, including ductal hyperplasia and mammary intraepithelial neoplasia. Tumor formation in nude mice that received premalignant AIB3(+/-)/PyMT mammary tissue was much faster than in nude mice that received transplants of premalignant WT/PyMT mammary tissue, which indicated that the accelerated tumorigenesis in AIB3(+/-)/PyMT mammary glands is due to a mammary epithelial autonomous defect. Expression of PyMT, estrogen receptor alpha and estrogen receptor alpha-regulated genes was unaffected in AIB3(+/-)/PyMT mammary glands, which suggests that the acceleration of mammary tumor formation in AIB3(+/-)/PyMT mice was not a consequence of changes in PyMT expression or in estrogen receptor function. Importantly, the inhibitory effects of peroxisome proliferator-activated receptor gamma (PPARgamma) and retinoid-X receptor (RXR) ligands on AIB3(+/-)/PyMT cell proliferation and the transcriptional function of PPARgamma in AIB3(+/-)/PyMT cells were reduced. Thus, AIB3 haplodeficiency may facilitate PyMT-induced tumorigenesis through a partial impairment of PPARgamma and RXR function. These results suggest that AIB3 may be a tumor suppressor that is required for the inhibition of cell proliferation by PPARgamma and RXR.

Animals↗
PubMed2004

In vivo activation of PPAR target genes by RXR homodimers.

The ability of a retinoid X receptor (RXR) to heterodimerize with many nuclear receptors, including LXR, PPAR, NGF1B and RAR, underscores its pivotal role within the nuclear receptor superfamily. Among these heterodimers, PPAR:RXR is considered an important signalling mediator of both PPAR ligands, such as fatty acids, and 9-cis retinoic acid (9-cis RA), an RXR ligand. In contrast, the existence of an RXR/9-cis RA signalling pathway independent of PPAR or any other dimerization partner remains disputed. Using in vivo chromatin immunoprecipitation, we now show that RXR homodimers can selectively bind to functional PPREs and induce transactivation. At the molecular level, this pathway requires stabilization of the homodimer-DNA complexes through ligand-dependent interaction with the coactivator SRC1 or TIF2. This pathway operates both in the absence and in the presence of PPAR, as assessed in cells carrying inactivating mutations in PPAR genes and in wild-type cells. In addition, this signalling pathway via PPREs is fully functional and can rescue the severe hypothermia phenotype observed in fasted PPARalpha-/- mice. These observations have important pharmacological implications for the development of new rexinoid-based treatments.

Alitretinoin↗
PubMed2004

Partially redundant functions of SRC-1 and TIF2 in postnatal survival and male reproduction.

Both SRC-1 and TIF2 are members of the p160 steroid receptor coactivator family. Genetic analyses have shown that inactivation of TIF2, but not SRC-1, reduces postnatal survival, growth, and male reproductive function. Here, we demonstrate that, through analyses of SRC-1/TIF2 compound mutant mice, SRC-1 can partially compensate for the effects of a loss of TIF2 on mouse survival and growth, whereas SRC-1 and TIF2 are dispensable for primary organogenesis. The highly variable onset of defects observed in TIF2(-/-) testes due to the absence of TIF2 in Sertoli cells, including abnormal spermiogenesis, age-dependent degeneration of seminiferous epithelium, and disorder of cholesterol homeostasis, is uniformly accelerated upon inactivation of SRC-1 alleles in the TIF2 null genetic background, thus demonstrating that TIF2 and SRC-1 can perform redundant functions in Sertoli cells. Massive desquamation of immature germ cells together with an increase in germ cell apoptosis and a decrease in germ cell proliferation may be responsible for the early onset of the severe seminiferous epithelial degeneration observed in SRC-1(+/-)/TIF2(-/-) testes. Interestingly, the overall abnormal features displayed by the SRC-1(+/-)/TIF2(-/-) and SRC-1(-/-)/TIF2(-/-) mutant testes, including spermatid maturation defects, increase in Sertoli cell lipid stores, loss of immature germ cells, and formation of giant multinucleated spermatids, are commonly detected in testes of elderly men, suggesting that deficiencies in molecular pathways involving TIF2 and SRC-1 in Sertoli cells could participate in testicular senescence.

