The transforming growth factor beta (TGF-beta) family of growth factors control the development and homeostasis of most tissues in metazoan organisms. Work over the past few years has led to the elucidation of a TGF-beta signal transduction network. This network involves receptor serine/threonine kinases at the cell surface and their substrates, the SMAD proteins, which move into the nucleus, where they activate target gene transcription in association with DNA-binding partners. Distinct repertoires of receptors, SMAD proteins, and DNA-binding partners seemingly underlie, in a cell-specific manner, the multifunctional nature of TGF-beta and related factors. Mutations in these pathways are the cause of various forms of human cancer and developmental disorders.

TGF-beta signal transduction.

https://www.fertstert.org/article/S0015-0282(01)02993-4/pdf

Antimüllerian hormone serum levels: a putative marker for ovarian aging.

BACKGROUND The measurement of circulating anti-Mullerian hormone (AMH) has been applied to a wide array of clinical applications, mainly based on its ability to reflect the number of antral and pre-antral follicles present in the ovaries. AMH has been suggested to predict the ovarian response to hyperstimulation of the ovaries for IVF and the timing of menopause, and to indicate iatrogenic damage to the ovarian follicle reserve. It has also been proposed as a surrogate for antral follicle count (AFC) in the diagnosis of polycystic ovary syndrome (PCOS). METHODS This paper is a summary of presentations at a European Society of Human Reproduction and Embryology campus workshop on AMH, with literature cited until September 2013. Published peer-reviewed medical literature about AMH was searched through MEDLINE and was subjected to systematic review and critical assessment by the panel of authors. RESULTS Physiologically, recent data confirm that AMH is a follicular gatekeeper limiting follicle growth initiation, and subsequently estradiol production from small antral follicles prior to selection. AMH assays continue to evolve and technical issues remain; the absence of an international standard is a key issue. The dynamics of circulating AMH levels throughout life can be split into several distinct phases, with a peak in the early 20s before a decline to the menopause, with a strong and positive correlation with non-growing follicle recruitment. There is a more complex rise during childhood and adolescence, which is likely to be more reflective of different stages of follicle development. AMH shows limited short-term variability, but the influence of states such as prolonged oral contraceptive use need to be considered in clinical assessment. There are only very limited data on relationships between AMH and natural fertility at different stages of reproductive life, and while it has a relationship to age at menopause the marked variability in this needs further exploration. AMH may be useful in assessing the need for fertility preservation strategies and detecting post-chemotherapy or surgical damage to the ovarian reserve. Long-term follow-up of patients to ascertain fully the value of post-cancer serum AMH in predicting long-term ovarian function is required. There is a linear relationship between AMH and oocyte yield after ovarian stimulation, which is of value in predicting ovarian hyperstimulation. AMH can also identify 'poor responders', but it seems inappropriate at present to withhold IVF purely on this basis. Women with PCOS show markedly raised AMH levels, due to both the increased number of small antral follicles and intrinsic characteristics of those granulosa cells, and this may contribute to anovulation. The value of AMH in the diagnosis of PCOS remains controversial, but it may replace AFC in the future. CONCLUSIONS For the first time in female reproductive biology, it is possible to measure the submerged part of the iceberg of follicle growth, i.e. the intrinsic, so-called 'acyclic' ovarian activity. An international standard for AMH and improved assay validity are urgently needed to maximize the clinical utility of this very promising biomarker of ovarian function in a large array of clinical situations, both in childhood and adulthood.

The physiology and clinical utility of anti-Müllerian hormone in women

Anti-Mullerian hormone (AMH) is a member of the transforming growth factor beta family of growth and differentiation factors. In the ovary, AMH has an inhibitory effect on primordial follicle recruitment as well as on the responsiveness of growing follicles to follicle-stimulating hormone (FSH). The ovary-specific expression pattern in granulosa cells of growing nonselected follicles makes AMH an ideal marker for the size of the ovarian follicle pool. This review summarizes recent findings concerning AMH and its role as a marker for the quantitative aspect of ovarian reserve as well as ovarian dysfunction.

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Anti-Müllerian hormone: a new marker for ovarian function

TGF-β Superfamily Signaling in Embryonic Development and Homeostasis

Publisher Summary
This chapter describes anti-Mullerian hormone. It discusses the molecular mechanisms of gene expression and protein bioactivity and the clinical applications of AMH research. In Jost's laboratory, the factor responsible for Mullerian regression was called hormone inhibitrice. The homozygosity of the mutated allele was established by the results of allele-specific hybridization, which showed that the patient's DNA hybridized only with the mutant oligonucleotide probe and not with the wild-type one. Identical results were obtained with DNA from the two other affected siblings. Although involved in male sex differentiation, the AMH gene is not located on a sex chromosome, in keeping with the tenet that only the genetic trigger for gonadal sex determination needs to be sex specific. Recent data on the location of the AMH gene in other species are available at present. No association to genes located on human chromosome 19 has been detected, indicating complex rearrangements in chromosomal structure during evolution.

Anti-müllerian hormone: the Jost factor.

Anti-Mullerian hormone (AMH), also called MUllerian inhibiting substance (MIS) is a product of supporting gonadal Sertoli and granulosa cells Its main physiological role is the induction of regression of Mullerian ducts in male fetuses but it also plays a role in Leydig cell steroidogenesis and in follicular development It is a member of the transforming growth factor B family and signals through two serine/threonine kinase receptors, only one of whom, type II, is specific Type I receptors and the intracytoplasmic signaling molecules are shared with the bone morphogenetic family AMH is positively regulated by SF1, SOX9 and FSH Testosterone is a powerful downregulator Males lacking functional AMH or AMH receptor genes do not undergo regression of MUllerian derivatives during fetal life AMH is an excellent marker of prepubertal testicular function and has gained recognition as a valuable marker of follicular reserve in adult women

di Clemente N

Papers

Anti-müllerian hormone: the Jost factor.

Testicular anti-Müllerian hormone: history, genetics, regulation and clinical applications.