Age, body mass index, and serum level of DHEA-S can predict glucocorticoid receptor function in women with polycystic ovary syndrome

Abstract

Glucocorticoid receptor (GR) transduces the glucocorticoid (GC) signal that could lead to metabolic derangements depending on the tissue responsiveness to GC. We aimed to investigate possible causative relation of the GR functional properties in peripheral blood mononuclear cells of women with polycystic ovary syndrome (PCOS), with their clinical and biochemical characteristics. Thirty women with PCOS [mean age: 26.5 ± 5.1 years, mean body mass index (BMI) 24.5 ± 5 kg/m(2)], and thirty respective controls were analyzed for the number of GR sites per cell (B (max)), apparent equilibrium dissociation constant (K (d)), and binding potency (GR potency). A strong association between B (max) and K (d) (r = 0.70, P < 0.0001), and GR potency with age (r = 0.49, P = 0.009) was observed in PCOS women. The multiple regression analyses within the PCOS group revealed that independent predictors for K (d) were BMI, total cholesterol, and dehydroepiandrosterone-sulfate (DHEA-S) (r = 0.58, P = 0.038), while for GR potency (r = 0.687, P = 0.013) were age, BMI, DHEA-S, and basal cortisol concentration. The results suggest that PCOS pathophysiology may be related to alterations of a cross stalk between glucocorticoid signaling, age, and metabolic parameters. These findings should be further explored in studies on the role of GR in PCOS-related metabolic derangements.

Overview of the detection methods for equilibrium dissociation constant KD of drug-receptor interaction

“…As shown in Table 1 , RBA can be used to determine the affinity constant, dissociation constant and the number of binding receptors [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] , [30] , [31] , [32] , [33] , [34] . The key condition of receptor binding experiments is to prepare an excellent radioligand.…”

“…The ability to prepare novel and selective radioligands facilitates the study of drug-receptor interaction, and RBA provides an effective tool for studying the mechanisms of drugs at molecular level [37] , [38] . A variety of receptor materials can be used in the RBA method, such as the cell membrane obtained from cell and tissue [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] , intact cells [29] , [30] , tissue slice [31] , [32] , [33] , [34] , and engineered protein samples [38] , [39] .…”

Identification of new biomarker candidates for glucocorticoid induced insulin resistance using literature mining

“…Also a study by Macut et al . suggested that alterations of a cross-talk between glucocorticoid signaling and metabolic parameters, is related to PCOS pathophysiology [42]. …”

MECHANISMS IN ENDOCRINOLOGY: Aging and anti-aging: a Combo-Endocrinology overview

“…It is shown that an increased concentration of DHEAS in women is associated with a higher prevalence of cardiovascular disease. A possible explanation is that elevated levels of DHEA and DHEAS, as is the case in women with hyperandrogenism, can act as the activators of translocation of the glucocorticoid receptor (GR) in the nucleus, which lead to a change in the functional characteristics of GR (128).…”