Aging↗
PubMed2004

AIB1/SRC-3 deficiency affects insulin-like growth factor I signaling pathway and suppresses v-Ha-ras-induced breast cancer initiation and progression in mice.

Although the amplified in breast cancer 1 (AIB1) coactivator is amplified and overexpressed in breast cancers, its role in mammary carcinogenesis remains unknown. We demonstrate that during mammary development and tumorigenesis, the elevation of AIB1 level and its nuclear localization correlate with normal and transformed mammary epithelial proliferation, whereas its lower expression and cytoplasmic localization correlate with mammary epithelial quiescence and differentiation. In this study, the role of AIB1 in breast tumor initiation, progression, and metastasis was studied by generating AIB1(+/+), AIB1(+/-), and AIB1(-/-) mice harboring the mouse mammary tumor virus/v-Ha-ras (ras) transgene that induces breast tumors. Breast tumor incidence was reduced dramatically in the intact AIB1(-/-)-ras virgin mice and inhibited completely in the ovariectomized AIB1(-/-)-ras mice. Breast tumor latency was delayed significantly in AIB1(-/-)-ras virgin mice with natural estrous cycles, multiparous mice with cyclically elevated reproductive hormones, and virgin mice bearing pituitary isografts with persistently elevated hormones. Although AIB1 deficiency significantly suppressed mammary tumorigenesis under all of the concentrations of ovarian hormones, it did not affect the promotional role of ovarian hormones on mammary tumorigenesis, suggesting that AIB1 and ovarian hormones contribute to mammary carcinogenesis through different pathways. AIB1 deficiency did not alter the expression of estrogen and progesterone-responsive genes in the mammary gland, but it caused partial resistance to the insulin-like growth factor I because of a significant reduction in the insulin receptor substrates. The impaired insulin-like growth factor I pathway in AIB1(-/-)-ras mammary epithelium and tumor cells was responsible in part for the suppression of mammary tumorigenesis and metastasis caused by inhibition of cell proliferation and migration. These results suggest that a more effective strategy to control breast cancer is to target AIB1-mediated and ovarian hormone-initiated pathways.

Animals↗
PubMed2004

Effects of land management change on spatial variability of organic matter and nutrients in paddy field: a case study of Pinghu, China.

The Household Responsibility System initiated in the late 1970s in China has brought a profound change to its rural economy. The shift from the collective farming system to individual family farms has changed land management. The change, including fertilization and crop systems, may have significant effects on soil quality and agro-environmental sustainability. However, very little research is being carried out on the impact of reformed land tenure systems on the spatial variability of soil nutrients. In this study, geostatistics was applied to analyze changes in the spatial variability of soil organic matter and nutrients in paddy fields in Pinghu County, China after 20 years of land management change. In 1984 and 2002, 617 and 131 locations were selected, respectively, for collecting surface soil samples to analyze soil organic matter (SOM), total nitrogen (TN), available phosphorus (AP), and available potassium (AK). From 1984 to 2002, variability of the SOM and TN changed from strongly to moderately spatial-dependent, and the variability of AP remained weakly dependent on space, but that of the AK changed from moderately to weakly spatial-dependent. That the trend of the variability of four soil properties in 2002 became weaker than that in 1984 showed that the extrinsic factors (soil management practices, such as fertilization) weakened the effect by intrinsic factors (soil formation factors, such as soil parent materials) owing to a long period of land management change. The temporal geographic maps of the SOM and nutrients spatial distributions suggested that the concentrations of the SOM and nutrients had been changed to different extents during the period. Significant increase in AP and decrease in AK were noted. The changes were likely due to the imbalance between N, P, and K fertilizers and increased grain yield.

