Faculty Opinions recommendation of Resurrecting the ancestral steroid receptor: ancient origin of estrogen signaling.

2003 ◽  
Author(s):  
Thomas Mitchell-Olds
Keyword(s):  
Steroid Receptor ◽  
Estrogen Signaling

scholarly journals Estrogen-Regulated Prohibitin Is Required for Mouse Uterine Development and Adult Function

Endocrinology ◽  
2011 ◽  
Vol 152 (3) ◽  
pp. 1047-1056 ◽  
Author(s):  
Bin He ◽  
Tae Hoon Kim ◽  
Ramakrishna Kommagani ◽  
Qin Feng ◽  
Rainer B. Lanz ◽  
...  
Keyword(s):  
Target Genes ◽  
Cultured Cells ◽  
Physiological Role ◽  
Reproductive Function ◽  
Steroid Receptor ◽  
Estrogen Signaling ◽  
Steroid Receptor Coactivator ◽  
Regulated Gene Expression ◽  
Uterine Development

Estrogen signaling is pivotal for maintenance of female reproductive function in mammals. The physiological role of estrogen is mediated by estrogen receptors (ERs) and the steroid receptor coactivator family of transcriptional coregulators. Ablation of steroid receptor coactivator and ER coactivators in mice causes impaired female reproductive function. Recently we reported that prohibitin (PHB) can function as a corepressor for ERs in cultured cells. In this study, we demonstrate that PHB is an estrogen-regulated gene in vitro and in vivo, and its expression is induced by estrogen in the uterus, suggesting the existence of feedback regulatory loops. A conditional PHB knockout mouse model was generated by gene targeting to assess its in vivo function. Female mice with selective ablation of the PHB allele in the uterus were sterile, and their uteri were severely hypoplastic, indicating PHB is required for uterine development. Moreover, expression of ER and progesterone receptor target genes was selectively altered in response to hormone treatment. In summary, this study demonstrates that PHB is an estrogen-regulated gene and that PHB is essential for mouse uterine development and adult function and selectively required for estrogen-regulated gene expression.

scholarly journals Signaling within a Coactivator Complex: Methylation of SRC-3/AIB1 Is a MolecularSwitch for Complex Disassembly

2006 ◽  
Vol 26 (21) ◽  
pp. 7846-7857 ◽  
Author(s):  
Qin Feng ◽  
Ping Yi ◽  
Jiemin Wong ◽  
Bert W. O'Malley
Keyword(s):  
Estrogen Receptor Alpha ◽  
Steroid Receptor ◽  
In Vitro Transcription ◽  
Estrogen Signaling ◽  
Dual Function ◽  
Mcf7 Cells ◽  
Transcriptional Initiation ◽  
Coactivator Complex

ABSTRACT Recent studies indicate that steroid receptor-mediated transcriptional initiation is a cyclical process involving multiple rounds of coactivator assembly and disassembly. Steroid receptor coactivator 3 (SRC-3) coactivator phosphorylation has been shown to regulate coactivator complex assembly, but the mechanisms by which coactivator disassembly is triggered are not well understood. In this study, we provide in vitro and in vivo evidence that members of the SRC coactivator family serve as substrates for the enzymatic coactivator coactivator-associated arginine methyltransferase 1 (CARM1). Methylation of SRC-3 was localized to an arginine in its CARM1 binding region and correlated with decreased estrogen receptor alpha-mediated transcription, as seen with both cell-based and in vitro transcription assays. Consistent with this finding, we demonstrated that methylation promotes dissociation of the SRC-3/CARM1 coactivator complex. Methylation of SRC-3 is regulated by estrogen signaling in MCF7 cells and serves as a molecular switch for disassembly of the SRC-3 transcriptional coactivator complex. We propose that CARM1 is a dual-function coactivator, as it not only activates transcription by modifying core histone tails but also terminates hormone signaling by disassembly of the coactivator complex.

scholarly journals Interaction of steroid receptor coactivators and estrogen receptors in the human placenta

