Mutational analysis of the mature peptide region of inhibin genes in Indian women with ovarian failure

Dixit, Hridesh; Deendayal, M.; Singh, Lalji

doi:10.1093/humrep/deh342

Cited by 80 publications

(60 citation statements)

References 28 publications

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“…The specific assays for both the isoforms of inhibin also suggested a differential role that inhibin B may be a useful marker for follicular development and that inhibin A may indicate functionality of CL. Recently single nucleotide polymorphisms (SNPs) of inhibin A gene and its association of premature ovarian failure have gained a lot of attention in clinical research related to reproductive disorders [81][82][83]. Activin A and inhibin A measurement throughout pregnancy may have clinical usefulness in terms of diagnosing many gestational diseases (37) Both inhibin A and activin A serve as markers for assessment of perimenopausal changes, trophoblast viability, tumours and diagnosis of hypertensive disturbances of gestation [84].…”

Section: Inhibins In Clinical Reproductive Medicinementioning

confidence: 99%

New targets for old hormones: inhibins clinical role revisited [Review]

2011

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Abstract. Inhibins are gonadal peptide hormones belonging to the transforming growth factor-β (TGF-β) superfamily that regulate the pituitary follicle stimulating hormone (FSH) secretion by negative feedback mechanisms. It is evident that the understanding of inhibins function in the hypothalamic-pituitary-gonadal axis will provide insights into physiology and pathology of the gonadal function. In recent years, a great deal of attention has been focussed on clinical relevance of measuring circulating inhibins in normal and disease state. The past few years also have witnessed the emergence and discovery of extra pituitary action of inhibins that might provide further insights into the underlying diseases like cancer especially in the reproductive axis and various other new endocrine target organs. In this review after systematic analysis of literature, we discuss briefly the known and recent advances in function of these hormones highlighting also its structure, production and mechanisms of signal transduction. Also this review discusses about the physiological relevance of inhibin association in the normal function to the development of reproductive cancers. Finally, we describe evidence from various emerging studies that inhibins make an important contribution to other physiological functions apart from reproduction which reveals new endocrine target organs of inhibins. The emerging view is inhibin participates in multiple ways to regulate the function in different cell types and still complete repertoire of its actions is under investigation. Key words: Inhibin, Transforming growth factor, Ovarian cancer, Activins, BetaglycanMAMMAliAn reproduction is intricate, highly ordered and is coordinated by assorted neural, neuroendocrine, endocrine, autocrine and paracrine cell-cell communication pathways. Many of the pioneering discoveries meticulously demonstrated the roles of hypothalamic gonadotropin releasing hormone (GnRH) that stimulates pituitary gonadotropins such as follicle stimulating hormone (FSH) and leutinizing hormone (LH), which directly control gonadal functions. Subsequent breakthroughs in the advancement of molecular biology and in understanding signal transduction mechanisms suggested involvement of various cytokines and growth factors at each level of the hypothalamic-pituitary-gonadal axis in the paracrine/autocrine control of different programmed reproductive events. Members include inhibins and activins, belonging to the transforming growth factor (TGF-β) super family and follistatin (FS), a structurally distinct though functionally related molecule. It has been more than 70 years since the identification of negative feedback control of pituitary FSH secretion by inhibins. These factors also were shown to act in autocrine, endocrine or paracrine manner within the reproductive tissues, but the identification of specific pathways in different cellular context along the gonadal axis is still quite unclear and should thus be further investigated. The discovery process of extra pituitary action of ...

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Section: Inhibins In Clinical Reproductive Medicinementioning

confidence: 99%

New targets for old hormones: inhibins clinical role revisited [Review]

2011

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“…An inhibin ␣-subunit variant (A257T; Fig. 1B) within the N-terminal region of the mature protein was identified as a non-conserved amino acid sequence change that is significantly associated with an increased incidence of premature ovarian failure (POF) (25)(26)(27)(28). POF is typically characterized by hypergonadotropism with circulating levels of follicle-stimulating hormone (FSH) in the postmenopausal range, and in some patients, at levels greater than 30 mIU/ml (29).…”

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confidence: 99%

Inhibin α-Subunit N Terminus Interacts with Activin Type IB Receptor to Disrupt Activin Signaling

Zhu

Lin

Zou

et al. 2012

Journal of Biological Chemistry

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Background:The inhibin ␤-subunit interacts with activin type II receptor to antagonize activin signaling. Results: The inhibin ␣-subunit N terminus binds ALK4 to antagonize activin signaling. Conclusion: Inhibin ␣-subunit binding to ALK4 supports potent antagonism of constitutive activin-stimulated FSH production in pituitary cells. Significance: Understanding the mechanisms underlying control of pituitary FSH synthesis may provide treatment approaches to reproductive endocrine disorders.

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“…Among them, there are GDF9, which is expressed in the oocyte and forms BMP15/GDF9 heterodimers [79], and inhibin A (INHA), that acts as a negative modulator of pituitary FSH synthesis or as a paracrine factor [80]. Rare insertion/deletion and missense variations in GDF9 [81][82][83][84] and INHA [85][86][87][88][89] have been observed in POF patients.…”

Section: Autosomal Candidate Genes Of Pofmentioning

confidence: 99%

Insight into the Genomics of Premature Ovarian Failure

Stigliani¹

2013

J Mol Genet Med

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Primary Ovarian Failure (POF) is an ovarian defect characterized by the premature depletion of ovarian follicles. It causes infertility in ~1% of women <40 years of age and it has important health consequences for affected patients. POF is a heterogeneous disease, which can develop as a result of a broad variety of pathogenic mechanisms including genetic, autoimmune and iatrogenic causes. However, the mechanisms that cause ovarian dysfunction are poorly understood. Focus on genetic component of the disease has revealed the existence of several causal genetic defects, thus indicating that in addition to some monogenic forms, POF may frequently be a multifactorial disease involving several gene abnormalities and chromosome aberrations. Moreover, most recent studies have highlighted that epigenetic mechanisms may give an additional contribution to POF pathogenesis. This review gives a picture of the state of the art of the complex genetic and epigenetic defects associated with POF, being it clear that a deep comprehension of the molecular etiology of POF may in future early identify those women with higher risk of POF.

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Mutational analysis of the mature peptide region of inhibin genes in Indian women with ovarian failure

Abstract: The INHalpha gene is a strong candidate gene for ovarian failure. Mutations in INHbetaB and INHbetaA genes are not associated with ovarian failure.

Cited by 80 publications

References 28 publications

New targets for old hormones: inhibins clinical role revisited [Review]

New targets for old hormones: inhibins clinical role revisited [Review]

Inhibin α-Subunit N Terminus Interacts with Activin Type IB Receptor to Disrupt Activin Signaling

Insight into the Genomics of Premature Ovarian Failure

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