Effects of dehydroepiandrosterone on ovarian cystogenesis and immune function

Luchetti, Carolina Griselda; Solano, María Emilia; Sander, Valeria Analía; Arcos, Marı́a Laura Barreiro; Gonzalez, Claudio; Girolamo, Guillermo Di; Chiocchio, Sara R.; Cremaschi, Graciela; Motta, Alicia Beatriz

doi:10.1016/j.jri.2004.04.002

Cited by 92 publications

(145 citation statements)

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“…It has been reported that hyperandrogenism leads to abnormal length of estrus cycles and anovulation in rats (Lee et al 1991, Henmi et al 2001 and high rates of recurrent miscarriages in early pregnant women with PCOS (Glueck et al 2002). In previous studies, we have reported that hyperandrogenization of prepuberal BALB/c mice by treatment with DHEA induces endocrine and immune disturbances in mouse ovarian tissue (Luchetti et al 2004 and embryo resorption of early pregnant mice (Sander et al 2005. The first aim of the present study was to assess the mechanisms by which hyperandrogenization affects the lifespan of CL.…”

Section: Introductionmentioning

confidence: 66%

“…The dose of DHEA injected was that previously used by Lee et al (1991Lee et al ( , 1998, Henmi et al (2001), Luchetti et al (2004), Sander et al (2005Sander et al ( , 2006, Elia et al (2006) and Solano et al (2006) and ensure a hyperandrogenized status. The dose of metformin administered was ensured to that used in the treatment of women with PCOS.…”

Section: Experimental Designmentioning

confidence: 99%

“…We evaluated serum concentration of P and E 2 by specific RIA as described previously (Luchetti et al 2004). Both antisera, which were highly specific, were kindly provided by Dr G D Niswender (Colorado State University, Fort Collins, CO, USA).…”

Section: Progesterone and E 2 Riamentioning

confidence: 99%

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Effect of DHEA and metformin on corpus luteum in mice

Sander¹,

Facorro²,

Piehl³

et al. 2009

Reproduction

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We evaluated the effect of hyperandrogenism in ovaries with functional and regressing corpora lutea (CL) and the action of metformin in preventing these possible alterations using a mouse model. To obtain a CL functional for 9G1 days, immature female mice of the BALB/c strain were injected i.p. with 10 IU/mouse of pregnant mare's serum gonadotropin (PMSG). DHEA (60 mg/kg body weight s.c., 24 and 48 h prior to kill) decreased both serum progesterone (P) and estradiol (E 2 ) levels and increased the activity of superoxide dismutase (SOD) from ovaries with functional CL (on day 5 after PMSG). It increased P and E 2 and the activities of SOD and catalase (CAT) and decreased lipoperoxidation of ovaries with regressing CL (on day 9 after PMSG). Treatment with DHEA did not affect the production of prostaglandin F 2a (PGF 2a ) or PGE by ovaries with functional CL, whereas DHEA decreased PGF 2a and increased PGE production by ovaries with regressing CL. Metformin (50 mg/kg body weight, orally) given together with DHEA restored E 2 levels from mice with ovaries with functional CL and serum P, PGF 2a and PGE levels, and oxidative balance in mice with ovaries with regressing CL. Metformin alone was able to modulate serum P and E 2 levels, lipoperoxidation, SOD and CAT, and the 5,5-dimethyl-1-pyrroline N-oxide/ % OH signal. These findings suggest that hyperandrogenism is able to induce or to rescue CL from luteolysis and metformin treatment is able to prevent these effects.

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Section: Introductionmentioning

confidence: 66%

Section: Experimental Designmentioning

confidence: 99%

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Effect of DHEA and metformin on corpus luteum in mice

Sander¹,

Facorro²,

Piehl³

et al. 2009

Reproduction

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“…These investigations were initiated after a 43-year-old patient with severe DOR developed a typical polycystic ovary (PCO) phenotype over consecutive in vitro fertilization (IVF) cycles after self-medicating with DHEA [3]. DHEA has been utilized to induce PCO-like ovarian phenotypes in rats [4], and mice [5]. From subsequent observational studies we then concluded that DHEA significantly and beneficially affects functional ovarian reserve (FOR), egg and embryo quality and overall pregnancy chances in women with DOR [6].…”

Section: Introductionmentioning

confidence: 99%

Starting and resulting testosterone levels after androgen supplementation determine at all ages in vitro fertilization (IVF) pregnancy rates in women with diminished ovarian reserve (DOR)

