Spatiotemporal expression patterns of histone acetyltransferase steroid receptor coactivator-1 in developing mouse heart

Abstract Mutations in the thyroid hormone receptor-β gene (TRβ) cause resistance to thyroid hormone. How the action of mutant thyroid hormone nuclear receptors (TRs) is regulated in vivo is not clear. We examined the effect of a TR coactivator, steroid receptor coactivator-1 (SRC-1), on target-tissue responsiveness by using a mouse model of resistance to thyroid hormone, TRβPV knockin mice, in the SRC-1 null background. Lack of SRC-1 intensified the dysfunction of the pituitary-thyroid axis and impaired growth in TRβPV/+ mice but not in TRβPV/PV mice. In TRβPV/PV mice, however, lack of SRC-1 intensified the pathological progression of thyroid follicular cells to papillary hyperplasia, reminiscent of papillary neoplasia. In contrast, lack of SRC-1 did not affect responsiveness in the liver in regulating serum cholesterol in either TRβPV/+ or TRβPV/PV mice. Lack of SRC-1 led to changes in the abnormal expression patterns of several T3 target genes in the pituitary and liver. Thus, the present studies show that a coactivator such as SRC-1 could modulate the in vivo action of TRβ mutants in a tissue-dependent manner.

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Ligand-Controlled Interaction of Histone Acetyltransferase Binding to ORC-1 (HBO1) with the N-Terminal Transactivating Domain of Progesterone Receptor Induces Steroid Receptor Coactivator 1-Dependent Coactivation of Transcription

Molecular Endocrinology ◽

10.1210/me.2005-0149 ◽

2006 ◽

Vol 20 (9) ◽

pp. 2122-2140 ◽

Cited By ~ 47

Author(s):

Maria Georgiakaki ◽

Nathalie Chabbert-Buffet ◽

Boris Dasen ◽

Geri Meduri ◽

Sandra Wenk ◽

...

Keyword(s):

Progesterone Receptor ◽

Histone Acetyltransferase ◽

Steroid Receptor ◽

Steroid Receptor Coactivator

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Steroid Receptor Coactivator Expression throughout the Menstrual Cycle in Normal and Abnormal Endometrium

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.87.6.8572 ◽

2002 ◽

Vol 87 (6) ◽

pp. 2960-2966 ◽

Cited By ~ 71

Author(s):

Christopher W. Gregory ◽

Elizabeth M. Wilson ◽

K. B. C. Apparao ◽

Ruth A. Lininger ◽

William R. Meyer ◽

...

Keyword(s):

Menstrual Cycle ◽

Endometrial Hyperplasia ◽

Clomiphene Citrate ◽

Expression Patterns ◽

Steroid Receptor ◽

Male Factor ◽

Steroid Receptor Coactivator ◽

Additional Group ◽

Steroid Receptor Coactivators ◽

Fertile Women

The endometrium of reproductive aged women undergoes cyclic developmental changes in preparation for implantation in response to estrogen and progesterone. These steroids and their receptors are tightly regulated throughout the menstrual cycle, and their actions are facilitated by the presence of steroid receptor coactivators of the p160 family. In this study using immunohistochemistry and Western blot analysis, we characterize the expression patterns of three coactivators, steroid receptor coactivator-1, amplified in breast cancer-1 (AIB1), and transcriptional intermediary factor-2 in human endometrium obtained prospectively from normal fertile women throughout the menstrual cycle. With the exception of glandular AIB1, which increased in the late secretory phase, none of the coactivators changed significantly during the menstrual cycle. We compared coactivator expression patterns in fertile endometrium to the endometrium of anovulatory (proliferative; n = 3) and clomiphene-induced ovulatory (secretory; n = 13) women with polycystic ovarian syndrome (PCOS), a group that have a higher likelihood of developing estrogen-induced endometrial hyperplasia and cancer. To control for the effect of clomiphene citrate, an additional group was included consisting of ovulatory women treated with clomiphene citrate for “male factor” infertility. Compared with both fertile and infertile controls, PCOS women exhibited elevated levels of AIB1 and transcriptional intermediary factor-2 expression in both epithelial and stromal cells. We postulate that increased coactivator expression may render the endometrium more sensitive to estrogen. In support of this, we describe an increased expression of ERα (an estrogen-induced gene product) during the menstrual cycle in PCOS endometrium compared with fertile controls. In summary, we demonstrate that the expression of p160 coactivators are regulated in endometrium during the menstrual cycle in normal fertile women but are overexpressed in the endometrium of women with PCOS. Based on these findings, we suggest a possible mechanism to explain the poor reproductive performance observed in PCOS and the increased incidence of endometrial hyperplasia and cancer noted in this group of women.

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Review of the in Vivo Functions of the p160 Steroid Receptor Coactivator Family

Molecular Endocrinology ◽

10.1210/me.2003-0116 ◽

2003 ◽

Vol 17 (9) ◽

pp. 1681-1692 ◽

Cited By ~ 336

Author(s):

Jianming Xu ◽

Qingtian Li

Keyword(s):

Transcription Factors ◽

Nuclear Receptors ◽

Molecular Mechanisms ◽

Target Genes ◽

Current Knowledge ◽

Expression Patterns ◽

Steroid Receptor ◽

Molecular Structures ◽

Endocrine Regulation ◽

Steroid Receptor Coactivator

Abstract 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.

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