Disease relevance of UBL4A

• Y-negative XX males belong to the same clinical spectrum as XX true hermaphrodites, and gonadal dysgenesis in some XY females may be due to sporadic or familial mutations of GDX [1].

High impact information on UBL4A

• Intratissular dihydrotestosterone (-59 to -99%), estradiol (-31 to -53%), and androsterone-glucuronide (-28 to -85%) concentrations also decreased after GDX [2].
• Serum concentrations of dehydroepiandrosterone, dehydroepiandrosterone sulfate (DHEA-S), and androstenediol remained stable after GDX [2].
• To better understand the opposite effects of GDX and CAB on lipid metabolism, we have compared the changes in plasma lipoproteins, mesenteric fat metabolism, as well as serum and intratissular sex steroid concentrations in intact, GDX, and GDX+FLU [GDX male cynomolgus monkeys treated for 3 months with flutamide (FLU)] [2].
• GDX induced significant increases in plasma low-density lipoprotein (LDL) (+78%) and high-density lipoprotein (+34%) cholesterol as well as in LDL-apoB (+58%) and high-density lipoprotein-apoAI (+32%) [2].
• Serum androstenedione (-40%), testo (-97%), dihydrotestosterone (-89%), androsterone-glucuronide (-75%), and androstane-3alpha,17beta-diol-glucuronide (-80%) levels decreased similarly in both GDX and GDX+FLU animals [2].

Biological context of UBL4A

• The findings in most cases are consistent with the hypothesis of homologous gonad-determining genes, GDX and GDY, carried by the X and Y chromosomes respectively [1].
• The depletion of endogenous androgens by GDX significantly augmented lesion severity, consistent with the hypothesis that androgens are involved in maintaining cell viability [3].
• It is postulated that in sporadic or familial XX true hermaphrodites one of the GDX loci escapes X-inactivation because of mutation or chromosomal rearrangement, resulting in mosaicism for testis and ovary-determining cell lines in somatic cells [1].
• We find that the five human X-linked genes (G6PD, GDX, F9, AR and MCF2) map to the echidna X1 chromosome in locations equivalent to those on the platypus X [4].
• The data indicate that GDX enhances gene expression of both TH and NET [5].

Anatomical context of UBL4A

• INTERVENTION: The RNFL thickness was assessed with a scanning laser polarimeter (Nerve Fiber Analyzer GDX, Laser Diagnostic Technologies Inc., San Diego, CA) [6].
• To investigate how gonadal steroids influence noradrenergic neuronal activities in the locus coeruleus (LC), mRNA levels of tyrosine hydroxylase (TH) and NE transporter (NET), two key factors regulating NE synthesis and uptake, were compared 3 weeks after gonadectomy (GDX) [5].
• Second, we hypothesized that, if androgens' effects are due in part to actions of 3alpha-diol in the hippocampus, then systemic or intrahippocampal administration of 3alpha-diol should significantly enhance cognitive performance of GDX male rats [7].

Associations of UBL4A with chemical compounds

• Since gonadectomy (GDX) attenuates LTF in male rats, we tested the hypotheses that: (1) testosterone replenishment restores LTF in gonadectomized male rats, and (2) that the conversion of testosterone to oestradiol (under the influence of aromatase) is required for these effects [8].
• Importantly, DHT hormone replacement in GDX rats significantly attenuated kainate-induced neuron loss in CA2/3, suggesting direct androgen neuroprotection [3].
• Adult male rats were maintained in the following conditions: i) gonadectomized (GDX) to deplete endogenous androgens, ii) GDX+replacement with dihydrotestosterone (DHT) the active and non-aromatizable testosterone metabolite, iii) sham-GDX [3].
• Three weeks after gonadectomy (GDX) or sham-surgery (INT), animals were randomly divided into groups to be left in the home cage as controls (HC) or to be exposed to Sham (S) or Formalin (F) stimuli (s.c. formalin injection, 50 microl, 5%, in the dorsal hind paw) in the subsequent 2 weeks (Trial 1; Trial 2) [9].
• In those studies, AR mRNA levels were up-regulated after 1 day of treatment with exogenous TP in FMN of gonadectomized (GDX) males and after 7 days in FMN of intact females, with no effects in GDX females [10].

Analytical, diagnostic and therapeutic context of UBL4A

• In men, orchiectomy (GDX) produces an atherogenic lipid profile, whereas combined androgen blockade (CAB) induces a favorable lipid pattern [2].
• Semi-quantitative RT-PCR revealed a significant elevation of FSHbeta, but not LHbeta, in mature male R. pipiens 21 days after gonadectomy (GDX) [11].

References