Gleicher

Kim

Weghofer

et al. 2012

J Assist Reprod Genet

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Purpose To investigate whether androgen conversion rates after supplementation with dehydroepiandrosterone (DHEA) differ, and whether differences between patients with diminished ovarian reserve (DOR) are predictive of pregnancy chances in association with in vitro fertilization (IVF).Methods In a prospective cohort study we investigated 213 women with DOR, stratified for age (≤38 or >38 years) and ovarian FMR1 genotypes/sub-genotypes. All women were for at least 6 weeks supplemented with 75 mg of DHEA daily prior to IVF, between initial presentation and start of 1st IVF cycles. Levels of DHEA, DHEA-sulfate (DHEAS), total T (TT) and free T (FT) at baseline ( BL ) and IVF cycle start ( CS ) were then compared between conception and non-conception cycles. Results Mean age for the study population was 41.5 ± 4.4 years. Forty-seven IVF cycles (22.1 %) resulted in clinical pregnancy. Benefits of DHEA on pregnancy rates were statistically associated with efficiency of androgen conversion from DHEA to T and amplitude of T gain. Younger women converted significantly more efficiently than older females, and selected FMR1 genotypes/sub-genotypes converted better than others. FSH/androgen and AMH/androgen ratios represent promising new predictors of IVF pregnancy chances in women with DOR. Conclusions DOR at all ages appears to represent an androgen-deficient state, benefitting from androgen supplementation. Efficacy of androgen supplementation with DHEA, however, varies depending on female age and FMR1 genotype/sub-genotype. Further clarification of FMR1 effects should lead to better individualization of androgen supplementation, whether via DHEA or other androgenic compounds.

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“…Therefore, the treatment with DHEA led to a selective ovarian CD4 þ and CD8 þ T lymphocyte expression characterized by both a diminution of the percentage of CD4 þ lymphocytes and an increase in the percentage of CD8 þ T lymphocytes (Luchetti et al 2004). In view of our previous studies and those reported by Lu et al (2002), who demonstrated that production of cytokines by B cells is controlled by an enriched CD8 þ T lymphocyte population and steroid hormones, experiments were designed to evaluate whether DHEA was able to lead to a selective T lymphocyte population that could, in turn, regulate cytokine production.…”

Section: Introductionmentioning

confidence: 99%

Role of the N, N′-dimethylbiguanide metformin in the treatment of female prepuberal BALB/c mice hyperandrogenized with dehydroepiandrosterone

Sander¹,

Luchetti²,

Solano³

et al. 2006

Reproduction

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The present study investigated the role of the N, N{ 0 }-dimethylbiguanide metformin (50 mg/100 g body weight in 0.05 ml water, given orally with a canulla) in the prevention of endocrine and immune disorders provoked by the hyperandrogenization with dehydroepiandrosterone (DHEA) in prepuberal BALB/c mice. The treatment with DHEA (6 mg/100 g body weight in 0.1 ml oil) for 20 consecutive days, recreates a mouse model that resembles some aspects of the human polycystic ovary syndrome (PCOS). The treatment with DHEA did not modify either body mass index (BMI) or blood glucose levels, but did increase fasting insulin levels when compared with controls. Markers of ovarian function -serum estradiol (E), progesterone (P) and ovarian prostaglandin E (PGE) -were evaluated. The treatment with DHEA increased serum E and P levels while ovarian PGE diminished. When metformin was administered together with DHEA, serum insulin, E and P levels, and ovarian PGE values did not differ when compared with controls. Using flow cytometry assays we found that the treatment with DHEA diminished the percentage of the CD4 1 T lymphocyte population and increased the percentage of the CD8 1 T lymphocyte population from both ovarian tissue and retroperitoneal lymph nodes. However, when metformin was administered together with DHEA, the percentages of CD4 1 and CD8 1 T lymphocyte populations from both ovarian tissue and retroperitoneal lymph nodes were similar to those observed in controls. Finally, when DHEA was administered alone it increased the serum tumor necrosis factor-alpha (TNF-a) levels when compared with controls; however, when metformin was administered together with DHEA, serum TNF-a levels were similar to controls. These results indicate that metformin is able, directly or indirectly, to avoid the endocrine and immune alterations produced when mice are hyperandrogenized with DHEA.

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Effects of dehydroepiandrosterone on ovarian cystogenesis and immune function

Cited by 92 publications

References 45 publications

Effect of DHEA and metformin on corpus luteum in mice

Effect of DHEA and metformin on corpus luteum in mice

Starting and resulting testosterone levels after androgen supplementation determine at all ages in vitro fertilization (IVF) pregnancy rates in women with diminished ovarian reserve (DOR)

Role of the N, N′-dimethylbiguanide metformin in the treatment of female prepuberal BALB/c mice hyperandrogenized with dehydroepiandrosterone

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