Agriculture↗
PubMed2004

Nuclear receptor coregulators are new players in nervous system development and function.

Steroid/thyroid hormones and their cognate nuclear receptors (NRs) play important roles in nervous system development and function. The spatial and temporal gene expression that is regulated by NRs in the nervous system requires transcriptional intermediary coregulators, designated as coactivators and corepressors. These coregulators enhance or repress transcriptional activity of NRs and modulate their target gene transcription. Recent progress has largely advanced our understanding of the molecular mechanisms by which NR coregulators function in the nervous system. This article summarizes our current knowledge about the molecular mechanisms, expression patterns, and biological functions of NR coactivators, such as the p160 steroid receptor coactivator family, CBP, p300, BRG1, TRAP220, PGC-1alpha, ERAP140, NIX1, and E6-AP, as well as corepressors such as NCoR and SMRT. Accumulated findings suggest that the functional spectrum of NR coregulators is much broader than was initially speculated, and these coregulators likely contribute to many physiological aspects of nervous system development and function.

Animals↗
PubMed2003

Interactions between activating signal cointegrator-2 and the tumor suppressor retinoblastoma in androgen receptor transactivation.

Activating signal cointegrator-2 (ASC-2), a cancer-amplified transcription coactivator of nuclear receptors and numerous other transcription factors, was previously shown to contain two LXXLL motifs, each of which interacts with a distinct set of nuclear receptors. In this work, we showed that ASC-2 has an indirect, separate binding site for androgen receptor (AR). Interestingly, this region overlapped with the direct interaction interfaces with the tumor suppressor retinoblastoma (Rb). Although ASC-2 alone stimulated AR transactivation in cotransfections of HeLa cells, ectopic expression of Rb effected ASC-2 to act as a transcription coactivator of AR in Rb-null Saos2 cells. These results, along with the previous report in which AR was shown to directly interact with Rb (Yeh, S., Miyamoto, H., Nishimura, K., Kang, H., Ludlow, J., Hsiao, P., Wang, C., Su, C., and Chang C. (1998) Biochem. Biophys. Res. Commun. 248, 361-367), suggest that the AR-ASC-2 interactions in vivo may involve Rb. Thus, ASC-2 appears to contain at least three distinct nuclear receptor interaction domains.

Amino Acid Motifs↗
PubMed2003

Effects of loss of steroid receptor coactivator-1 on the skeletal response to estrogen in mice.

Steroid receptor coactivator (SRC)-1 is an important nuclear receptor coactivator that enhances estrogen (E) action in many tissues, but its role in mediating E effects on bone is unknown. Thus, we assessed the skeletal response to ovariectomy (ovx) and E replacement in SRC-1 knockout (KO) mice compared with wild-type (WT) littermates. Bone mineral density was measured by dual-energy x-ray absorptiometry and peripheral quantitative computed tomography at baseline and after 2 months of sham surgery, ovx, or ovx plus E replacement. Microcomputed tomography and bone histomorphometry were also performed at the end of the study. Both WT and SRC-1 KO mice lost bone at multiple sites after ovx; however, although an estradiol (E(2)) dose of 10 microg/kg.d completely prevented loss of cancellous bone (at the lumbar spine and tibial metaphysis) in the WT mice, it was entirely ineffective in preventing cancellous bone loss at these sites in the SRC-1 KO mice. This E(2) dose was, however, equally effective on cortical bone in the tibia in the SRC-1 KO and WT mice. Moreover, a 4-fold higher dose of E(2) was able to overcome the deficit in E action in cancellous bone in the SRC-1 KO mice. These findings establish that, in mice, loss of SRC-1 leads to skeletal resistance to E predominantly in cancellous bone.

Absorptiometry, Photon↗
PubMed2003

Review of the in vivo functions of the p160 steroid receptor coactivator family.

