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The effects of metformin and letrozole on endometrium and ovary in a rat model


Oner, Gokalp (contact); Ozcelik, Bulent; Ozgun, Mahmut; Ozturk, Figen

Abstract: Objective: The effects of metformin and letrozole on endometrium and ovarian reserve were studied in a rat model.

Methods: Forty female Wistar albino mature rats at 8 weeks, weighing 180–260 g, were used for the study. These rats were randomly divided into four groups. Control group, 8 rats, was given no medication by oral gavage. The rats in low-dose metformin group, 10 rats, were given 100 mg/kg/day of oral metformin. The rats in high-dose metformin group, 10 rats, were given 200 mg/kg/day of oral metformin. The rats in letrozole, 10 rats, were given 0.1 mg/kg/day of oral letrozole.

Results: There was statistically significant difference in the endometrial thickness between the treatment groups and control group. The primordial follicle count was comparable in all treatment groups compared with control. Finally there was no significantly difference in total follicle count between the treatment groups and control.

Conclusions: This study showed that both metformin and letrozole had similar effects on endometrium and ovary in the rat model. Additionally metformin had a little effect on endometrium than letrozole. Although metformin and letrozole might have tendency to enhance the total follicle count in the rat model, they had comparable effects on ovarian follicles and did not change the ovarian reserve compared with control.

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Allopregnanolone, a GABAA receptor agonist, decreases gonadotropin levels in women. A preliminary study.

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Bixo, Marie (contact); Timby, Erika; Hedström, Helena; Bäckström, Torbjörn; Sundstrom-Poromaa, Inger; Nyberg, Sigrid

Abstract: Animal studies suggest regulatory effects on the hypothalamic-pituitary-gonad axis by allopregnanolone, an endogenous GABAA receptor agonist. Elevated levels of allopregnanolone in women with hypothalamic amenorrhea have been seen. Isoallopregnanolone is an isomer to allopregnanolone, but without GABAA receptor effects. The purpose of this study was to investigate effects of allopregnanolone and isoallopregnanolone on gonadotropin levels in healthy women of fertile age. Ten women were given allopregnanolone and five women isoallopregnanolone intravenously in follicular phase. Repeated blood samples were drawn during the test day. Main outcomes were changes in serum levels of FSH, LH, oestradiol and progesterone.

Serum-FSH decreased between 5 and 105 minutes after the allopregnanolone injection (F(16,144) = 2.18, p = 0.008). Serum-LH were reduced between 5 and 35 minutes following the allopregnanolone injection (F(16,144) = 2.63, p = 0.001). Serum-oestradiol and -progesterone were not significantly changed after allopregnanolone injections. No effect on gonadotropin levels were seen after administration of isoallopregnanolone. Allopregnanolone reduces FSH and LH levels in women and the effect might be mediated via a specific GABAA receptor activation since isoallopregnanolone lacked this effect. Although the number of women was small, the results suggest a regulatory mechanism on the hypothalamic-pituitary-gonadal axis by allopregnanolone.

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Transcription of Estrogen Receptor α (ERα) and Mitochondrial Cytochrome b (MTCYB) Genes in Uterine Leiomyomas

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Shaik, Noor (contact); Lone, Waseem; Khan, Imran; Kaipa, Prabhakar; Kodati, Vijaya; Hasan, Qurratulain Enhanced

Abstract: The relative expression levels of ERα and MTCYB transcripts and their association with ERα,-397T>C gene polymorphism was determined in premenopausal uterine leiomyomas and myometrium tissues to gain an insight into the role of ER mediated action of estrogen on mitochondrial gene transcription. Both ERα and MTCYB transcripts were over expressed in leiomyomas compared to myometrium tissues with 9.18±0.79 folds and 5.24±0.48 folds respectively. ERα demonstrated ≥ 1.7 folds over expression expressed over MTCYB (P<0.001). Genotype correlation with transcript expression revealed that leiomyomas with CC genotype had significantly increased levels of ERα with 11.9±1.02 folds as compared to 6.46 ±0.56 folds seen in CT and TT genotypes together (p < 0.001). Interestingly, MTCYB transcript levels were also >1.9 folds over expressed in leiomyomas with the CC genotype as compared to leiomyomas with other genotypes (p<0.01).Significant elevation of ERα and MTCYB transcript levels in premenopausal leiomyomas and its association with ERα,-397 CC genotype suggests the mitochondrial mediated role of estrogen as the promoter of leiomyoma tumorigenesis.

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Bianco, Bianca (contact); Christofolini, Denise; Teles, Juliana; Vilarino, Fábia; André, Gustavo; Barbosa, Caio

Abstract: Estrogens are important factors in the development of endometriosis, and can induce cell proliferation and stimulate cell division. COMT constitutes a crucial element in estrogen metabolism and has been suggested to be involved in the development of endometriosis. This study had the objective of to determine if the presence of COMT val/met polymorphism (rs4680) increases the risk to endometriosis in infertile patients. A case-control study that included 198 infertile women with endometriosis, 71 infertile women without endometriosis and 168 fertile women as control group of the Faculdade de Medicina do ABC. COMT (val/met) genotypes were identified by real time PCR (genotyping TaqMan assay) and the results were analyzed statistically by chi-squared test. The data showed no statistical difference in the distribution of COMT genotypes neither between infertile patients with endometriosis and control group (p=0.567), regardless disease degree, nor between infertile patients without endometriosis and control group (p=0.460). In conclusion, the COMT val/met polymorphism is not associated to endometriosis-related infertility in the Brazilian population evaluated. However, more studies in larger populations are necessary to confirm these results.

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Hydrogen Sulfide Inhibits the Spontaneous and Oxytocin-Induced Contractility of Human Pregnant Myometrium


Ni, Xin; Hu, Rong; Lu, Jianqiang; You, Xingji; Zhu, Xiaoyan; Hui, Ning

Hydrogen sulfide (H2S) is a novel endogenous gaseous signaling transmitter in mammalian tissues including smooth muscle tissues. We investigated the effect of NaHS, a H2S donor, on the contractility of isolated human myometrium strips from term pregnant women who were undergoing labour. Cumulative effects of NaHS on spontaneous and oxytocin-induced contractility were evaluated by using isometric tension recordings. NaHS (0.1υM-1mM) concentration-dependently inhibited spontaneous contractility of labouring myometrium, with a decrease in amplitude and frequency. NaHS (0.1υM-1mM) decreased the frequency but not the amplitude of oxytocin (1υM)-induced contractions. NaHS-induced relaxation could be prevented by pretreatment with glibenclamide, an inhibitor of K+ATP channels. Thus, NaHS evokes relaxation of human pregnant myometrium, suggesting a possible role of H2S during human pregnancy.

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