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Activation of PPAR? by Rosiglitazone does not negatively impact male sex steroid hormones in diabetic rats.

ABSTRACT: Peroxisome proliferator-activated receptor gamma (PPAR?) activation decreased serum testosterone (T) in women with hyperthecosis and/or polycystic ovary syndrome and reduced the conversion of androgens to estradiol (E2) in female rats. This implies modulation of female sex steroid hormones by PPAR?. It is not clear if PPAR? modulates sex steroid hormones in diabetic males. Because PPAR? activation by thiazolidinedione increased insulin sensitivity in type 2 diabetes, understanding the long term impact of PPAR? activation on steroid sex hormones in males is critical. Our objective was to determine the effect of PPAR? activation on serum and intratesticular T, luteinizing hormone (LH), follicle stimulating hormone (FSH) and E2 concentrations in male Zucker diabetic fatty (ZDF) rats treated with the PPAR? agonist rosiglitazone (a thiazolidinedione). Treatment for eight weeks increased PPAR? mRNA and protein in the testis and elevated serum adiponectin, an adipokine marker for PPAR? activation. PPAR? activation did not alter serum or intratesticular T concentrations. In contrast, serum T level but not intratesticular T was reduced by diabetes. Neither diabetes nor PPAR? activation altered serum E2 or gonadotropins FSH and LH concentrations. The results suggest that activation of PPAR? by rosiglitazone has no negative impact on sex hormones in male ZDF rats.

SUBMITTER: Mansour M

PROVIDER: S-EPMC2696180 | biostudies-literature | 2009

REPOSITORIES: biostudies-literature

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Activation of PPARγ by Rosiglitazone does not negatively impact male sex steroid hormones in diabetic rats.

Mansour Mahmoud M Coleman Elaine E Dennis John J Akingbemi Benson B Schwartz Dean D Braden Tim T Judd Robert R Plaisance Eric E Stewart Laura Ken LK Morrison Edward E

PPAR research 20090611

Peroxisome proliferator-activated receptor gamma (PPARγ) activation decreased serum testosterone (T) in women with hyperthecosis and/or polycystic ovary syndrome and reduced the conversion of androgens to estradiol (E2) in female rats. This implies modulation of female sex steroid hormones by PPARγ. It is not clear if PPARγ modulates sex steroid hormones in diabetic males. Because PPARγ activation by thiazolidinedione increased insulin sensitivity in type 2 diabetes, understanding the long term ...[more]

PMID: 19536350

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Project description:ObjectiveSex steroid hormones may play a role in insulin resistance and glucose dysregulation. However, evidence regarding associations between early-pregnancy sex steroid hormones and hyperglycemia during pregnancy is limited. The primary objective of this study was to assess the relationships between first trimester sex steroid hormones and the subsequent development of hyperglycemia during pregnancy; with secondary evaluation of sex steroid hormones levels in mid-late pregnancy, concurrent with and subsequent to diagnosis of gestational diabetes.MethodsRetrospective analysis of a prospective pregnancy cohort study was conducted. Medically low-risk participants with no known major endocrine disorders were recruited in the first trimester of pregnancy (n=319). Sex steroid hormones in each trimester, including total testosterone, free testosterone, estrone, estradiol, and estriol, were assessed using high-performance liquid chromatography and tandem mass spectrometry. Glucose levels of the 1-hour oral glucose tolerance test and gestational diabetes diagnosis were abstracted from medical records. Multivariable linear regression models were fitted to assess the associations of individual first trimester sex steroids and glucose levels.ResultsIn adjusted models, first trimester total testosterone (β=5.24, 95% CI: 0.01, 10.46, p=0.05) and free testosterone (β=5.98, 95% CI: 0.97, 10.98, p=0.02) were positively associated with subsequent glucose concentrations and gestational diabetes diagnosis (total testosterone: OR=3.63, 95% CI: 1.50, 8.78; free testosterone: OR=3.69; 95% CI: 1.56, 8.73). First trimester estrone was also positively associated with gestational diabetes (OR=3.66, 95% CI: 1.56, 8.55). In mid-late pregnancy, pregnant people with gestational diabetes had lower total testosterone levels (β=-0.19, 95% CI: -0.36, -0.02) after adjustment for first trimester total testosterone.ConclusionEarly-pregnancy sex steroid hormones, including total testosterone, free testosterone, and estrone, were positively associated with glucose levels and gestational diabetes in mid-late pregnancy. These hormones may serve as early predictors of gestational diabetes in combination with other risk factors.

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Activation of PPAR? by Rosiglitazone does not negatively impact male sex steroid hormones in diabetic rats.

Publications

Activation of PPARγ by Rosiglitazone does not negatively impact male sex steroid hormones in diabetic rats.

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