Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Estrogen-induced signaling mediated by estrogen receptors (ERs) is also affected by aberrant ERs that act as constitutively active or dominant negative modulators. Variant ERs can contribute to carcinogenesis and to the loss of estrogen responsiveness, rendering antiestrogen therapy ineffective. Determining target gene response during co-synthesis of different ER species is difficult, because dimers formed in the presence of more than one ER species are a heterogenous population of homo- or heterodimers. We engineered a homofusion ERalpha as a prototype single-chain receptor by genetically conjugating two ER monomers into a covalently fused single-chain protein to obtain a homogeneous population. This permits analysis of symmetrical or asymmetrical mutations that simulate variant homo- and heterodimers. Although a monomer, the homofusion receptor exhibited similar biochemical and functional properties to the dimeric ERalpha. We used activation function-2 (AF2) defective mutants as a model in either one or both receptor domains for a dominant-negative phenotype by suppressing the reporter activity induced by the WT receptor. When co-expressed with ERalpha, the fusion variant deficient in both AF2 functions suppressed the reporter activity effectively induced by ERalpha. These results show the utility of fusion receptors as models for generation of receptor-based agonists and antagonists.
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PMID:Fusion estrogen receptor proteins: toward the development of receptor-based agonists and antagonists. 1151 59

Mosaicism 45X/47XXX is a sporadic form of ovarian dysgenesis. Many of the cases previously described were characterized by a variable phenotype expression. We here report the case of a 33-yr-old woman with recent secondary amenorrhea, weight loss and breast regression. Her menarche had occurred at the age of 11 yr and 6 months and her menstrual cycles had been regular until the age of 28; then, oligomenorrhea and hypertricosis developed. A pelvic ultrasound showed enlarged polycystic-like ovaries and normal uterus. She was treated with ethynil-estradiol and cyproterone acetate for one year. At the age of 31 yr, she underwent a pelvic ultrasound--which revealed normal volume of the ovaries--and hormonal assays including FSH (69 UI/l), LH (113 UI/l), 17beta-estradiol (88 pg/ml), plasma androgens and cortisol levels within normal ranges. No organ-specific autoantibodies toward ovaries, steroid-producing cells or adrenals were found. At the age of 33 yr, there was ultrasound evidence of streak-like ovaries. The patient's height was 145 cm and her weight 45 kg. She had normal female external genitalia, abnormal upper-to-lower body segment ratio, webbed neck, low posterior hair line, cubitus valgus, short and asymmetrical 4th metacarpi, hallux with lateral deviation and moderate scoliosis. No increase in ovarian steroids were found after GnRH-analogue triptorelin (0,1 mg sc) administration. The karyotype analysis on peripheral blood lymphocytes showed a mosaic 45X (90% cells) and 47XXX (10% cells). Diagnostic pelviscopy confirmed streak gonads. Chronic lymphocytic thyroiditis was diagnosed but no cardiovascular or kidney abnormalities were found. A neuro-psychological evaluation revealed emotional and social immaturity, disorders in motorial coordination, visual-spatial organization, as well as reading difficulties and impaired complex phrase construction. The presence of several somatic features of Turner's syndrome, neuro-psychological disorders and an interesting natural history probably depended on the quantitative proportion of 45X to 47XXX cell-lines in different tissues and organs. Estrogen and progestin replacement therapy led to weight gain, re-appearance of secondary sexual characteristics and a mild improvement in mental equilibrium.
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PMID:Turner's syndrome mosaicism 45X/47XXX: an interesting natural history. 1176 52

Estrogen affects female sexual behavior, analgesia, and micturition in mammals. One of the possible sites at which estrogen might exert its effect on these functions is the periaqueductal gray (PAG). The PAG is involved in each of these functions, it receives sensory input relevant to these functions from the lumbosacral cord, and contains estrogen receptor-alpha immunoreactive (ER-alpha IR) neurons. The present light (LM) and electron microscopic (EM) study seeks to determine whether there are monosynaptic projections from the lumbosacral cord to ER-alpha IR neurons in the PAG of the female rhesus monkey. Tracer was injected into the lumbosacral cord to visualize the lumbosacral-PAG projection, and the distribution of ER-alpha IR neurons in the PAG was studied immunohistochemically. The medial part of the ventrolateral caudal PAG received the densest projection from the lumbosacral cord. Another prominent projection was found in the lateral PAG at the intercollicular level. Although ER-alpha IR neurons were widely distributed throughout the PAG, approximately 40% of ER-alpha IR PAG neurons were located as a distinct cluster in the medial portion of the ventrolateral, caudal PAG. Double labeling experiments showed that the location of this cluster precisely overlapped with the densest lumbosacral-PAG projection. EM revealed that axons from the lumbosacral cord made asymmetrical synaptic contacts with unlabeled dendrites and ER-alpha IR neuronal somata in the ventrolateral PAG. It is concluded that there exists a specific, monosynaptic pathway from lumbosacral neurons to ER-alpha expressing PAG neurons in the rhesus monkey. This pathway might be involved in the mechanisms of analgesia, blood pressure, mating behavior, and micturition.
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PMID:Estrogen receptor-alpha immunoreactive neurons in the ventrolateral periaqueductal gray receive monosynaptic input from the lumbosacral cord in the rhesus monkey. 1179 45