Nuclear receptor modulation – Role of coregulators in selective estrogen receptor modulator (SERM) actions

Feng, Qin; O’Malley, Bert W.

doi:10.1016/j.steroids.2014.06.008

Cited by 48 publications

(29 citation statements)

References 63 publications

(63 reference statements)

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“…RU486 or Mifepristone, a PR antagonist, demonstrated cell-line-specific agonist/antagonistic activities that resulted from the coactivator/corepressor ratio available in the respective cell lines (68). The same was also shown with tamoxifen, whose function was governed by the coactivator/corepressor ratio in breast cancer and uterine cell lines (51,69). …”

Section: Mechanisms For Sarm Tissue-selectivitymentioning

confidence: 54%

Development of selective androgen receptor modulators (SARMs)

Narayanan

Coss

Dalton

2018

Molecular and Cellular Endocrinology

193

139

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The Androgen Receptor (AR), a member of the steroid hormone receptor family, plays important roles in the physiology and pathology of diverse tissues. AR ligands, which include circulating testosterone and locally synthesized dihydrotestosterone, bind to and activate the AR to elicit their effects. Ubiquitous expression of the AR, metabolism and cross reactivity with other receptors limit broad therapeutic utilization of steroidal androgens. However, the discovery of selective androgen receptor modulators (SARMs) and other tissue-selective nuclear hormone receptor modulators that activate their cognate receptors in a tissue-selective manner provides an opportunity to promote the beneficial effects of androgens and other hormones in target tissues with greatly reduced unwanted side-effects. In the last two decades, significant resources have been dedicated to the discovery and biological characterization of SARMs in an effort to harness the untapped potential of the AR. SARMs have been proposed as treatments of choice for various diseases, including muscle-wasting, breast cancer, and osteoporosis. This review provides insight into the evolution of SARMs from proof-of-concept agents to the cusp of therapeutic use in less than two decades, while covering contemporary views of their mechanisms of action and therapeutic benefits.

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Section: Mechanisms For Sarm Tissue-selectivitymentioning

confidence: 54%

Development of selective androgen receptor modulators (SARMs)

Narayanan

Coss

Dalton

2018

Molecular and Cellular Endocrinology

193

139

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“…Several studies have highlighted the role of coregulators in total transcriptional activity of steroid hormone receptors (Evers et al 2014a, Feng & O'Malley 2014. However, most of these studies have been carried out in mammary and uterine normal tissues or tumor tissues (Evers et al 2014a,b, Feng & O'Malley 2014, Szwarc et al 2014.…”

Section: R255mentioning

confidence: 99%

Molecular aspects of bovine cystic ovarian disease pathogenesis

Ortega¹,

Marelli²,

Rey³

et al. 2015

Reproduction

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Cystic ovarian disease (COD) is one of the main causes of reproductive failure in cattle and causes severe economic loss to the dairy farm industry because it increases both days open in the post partum period and replacement rates due to infertility. This disease is the consequence of the failure of a mature follicle to ovulate at the time of ovulation in the estrous cycle. This review examines the evidence for the role of altered steroid and gonadotropin signaling systems and the proliferation/apoptosis balance in the ovary with cystic structures. This evidence suggests that changes in the expression of ovarian molecular components associated with these cellular mechanisms could play a fundamental role in the pathogenesis of COD. The evidence also shows that gonadotropin receptor expression in bovine cystic follicles is altered, which suggests that changes in the signaling system of gonadotropins could play a fundamental role in the pathogenesis of conditions characterized by altered ovulation, such as COD. Ovaries from animals with COD exhibit a disrupted steroid receptor pattern with modifications in the expression of coregulatory proteins. These changes in the pathways of endocrine action would trigger the changes in proliferation and apoptosis underlying the aberrant persistence of follicular cysts. Free Spanish abstract: A Spanish translation of this abstract is freely available at

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“…For example, male X. borealis might produce enough estrogen via aromatization of gonadal androgens to strengthen their laryngeal synapse. As both this estrogen-driven mechanism and androgendriven differentiation of fiber type appear to be absent in X. borealis, their loss could reflect change in a common element, such as a shared and required receptor co-regulator (Feng and O'Malley, 2014). Alternatively, the laryngeal synapse of both sexes may be strong and independent of endocrine control.…”

Section: Borealis Has Lost Certain Male-specific Laryngeal Charactersmentioning

confidence: 99%

Species-specific loss of sexual dimorphism in vocal effectors accompanies vocal simplification in African clawed frogs (Xenopus)

Leininger

Kitayama

Kelley

2015

Journal of Experimental Biology

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Phylogenetic studies can reveal patterns of evolutionary change, including the gain or loss of elaborate courtship traits in males. Male African clawed frogs generally produce complex and rapid courtship vocalizations, whereas female calls are simple and slow. In a few species, however, male vocalizations are also simple and slow, suggesting loss of male-typical traits. Here, we explore features of the male vocal organ that could contribute to loss in two species with simple, slow male calls. In Xenopus boumbaensis, laryngeal morphology is more robust in males than in females. Larynges are larger, have a more complex cartilaginous morphology and contain more muscle fibers. Laryngeal muscle fibers are exclusively fasttwitch in males but are both fast-and slow-twitch in females. The laryngeal electromyogram, a measure of neuromuscular synaptic strength, shows greater potentiation in males than in females. Malespecific physiological features are shared with X. laevis, as well as with a species of the sister clade, Silurana tropicalis, and thus are likely ancestral. In X. borealis, certain aspects of laryngeal morphology and physiology are sexually monomorphic rather than dimorphic. In both sexes, laryngeal muscle fibers are of mixed-twitch type, which limits the production of muscle contractions at rapid intervals. Muscle activity potentiation and discrete tension transients resemble female rather than male X. boumbaensis. The demasculinization of these laryngeal features suggests an alteration in sensitivity to the gonadal hormones that are known to control the sexual differentiation of the larynx in other Xenopus and Silurana species.

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Nuclear receptor modulation – Role of coregulators in selective estrogen receptor modulator (SERM) actions

Cited by 48 publications

References 63 publications

Development of selective androgen receptor modulators (SARMs)

Development of selective androgen receptor modulators (SARMs)

Molecular aspects of bovine cystic ovarian disease pathogenesis

Species-specific loss of sexual dimorphism in vocal effectors accompanies vocal simplification in African clawed frogs (Xenopus)

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