Anti-Müllerian hormone is a specific marker of Sertoli- and granulosa-cell origin in gonadal tumors

Rey, Rodolfo

doi:10.1053/hupa.2000.18498

Cited by 173 publications

(105 citation statements)

References 35 publications

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“…In contrast to AFC and inhibin B (7, 11), AMH may not only reflect the number of early and developing antral follicles, but also earlier stages of follicle development, as was shown both in animal and human studies (12,13,28,29). However, the contribution of the different follicle stages to the final serum AMH level is unknown.…”

Section: Discussionmentioning

confidence: 99%

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Serum antimüllerian hormone levels best reflect the reproductive decline with age in normal women with proven fertility: A longitudinal study

Rooij

Broekmans

Scheffer

et al. 2005

Fertility and Sterility

518

287

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Objective: The aim of this study was to assess which of the basal ovarian reserve markers provides the best reflection of the changes occurring in ovarian function over time (i.e., reproductive aging). Design: Prospective longitudinal study. Setting: Healthy volunteers in an academic research center. Patient(s): Eighty-one women with normal reproductive performance during the course of their lives were longitudinally assessed. In this select group of women, becoming chronologically older was considered as a proxy variable for becoming older from a reproductive point of view. Intervention(s):The women were assessed twice, with on average a 4-year interval (T 1 and T 2 ). The number of antral follicles on ultrasound (AFC) and blood levels of antimüllerian hormone (AMH), FSH, inhibin B, and E 2 were assessed. Main Outcome Measure(s): Longitudinal changes of the markers mentioned and the consistency of these parameters over time. Result(s):The mean ages at T 1 and T 2 were 39.6 and 43.6 years, respectively. Although AFC was strongly associated with age in a cross-sectional fashion, it did not change over time. The AMH, FSH, and inhibin B levels showed a significant change over time, in contrast to E 2 levels. The AMH and AFC were highly correlated with age both at T 1 and T 2 , whereas FSH and inhibin B predominantly changed in women more than 40 years of age. To assess the consistency of these parameters over time, we investigated whether a woman's individual level above or below the mean of her age group at T 1 remained above or below the mean of her age group at T 2 . Serum AMH concentrations showed the best consistency, with AFC as second best. The FSH and inhibin B showed only modest consistency, whereas E 2 showed no consistency at all. Conclusion(s):These results indicate that serum AMH represents the best endocrine marker to assess the age-related decline of reproductive capacity. (Fertil Steril 2005;83:979 -87.

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Section: Discussionmentioning

confidence: 99%

“…Recently, serum antimüllerian hormone (AMH) levels have been introduced as a novel measure of ovarian reserve. AMH is a product of granulosa cells of the preantral and antral follicles (12,13). Serum AMH levels decline with age and are related to the number of antral follicles and to the ovarian response after ovarian hyperstimulation (14 -18).…”

mentioning

confidence: 99%

Serum antimüllerian hormone levels best reflect the reproductive decline with age in normal women with proven fertility: A longitudinal study

Rooij

Broekmans

Scheffer

et al. 2005

Fertility and Sterility

518

287

View full text Add to dashboard Cite

show abstract

“…AMH is mainly secreted by the granulosa cells of the pre-antral and antral follicles [93,94] and its declining levels with age might be related to the diminishing number of antral follicles and reduced ovarian reserve [92,[95][96][97].…”

Section: Menopausementioning

confidence: 99%

Reproductive ageing in women

Djahanbakhch

Ezzati

Zosmer

2007

The Journal of Pathology

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The traditional view in respect to female reproduction is that the number of oocytes at birth is fixed and continuously declines towards the point when no more oocytes are available after menopause. In this review we briefly discuss the embryonic development of female germ cells and ovarian follicles. The ontogeny of the hypothalamic-pituitary-gonadal axis is then discussed, with a focus on pubertal transition and normal ovulatory menstrual cycles during female adult life. Biochemical markers of menopausal transition are briefly examined. We also examine the effects of age on female fertility, the contribution of chromosomal abnormalities of the oocyte to the observed decline in female fertility with age and the possible biological basis for the occurrence of such abnormalities. Finally, we consider the effects of maternal age on obstetric complications and perinatal outcome. New data that have the potential to revolutionize our understanding of mammalian oogenesis and follicular formation, and of the female reproductive ageing process, are also briefly considered.

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“…19 AMH has been indicated as a growth inhibitor of AMHRII-positive ovarian cancer cells in vitro [20][21][22][23] and in vivo, [24][25][26][27] and this growth-inhibitory effect is characterized by a block in the cell cycle progression and subsequent apoptosis. 20,22 Although AMH has been indicated as a tissue marker for GCTs, 28 AMH immunoreactivity in a series of 80 primary GCTs was low or negative in the tumors larger than 10 cm in diameter. 29 This suggests that the lack of AMH may give these tumors growth potential, but the role of AMH signaling in human GCTs remains unraveled.…”

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confidence: 99%

Anti-Müllerian hormone inhibits growth of AMH type II receptor-positive human ovarian granulosa cell tumor cells by activating apoptosis

Anttonen

Färkkilä

Tauriala

et al. 2011

Laboratory Investigation

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Ovarian granulosa cell tumors (GCTs) are sex cord stromal tumors that constitute 3-5% of all ovarian cancers. GCTs usually present with an indolent course but there is a high risk of recurrence, which associates with increased mortality, and targeted treatments would be desirable. Anti-Mü llerian hormone (AMH), a key factor regulating sexual differentiation of the reproductive organs, has been implicated as a growth inhibitor in ovarian cancer. GCTs and normal granulosa cells produce AMH, but its expression in large GCTs is usually downregulated. Further, as the lack of specific AMHsignaling pathway components leads to GCT development in mice, we hypothesized that AMH inhibits growth of GCTs. Utilizing a large panel of human GCT tissue samples, we found that AMH type I receptors (ALK2, ALK3 and ALK6) and type II receptor (AMHRII), as well as their downstream effectors Smad1/5, are expressed and active in GCTs. AMHRII expression was detected in the vast majority (96%) of GCTs and correlated with AMH mRNA and protein expression. AMH mRNA level was low in large GCTs, confirming previous findings on low-AMH protein expression in large human as well as mouse GCTs. To study the functional role of AMH in this peculiar ovarian cancer, we utilized a human GCT cell line (KGN) and 10 primary GCT cell cultures. We found that the AMH-Smad1/5-signaling pathway was active in these cells, and that exogenous AMH further activated Smad1/5 in KGN cells. Furthermore, AMH treatment reduced the number of KGN cells and primary GCT cells, with increasing amounts of AMH leading to augmented activation of caspase-3 and subsequent apoptosis. All in all, these data support the premise that AMH is a growth inhibitor of GCTs.

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Anti-Müllerian hormone is a specific marker of Sertoli- and granulosa-cell origin in gonadal tumors

Cited by 173 publications

References 35 publications

Serum antimüllerian hormone levels best reflect the reproductive decline with age in normal women with proven fertility: A longitudinal study

Serum antimüllerian hormone levels best reflect the reproductive decline with age in normal women with proven fertility: A longitudinal study

Reproductive ageing in women

Anti-Müllerian hormone inhibits growth of AMH type II receptor-positive human ovarian granulosa cell tumor cells by activating apoptosis

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