Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042755 (masculinization)
 2,562 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Testosterone-treated calf thymocytes produce increased amounts of proteins, termed lipokinins, that stimulate phospholipase A2 from snake venom and mammalian tissue. The induction of these proteins by testosterone is blocked by cycloheximide and, thus, requires new protein synthesis. These proteins activate phospholipase A2 stoichiometrically. They are inactivated by boiling, trypsin or alkaline phosphatase but not by deoxyribonuclease or ribonuclease. Lipokinins significantly repair the failure of masculinization in the Tfm mouse with an X-linked deficiency of androgen-receptor. Thus, the post-receptor effects of testosterone on embryonic genitalia may be mediated through stimulation of phospholipase A2 by lipokinins. Moreover, lipokinins may be involved as stimulators of the arachidonic acid cascade, as lipocortins are inhibitors.
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PMID:John Lattimer lecture. Lipokinins: novel phospholipase A2 activators mediate testosterone effects on embryonic genitalia. 318 94

Androgen receptors were identified in the cytosol from ovaries of juvenile coho salmon, Oncorhynchus kisutch. The binding for the synthetic androgen mibolerone was specific and saturable (Kd = 0.32 +/- 0.02 nM; Bmax = 15.31 +/- 4.31 fmol/mg protein). Bound [3H]mibolerone was much higher in ovarian cytosol than in cytosolic extracts from heart, liver, and muscle. [3H]mibolerone specific binding was 50% lower in the plasma than in the ovarian cytosolic extracts. [3H]mibolerone binding was displaced most effectively by those 17 alpha-methylated synthetic androgens (mibolerone, methyltestosterone, methylandrostanolone) that can induce functional masculinization in fish. The naturally occurring androgens 11-ketotestosterone and 5 alpha-dihydrotestosterone both displaced [3H]mibolerone binding, but they were 10- to 100-fold less effective than the 17 alpha-methylated androgens. Testosterone, 11 beta-hydroxyandrostenedione, estradiol, progesterone, and 17 alpha,20 beta-dihydroxyprogesterone were not potent competitors. [3H]mibolerone specific binding was reduced after preincubation with trypsin. About 25% of the binding in the cytosolic extract had DNA binding affinity under experimental conditions. The characteristics of this androgen binding site are consistent with a model of receptor-mediated steroid-induced sex inversion.
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PMID:Binding characteristics of an androgen receptor in the ovaries of coho salmon, Oncorhynchus kisutch. 782 77

This study aimed to report a rare case of intermittent azoospermia and ring-like small supernumerary marker chromosomes (sSMCs). An infertile man was diagnosed with azoospermia presenting a normal male phenotype with complete masculinization. Karyotyping and polymerase chain reaction (PCR) were used to detect 16 sequence-tagged sites on the AZF subregions of the Y chromosome, and 115 candidate genes were screened for mutations. Mutations included single nucleotide variations, insertions, and deletions. Metaphase chromosomes were studied by standard trypsin-Giemsa banding; fluorescent in situ hybridization and PCR were performed to analyze specific Y chromosome regions; gene mutations were detected. Chromosomal analysis detected 117 metaphase cells; a mosaicism with marker 1 and marker 2 sSMCs in 2 metaphase cells (47, X, +mar1x2 karyotype), a mosaicism with marker 2 sSMCs in 14 metaphase cells (46, X, +mar2 karyotype), and a mosaicism with marker 1 sSMCs in 76 metaphase cells (46, X, +mar1 karyotype), coexisting with a 45,X cell line in the remaining 25 metaphase cells. PCR analysis showed the sY160 heterochromosome on the AZFc subregion was absent. Next-generation sequencing identified an asthenozoospermia-specific mutation in GAPDHS (rs2293681), and Sanger sequencing verified this mutation. This gene encodes a protein belonging to the glyceraldehyde-3-phosphate dehydrogenase family of enzymes that play an important role in carbohydrate metabolism. Like its somatic cell counterpart, this sperm-specific enzyme functions in a nicotinamide adenine dinucleotide-dependent manner to remove hydrogen and add phosphate to glyceraldehyde 3-phosphate to form 1,3-diphosphoglycerate. During spermiogenesis, this enzyme may play an important role in regulating the switch between different energy-producing pathways, and it is required for sperm motility and male fertility. A mosaic 46, X, +mar1[76]/45, X[25]/46, X, +mar2[14]/47, X, +mar1x2[2] karyotype could be the main explanation for the azoospermia/severe oligospermia, while the likely pathogenic GAPDHS intron mutation may contribute to the symptom of immotile sperms detected in the semen analysis.
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PMID:Mosaic Ring-like Small Supernumerary Marker Chromosome and Gene Mutation in a Male With Intermittent Azoospermia: A Rare Case Report. 3232 48