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1.
Clin Chim Acta ; 547: 117456, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37385468

RESUMO

BACKGROUND: Androgenetic alopecia (AGA) is treated by 5α-reductase inhibitors (5ARI) such as finasteride and dutasteride, which are widely used as therapeutic agents. However, their pharmacokinetics in target organs (scalp and hair follicles) have not yet been investigated. PURPOSE: To confirm the effective action of finasteride and dutasteride in the hair follicle tissues, we developed a method to measure these concentrations in hair. RESULTS: Compared to the non-detection (N.D.) group, the dihydrotestosterone (DHT) concentrations decreased significantly in both the finasteride and dutasteride groups. The dutasteride group showed significantly lower DHT concentrations among all groups. CONCLUSIONS: Measurement of finasteride, dutasteride, and DHT concentrations in hair would aid in evaluating the drug pharmacokinetics and its therapeutic effects on AGA patients.


Assuntos
Di-Hidrotestosterona , Finasterida , Humanos , Finasterida/efeitos adversos , Dutasterida/efeitos adversos , Alopecia/tratamento farmacológico , Alopecia/induzido quimicamente , Alopecia/diagnóstico , Cabelo
2.
Eur J Endocrinol ; 187(6): K39-K45, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36691941

RESUMO

SIGNIFICANCE STATEMENT: Due to its rarity, biochemical and histologic characteristics of androgen and glucocorticoid co-secreting adrenocortical adenomas are largely unknown. Herein, we report a case of adrenocortical adenoma that caused marked hyperandrogenemia and mild autonomous cortisol secretion. In this study, we investigated serum steroid profiles using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and histologic characteristics of the resected tumor. LC-MS/MS revealed highly elevated levels of 11-oxygenated androgens which have not been well studied in adrenal tumors. The expression patterns of steroidogenic enzymes determined by immunohistochemistry supported the results of steroid profiling and suggested the capacity of the tumor cells to produce 11-oxygenated androgens. Measurement of 11-oxygenated steroids should facilitate a better understanding of androgen-producing adrenocortical neoplasms.


Assuntos
Neoplasias do Córtex Suprarrenal , Adenoma Adrenocortical , Humanos , Adenoma Adrenocortical/metabolismo , Glucocorticoides/metabolismo , Androgênios , Cromatografia Líquida , Hidrocortisona , Espectrometria de Massas em Tandem , Neoplasias do Córtex Suprarrenal/patologia , Esteroides , Hormônio Adrenocorticotrópico
3.
Plant Cell Physiol ; 57(12): 2497-2509, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27986914

RESUMO

Soybean (Glycine max) accumulates several prenylated isoflavonoid phytoalexins, collectively referred to as glyceollins. Glyceollins (I, II, III, IV and V) possess modified pterocarpan skeletons with C5 moieties from dimethylallyl diphosphate, and they are commonly produced from (6aS, 11aS)-3,9,6a-trihydroxypterocarpan [(-)-glycinol]. The metabolic fate of (-)-glycinol is determined by the enzymatic introduction of a dimethylallyl group into C-4 or C-2, which is reportedly catalyzed by regiospecific prenyltransferases (PTs). 4-Dimethylallyl (-)-glycinol and 2-dimethylallyl (-)-glycinol are precursors of glyceollin I and other glyceollins, respectively. Although multiple genes encoding (-)-glycinol biosynthetic enzymes have been identified, those involved in the later steps of glyceollin formation mostly remain unidentified, except for (-)-glycinol 4-dimethylallyltransferase (G4DT), which is involved in glyceollin I biosynthesis. In this study, we identified four genes that encode isoflavonoid PTs, including (-)-glycinol 2-dimethylallyltransferase (G2DT), using homology-based in silico screening and biochemical characterization in yeast expression systems. Transcript analyses illustrated that changes in G2DT gene expression were correlated with the induction of glyceollins II, III, IV and V in elicitor-treated soybean cells and leaves, suggesting its involvement in glyceollin biosynthesis. Moreover, the genomic signatures of these PT genes revealed that G4DT and G2DT are paralogs derived from whole-genome duplications of the soybean genome, whereas other PT genes [isoflavone dimethylallyltransferase 1 (IDT1) and IDT2] were derived via local gene duplication on soybean chromosome 11.


Assuntos
Dimetilaliltranstransferase/genética , Flavonóis/metabolismo , Genoma de Planta/genética , Glycine max/enzimologia , Isoflavonas/metabolismo , Pterocarpanos/metabolismo , Dimetilaliltranstransferase/metabolismo , Flavonóis/química , Duplicação Gênica , Ordem dos Genes , Isoflavonas/química , Filogenia , Folhas de Planta/química , Folhas de Planta/enzimologia , Folhas de Planta/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Pterocarpanos/química , Sesquiterpenos/química , Sesquiterpenos/metabolismo , Glycine max/química , Glycine max/genética , Fitoalexinas
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