Androsterone sulfate: physiology and clinical significance in hirsute women.

Abstract

Androsterone sulfate (Andros-S) is the most abundant 5 alpha-reduced androgen metabolite in serum. To determine whether this steroid could serve as a marker of 5 alpha-reductase activity, we developed a specific RIA, using tritiated Andros-S to assess procedural losses. Baseline serum Andros-S levels (mumol/L; mean +/- SEM) in 14 hirsute women (3.0 +/- 0.4) were not reduced by ovarian suppression with leuprolide (3.0 +/- 0.3), but were decreased by 79% with combined ovarian and adrenal suppression with leuprolide and dexamethasone. The mean Andros-S level in polycystic ovarian syndrome (3.2 +/- 0.4) and in idiopathic hirsutism (3.5 +/- 0.5) was not significantly different from levels in normal women (3.0 +/- 0.5), but were significantly greater than levels in obese women (1.7 +/- 0.3; P < 0.05). The serum concentrations of Andros-S were about 10-fold greater than those of androsterone glucuronide and 100-fold greater than those of androstanediol glucuronide. Serum Andros-S concentrations correlated strongly with dehydroepiandrosterone sulfate (R = 0.59; P < 0.001) and to a lesser degree with androstanediol glucuronide and androsterone glucuronide (R = 0.28 and 0.49, respectively). There was a weak correlation with androstenedione levels and the androstenedione response to ACTH (R = 0.38 and 0.34, respectively), and no significant correlation with serum testosterone (R = 0.19). The ratio of any of the 5 alpha-reduced products (Andros-S, androstanediol glucuronide, and androsterone glucuronide) to precursors (androstenedione and testosterone) was not increased in hirsute women, suggesting that these women did not have a generalized increase in 5 alpha-reductase activity. In conclusion, these results confirm that Andros-S is the most abundant 5 alpha-reduced androgen metabolite in serum. It is primarily, if not exclusively, of adrenal origin in hirsute women. The fact that its levels were not elevated in hirsutism, although those of other adrenal androgens and androgen metabolites (androstanediol glucuronide and androsterone glucuronide) were, suggests that variations in sulfotransferase activity or metabolic clearance of Andros-S may be important determinants of serum Andros-S levels. Although Andros-S may be a marker of systemic 5 alpha-reductase activity, there was no evidence of a generalized increase in 5 alpha-reductase activity in hirsute women. Andros-S is therefore not recommended as a marker of either adrenal androgen production or of hirsutism.

Identifying Androsterone (ADT) as a Cognate Substrate for Human Dehydroepiandrosterone Sulfotransferase (DHEA-ST) Important for Steroid Homeostasis

“…Based on the measurements of steroid level and correlations among steroids in serum, the two sulfated steroids, ADTS and DHEAS were significantly correlated (r ϭ 0.59) (12). This is even more interesting if we consider DHEAS the major androgen precursor and ADTS one of the main androgen metabolites in view of steroid homeostasis.…”

“…In the placenta, the hydroxylated DHEAS is desulfated and aromatized to form estriol, which increases uteroplacental blood flow, and then is secreted into the maternal circulation (11). Androsterone sulfate (ADTS) is the most abundant circulating 5␣-reduced androgen metabolite in serum (12), while DHEAS is the major precursor for the active steroid hormones. A fraction of dehydroepiandrosterone (DHEA) is metabolized in liver, resulting in androstenedione and the double bond of the latter compound is reduced by 5␣-reductase, giving rise to 5␣-and 5␤-androstanedione.…”

Papel dos Androgênios Adrenais e Periféricos na Modulação dos Níveis da Globulina Ligadora dos Hormônios Sexuais na Pubarca Precoce

“…Logo, a PP parece ser uma manifestação de variável expressão clínica em resposta aos androgênios. Embora a DHT ser considerada um androgênio ativo na pele, seus níveis não se correlacionam bem com o hirsutismo, presumivelmente porque a DHT é rapidamente convertida para o 3α-diolG (11,12). Este último vem se tornando alvo de grande interesse para a investigação do hiperandrogenismo em adultos, principalmente quando os níveis dos androgênios são normais (13).…”

“…Os androgênios adrenais têm sido considerados os principais precursores do 3α-diolG em mulheres normais e hirsutas. Alguns estudos demostram que a T e a DHT são responsáveis por mais de 50% do 3α-diolG plasmático, outros demonstram que a A pode ser sua principal fonte, mas existem poucos estudos que suportam a hipótese de que o SDHEA possa ser um importante precursor na mulher adulta (11,12).…”

A theoretical study on the characteristics of the intermolecular interactions in the active site of human androsterone sulphotransferase: DFT calculations of NQR and NMR parameters and QTAIM analysis

“…Free ADT structure is shown in Figure 1 [8]. Androsterone sulfate (ADTS) is the most abundant circulating 5α-reduced androgen metabolite in serum [9]. Moreover, the binary complex crystal structures of enzyme human SULT2A1 have been reported in the presence of DHEA (SULT2A1/DHEA, PDB ID: 1J99) [10], as well as in the presence of 3'-phosphoadenosine 5'-phosphate (PAP) and in the absence of the substrate (SULT2A3, PDB ID: 1EFH) [11].…”