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. 2004 Jul;63(7):809–816. doi: 10.1136/ard.2003.011619

Possible role of leptin in hypoandrogenicity in patients with systemic lupus erythematosus and rheumatoid arthritis

P Harle 1, G Pongratz 1, C Weidler 1, R Buttner 1, J Scholmerich 1, R Straub 1
PMCID: PMC1755074  PMID: 15194576

Abstract

Background: Hypoandrogenicity is common in obesity and in chronic inflammatory diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Adrenal androgens such as androstenedione (ASD) and dehydroepiandrosterone (DHEA) sulphate are low, which partly depends on the influence of TNF in chronic inflammatory diseases. Leptin is stimulated by TNF and is associated with hypoandrogenicity in non-inflammatory conditions.

Objective: To study the interrelation between serum levels of leptin and adrenal steroids in SLE and RA.

Methods: In a retrospective study, serum levels of leptin, ASD, DHEA, and 17-hydroxyprogesterone (17OHP) were measured by ELISA, and serum levels of cortisol by radioimmunoassay in 30 patients with RA, 32 with SLE, and 54 healthy control subjects (HS).

Results: In SLE and RA but not HS, serum levels of ASD correlated negatively with serum levels of leptin (p<0.01) independently of prior prednisolone treatment in patients with SLE (p = 0.013) and tended to be independent of prednisolone in patients with RA (p = 0.067). In a partial correlation analysis, this interrelation remained significant after controlling for daily prednisolone dose in both patient groups. In both patient groups, serum leptin levels correlated negatively with the molar ratio of serum ASD/serum cortisol and serum ASD/serum 17OHP, and positively with the molar ratio of serum DHEA/serum ASD.

Conclusions: The negative correlation of serum leptin and ASD or, particularly, ASD/17OHP, together with its known anti-androgenic effects indicate that leptin is also involved in hypoandrogenicity in patients with SLE and RA. Leptin may be an important link between chronic inflammation and the hypoandrogenic state.

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Figure 1.

Figure 1

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 Pathways of steroidogenesis. A line with a bar at the end demonstrates that the respective mediator inhibits the enzyme step (tumour necrosis factor (TNF)). Abbreviations: 3ßHSD, 3ß-hydroxysteroid dehydrogenase; 11ßHSD I and II; 11ß-hydroxysteroid dehydrogenase types I and II; DHEA, dehydroepiandrosterone; DHEAS, DHEA sulphate; DST, DHEA sulphotransferase; IL6, interleukin 6; P450c11, 11ß-hydroxylase; P450c17, 17α-hydroxylase and 17/20-lyase (double enzyme step); P450c21, 21α-hydroxylase; P450scc, side chain cleavage enzyme; ST, DHEAS sulphatase; StAR, steroidogenic acute regulatory protein; TNF, tumour necrosis factor.

Figure 2.

Figure 2

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 Interrelation between serum levels of ASD and leptin in patients with SLE, RA, and HS. Open symbols (broken line) stand for patients with prior prednisolone treatment whereas black symbols (solid line) represent patients without prior prednisolone treatment. The linear regression lines, the Spearman rank correlation coefficients (RRank) and the p values are given in the panels. Direct comparison of patients with SLE, RA, and HS is not meaningful because of the unknown body mass index (take notice of the different scales).

Figure 3.

Figure 3

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 Interrelation between the molar ratio of serum ASD/serum cortisol and leptin in all patients with SLE, RA, and HS. In both disease groups, patients with and without prior prednisolone treatment were included. The linear regression line, the Spearman rank correlation coefficient (RRank) and the p value are given in the panels. Direct comparison of patients with SLE, RA, and HS is not meaningful because of the unknown body mass index (take notice of different scales).

Figure 4.

Figure 4

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 Interrelation between the molar ratio of serum ASD/serum 17OHP and leptin in all patients with SLE, RA, and HS. In both disease groups, patients with and without prior prednisolone treatment were included. The linear regression line, the Spearman rank correlation coefficient (RRank) and the p value are given in the panels. Direct comparison of patients with SLE, RA, and HS is not meaningful because of the unknown body mass index (take notice of the different scales).

Figure 5.

Figure 5

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 Interrelation between the molar ratio of serum (DHEA)/serum ASD and serum leptin in all patients with SLE, RA, and HS. In both disease groups, patients with and without prior prednisolone treatment were included. The linear regression line, the Spearman rank correlation coefficient (RRank), and the p value are given in the panels. Direct comparison of patients with SLE, RA, and HS is not meaningful because of the unknown body mass index (take notice of different scales).

Selected References

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