Estrogens and androgens affect human luteal cell function

Tropea, Anna; Lanzone, Antonio; Tiberi, Federica; Romani, Federica; Catino, Stefania; Apa, Rosanna

doi:10.1016/j.fertnstert.2010.02.009

Cited by 12 publications

(9 citation statements)

References 33 publications

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“…A recent study has shown that IGF1 and IGF-binding proteins form the main system of induction of estrogen synthesis in luteinized granulosa cells and act synergistically with FSH and LH in controlling granulosa aromatase levels [19]. Aromatase mRNA expression was significantly lower after a 30-min incubation with insulin than in the M30 group, in agreement with previous studies [22,23]. …”

Section: Discussionsupporting

confidence: 88%

“…Tropea et al [23] found that estrogens and androgens might affect human luteal cell function by modulating aromatase activity and other luteolytic cytokines. In a study by Mansfield et al [22], metformin consistently inhibited insulin-stimulated estradiol and progesterone production in granulosa cells and had about equal and opposite effects on progesterone and androstenedione production by theca cells.…”

Section: Discussionmentioning

confidence: 99%

“…The inhibition of mRNA aromatase expression by metformin in our study, together with the results reported by Mansfield et al [22], indicates that metformin may act at multiple points of the steroid hormone synthesis pathway. Extrapolating our in vitro results, a possible role of metformin in reducing the insulin action in aromatase mRNA expression may lead to lower estradiol levels in the corpus luteum and have beneficial effects on progesterone release [23]. …”

Section: Discussionmentioning

confidence: 99%

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Human Granulosa Cells: Insulin and Insulin-Like Growth Factor-1 Receptors and Aromatase Expression Modulation by Metformin

Fuhrmeister

Branchini²,

Pimentel³

et al. 2014

Gynecol Obstet Invest

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Background/Aim: Granulosa cells are the source of the most important ovarian steroids. Even in patients without significant improvement in metabolic parameters, metformin has apparently an important effect on the ovary. The aim of this study was to evaluate gene and protein expression of an insulin receptor (IR), insulin-like growth factor-1 (IGF1) receptor (IGF1R) and aromatase in granulosa cells treated with metformin and insulin. Methods: Luteinized granulosa cells were collected from 27 patients during in vitro fertilization procedures. Cells were isolated, stored in culture for 24 h and divided into four groups: control; metformin for 30 min, and metformin for 30 min plus insulin for 30 or 60 min. Results: IR and IGF1R mRNA expression was significantly enhanced by metformin but was not affected by insulin. Aromatase mRNA expression was significantly reduced in metformin-incubated cells following stimulation with insulin for 30 min. No statistical differences were found in IGF1R and aromatase protein expression, and IR expression was not detected. Conclusion: A direct effect of metformin on the gene expression of IGF1R, IR and aromatase was observed. Further studies should investigate the role of IGF1R, IR and aromatase in ovarian physiology for a better understanding of the effect of metformin.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Human Granulosa Cells: Insulin and Insulin-Like Growth Factor-1 Receptors and Aromatase Expression Modulation by Metformin

Fuhrmeister

Branchini²,

Pimentel³

et al. 2014

Gynecol Obstet Invest

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“…76 It is plausible that hyperinsulinemia and hyperandrogenism, which are commonly seen in PCOS, contribute to VEGF upregulation in these women since insulin, LH, and androgens have all been shown to stimulate VEGF secretion by granulosa cells. 76,78,79 In support of this notion, insulin-mediated VEGF production in luteinized granulosa cells has been shown to be more sensitive to insulin in women with PCOS compared with women with no PCOS. 78 Moreover, women with hyperinsulinemic PCOS were demonstrated to have greater stromal Doppler blood flow and androstenedione levels and decreased sex-hormone binding globulin levels compared with normoinsulinemic PCOS and control women.…”

Section: Vascular Endothelial Growth Factor Familymentioning

confidence: 89%

The Emerging Role of Angiogenic Factor Dysregulation in the Pathogenesis of Polycystic Ovarian Syndrome

2015

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Polycystic ovarian syndrome (PCOS) is a common endocrine disorder in reproductive age affecting 5 to 7% of women. It is characterized by anovulatory infertility, hyperandrogenism, and polycystic ovaries. Angiogenesis in the ovary is critical for follicular growth, ovulation, and the subsequent development and regression of the corpus luteum. Accumulating evidence suggests that multiple angiogenic factors are dysregulated in PCOS, including vascular endothelial growth factor, angiopoietins, platelet-derived growth factor, transforming growth factor-β, and basic fibroblast growth factor. This angiogenic factor imbalance likely underlies the increased stromal vascularity observed in PCOS. Angiogenic factor dysregulation may play an important role in the pathophysiology of PCOS and may contribute to ovulatory dysfunction, subfertility, and ovarian hyperstimulation syndrome, which are commonly seen in women with PCOS. Further experimental studies are needed to gain a better understanding of the growth factors that are involved in normal and pathological ovarian angiogenesis, and to assess the potential of angiogenesis-based treatment strategies in PCOS.

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“…Estrogens and androgens inhibit progesterone secretion by the human corpus luteum. The effects of testosterone and androstenedione are mediated by their conversion to estrogens (Tropea et al, 2010). Androgens stimulate cytochrome P450 aromatase mRNA concentrations in granulosa cells.…”

Section: Ovarian Signalsmentioning

confidence: 99%