The p160 steroid receptor coactivator (SRC) gene family contains three homologous members, which serve as transcriptional coactivators for nuclear receptors and certain other transcription factors. These coactivators interact with ligand-bound nuclear receptors to recruit histone acetyltransferases and methyltransferases to specific enhancer/promotor regions, which facilitates chromatin remodeling, assembly of general transcription factors, and transcription of target genes. This minireview summarizes our current knowledge about the molecular structures, molecular mechanisms, temporal and spatial expression patterns, and biological functions of the SRC family. In particular, this article highlights the roles of SRC-1 (NCoA-1), SRC-2 (GRIP1, TIF2, or NCoA-2) and SRC-3 (p/CIP, RAC3, ACTR, AIB1, or TRAM-1) in development, organ function, endocrine regulation, and nuclear receptor function, which are defined by characterization of the genetically manipulated animal models. Furthermore, this article also reviews our current understanding of the role of SRC-3 in breast cancer and discusses possible mechanisms for functional specificity and redundancy among SRC family members.

Acetyltransferases↗
PubMed2003

Regulation of expression of thyroid hormone receptor isoforms and coactivators in liver and heart by thyroid hormone.

Autoregulation of thyroid hormone (TH) receptors (TRs) is a mechanism whereby a cell can regulate its responsiveness to TH. Nuclear coactivators (NCoAs) modulate TH action and may also be important for regulation of TR expression. We have determined the effect of TH withdrawal and treatment on the expression of different isoforms of TR as well as expression of the NCoAs SRC-1, TIF-2 and SRC-3 using quantitative real time polymerase chain reaction. In order to identify the effect that each TR isoform exerts over the expression of the other, NCoA and TR transcripts were measured in liver and heart tissue from wild type mice or mice with deletion of either TR isoform or SRC-1 genes. In liver, regulation of TR beta1 and TR alpha2 subtype expression is inversely related to TH levels and the regulation of TR beta expression is, in part, controlled by TR alpha. In the heart, the opposite is the case, regulation of TR alpha2 and TR beta1 isoform expression is directly related to TH levels and this regulation is primarily controlled by TR alpha. Although NCoAs are, in general, increased in response to hypothyroidism or in states of TH resistance, SRC-1 specifically does not regulate TR isoform expression. We have demonstrated that TR isoforms and NCoAs are autoregulated transcription factors with tissue specificity.

Animals↗
PubMed2003

Thyroid hormone receptor-specific interactions with steroid receptor coactivator-1 in the pituitary.

Steroid receptor coactivator-1 (SRC-1) is a transcription cofactor that enhances the hormone-dependent action mediated by the thyroid hormone (TH) receptor (TR) as well as other nuclear receptors. However, it is not known whether the SRC-1-mediated activation of TH-regulated gene transcription is TR isoform specific in the pituitary. We generated mice that were deficient in TRalpha and SRC-1 (TRalpha(0/0)SRC-1(-/-)), as well in TRbeta and SRC-1 (TRbeta(-/-)SRC-1(-/-)), and thyroid function tests and effects of TH deprivation and TH treatment were compared with wild-type mice or mice with deletion of either TRs or SRC-1 alone. We have shown that 1) TRbeta(-/-)SRC-1(-/-) mice demonstrate more severe TH resistance than either the SRC-1(-/-) or TRbeta(-/-) mice; the additive effect indicates that SRC-1 has an independent role in TH action over that of TRbeta; 2) SRC-1 facilitates TRbeta and TRalpha-mediated down-regulation of TSH, as TRalpha(0/0)SRC-1(-/-) mice demonstrate TH resistance rather than hypersensitivity as seen in TRalpha(0/0)mice; and 3) a compensatory increase in SRC-1 expression is associated with the TH hypersensitivity seen in TRalpha-deficient animals. We conclude that SRC-1 action in the pituitary mediates TH action via specific TR subtypes.

Animals↗