2016 ◽  
Vol 56 (3) ◽  
pp. 239-247 ◽  
Author(s):  
Seung Chul Kim ◽  
Mee-Na Park ◽  
Young Joo Lee ◽  
Jong Kil Joo ◽  
Beum-Soo An
Keyword(s):  
Estrogen Receptors ◽  
Human Placenta ◽  
Late Stage ◽  
Clock Gene ◽  
Steroid Receptor ◽  
Estrogen Signaling ◽  
Specific Effects ◽  
Gestation Age ◽  
Steroid Receptor Coactivators ◽  
Estrogen Concentration

Female sex steroid hormones such as estrogen and progesterone have a pivotal role in maintaining pregnancy in human and animals. Especially, estrogen exerts specific effects on the cardiovascular system and angiogenesis, and thus affects significantly on placentation. Although the functions of estrogen have been emphasized during pregnancy, their signaling pathways in the placenta have not been fully understood. In this study, estrogen signaling was evaluated according to gestational age. Human placenta samples were collected and divided into early preterm (n=10), late preterm (n=18), and term (n=20) groups. First, serum estrogen concentration and corticotropin-releasing hormone (CRH) mRNA expression, which is known as gestation clock gene, were increased following gestation age in our experimental condition, as we expected. Next, the expression of estrogen receptors (ERs) and steroid receptor coactivators (SRCs) in the placenta was evaluated. ERα (ESR1) and ERβ (ESR2) were expressed highly at term period compared with early preterm. In addition, SRC family including SRC1, SRC2, and SRC3 was expressed in the human placenta, and the levels of SRC1, SRC2, and SRC3 were increased in the placenta at the late stage of gestation. The interaction of ERs with SRCs was also examined, which was significantly enhanced at term period. In the immunostaining results, it was indicated that ERs and SRCs were all dominantly expressed in syncytiotrophoblast cells. These results suggested that SRC1, SRC2, and SRC3 were expressed and interact with ERs highly at the late stage of gestation, and may amplify the signaling of estrogen in the placenta to maintain pregnancy.

Regulation of steroid receptor signalling by tumor suppressor INPP4B

2017 ◽  
Author(s):  
Manqi Zhang ◽  
Egla Suarez ◽  
Lubov Nathanson ◽  
Michael Ittmann ◽  
Nancy Weigel ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Steroid Receptor ◽  
Receptor Signalling

Membrane estrogen receptor α is essential for estrogen signaling in the male skeleton

2018 ◽  
Vol 239 (3) ◽  
pp. 303-312 ◽  
Author(s):  
H H Farman ◽  
K L Gustafsson ◽  
P Henning ◽  
L Grahnemo ◽  
V Lionikaite ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Estrogen Receptor Α ◽  
Estrogen Signaling ◽  
Areal Bone Mineral Density ◽  
Male Mice ◽  
Mineral Density ◽  
Intact Male ◽  
Trabecular Thickness ◽  
Total Body

The importance of estrogen receptor α (ERα) for the regulation of bone mass in males is well established. ERα mediates estrogenic effects both via nuclear and membrane-initiated ERα (mERα) signaling. The role of mERα signaling for the effects of estrogen on bone in male mice is unknown. To investigate the role of mERα signaling, we have used mice (Nuclear-Only-ER; NOER) with a point mutation (C451A), which results in inhibited trafficking of ERα to the plasma membrane. Gonadal-intact male NOER mice had a significantly decreased total body areal bone mineral density (aBMD) compared to WT littermates at 3, 6 and 9 months of age as measured by dual-energy X-ray absorptiometry (DEXA). High-resolution microcomputed tomography (µCT) analysis of tibia in 3-month-old males demonstrated a decrease in cortical and trabecular thickness in NOER mice compared to WT littermates. As expected, estradiol (E2) treatment of orchidectomized (ORX) WT mice increased total body aBMD, trabecular BV/TV and cortical thickness in tibia compared to placebo treatment. E2 treatment increased these skeletal parameters also in ORX NOER mice. However, the estrogenic responses were significantly decreased in ORX NOER mice compared with ORX WT mice. In conclusion, mERα is essential for normal estrogen signaling in both trabecular and cortical bone in male mice. Increased knowledge of estrogen signaling mechanisms in the regulation of the male skeleton may aid in the development of new treatment options for male osteoporosis.

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