Intramuscular antagonism of the G-protein coupled estrogen receptor 1 partially affects dimorphic characteristics of the syrinx, but is ineffective within the neural song circuit of zebra finches
androgen receptor; behavior; brain; control nuclei; Drug delivery; estradiol; Estrogen receptor; expression; GPER1 antagonist; gpr30; growth; Sexual dimorphism; sexual-differentiation; Songbird; Syrinx; system
Within the zebra finch song system, robust sex differences exist that enable singing behavior in males, but not females. Estradiol is a potent contributor to this process, but how and through which receptor(s) it acts is not clear. Historically, pharmacological manipulations of nuclear estrogen receptors have yielded conflicting results possibly due to method of drug delivery. More recently, the membrane bound G-protein coupled estrogen receptor 1 (GPER1) has also been identified as a potential candidate, but its function has not been fully described. To further investigate the role of GPER1, and the importance of the route of drug administration, a specific antagonist (G-15) was intramuscularly administered to zebra finches for 25 days, starting on the day of hatching. G-15 significantly decreased muscle fiber sizes of ventralis and dorsalis in the syrinx of males only. Dimorphic characteristics of the neural song system were unaffected by this manipulation in either sex. These results contrast with a study in which G-15 was intracranially delivered. In males, select song nuclei were decreased in volume, and in females, syrinx muscle fiber size was increased. Together, these results support the hypothesis that estrogens acting through GPER1 influence dimorphic development of the song system, and that method of drug administration is important in this species.
Tehrani Mahtab Attarhaie; Veney Sean L
General and Comparative Endocrinology
2020
2020-07-01
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
journalArticle
<a href="http://doi.org/10.1016/j.ygcen.2020.113492" target="_blank" rel="noreferrer noopener">10.1016/j.ygcen.2020.113492</a>
Similarities and Differences between Two Modes of Antagonism of the Thyroid Hormone Receptor
androgen receptor; Biochemistry & Molecular Biology; coactivator binding; estrogen receptor; gene-expression; growth-hormone; hepatoma-cell line; hepg2; liver; nuclear receptor; small-molecule inhibitors
Thyroid hormone (T3) mediates diverse physiological functions including growth, differentiation, and energy homeostasis through the thyroid hormone receptors (TR). The TR binds DNA at specific recognition sequences in the promoter regions of their target genes known as the thyroid, hormone response elements (TREs). Gene expression at TREs regulated by TRs is mediated by coregulator recruitment to the DNA bound receptor. This TR-coregulator interaction controls transcription of target genes by multiple mechanisms including covalent histone modifications and chromatin remodeling. Our previous studies identified a beta-aminoketone as a potent inhibitor of the TR-coactivator interaction. We describe here the activity of one of these inhibitors in modulating effects of T3 signaling in comparison to an established ligand-competitive inhibitor of TR, NH-3. The beta-aminoketone was found to reverse thyroid hormone induced gene expression by inhibiting coactivator recruitment at target gene promoters, thereby regulating downstream effects of thyroid hormone. While mimicking the downstream effects of NH-3 at the molecular level, the beta-aminoketone affects only a subset of the thyroid responsive signaling network. Thus antagonists directed to the coregulator binding site have distinct pharmacological properties relative to ligand-based antagonists and may provide complementary activity in vivo.
Sadana P; Hwang J Y; Attia R R; Arnold L A; Neale G; Guy R K
Acs Chemical Biology
2011
2011-10
Journal Article
<a href="http://doi.org/10.1021/cb200092v" target="_blank" rel="noreferrer noopener">10.1021/cb200092v</a>
Estrogen receptors in the spinal card, sensory ganglia, and pelvic autonomic ganglia
beta messenger-rna; central-nervous-system; cervical-ganglion; dorsal root ganglia; dorsal-root ganglion; estradiol-concentrating cells; estrogen; estrogen receptor; galanin-like immunoreactivity; ganglia; gene-related peptide; neurotransmitters; noradrenaline-containing nerves; parasympathetic; pelvic autonomic; preganglionic neurons; pregnancy; superior; vasoactive intestinal polypeptide
Papka R E; Mowa C N
International Review of Cytology - a Survey of Cell Biology, Vol 231
2003
2003
Book Section
<a href="http://doi.org/10.1016/s0074-7696(03)31003-4" target="_blank" rel="noreferrer noopener">10.1016/s0074-7696(03)31003-4</a>