The role of activin, follistatin and inhibin in testicular physiology

Kretser, David M de; Buzzard, Jeremy J; Okuma, Yoshinori; O’Connor, Anne E; Hayashi, Tetsuo; Lin, Shyr-Yeu; Morrison, John R.; Loveland, Katherine A.; Hedger, Mark P.

doi:10.1016/j.mce.2004.07.008

Cited by 85 publications

(55 citation statements)

References 94 publications

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“…inhba was downregulated by both gonadotropins, whereas inhbb was moderately downregulated by Lh. In rodents, numerous in vivo and in vitro studies have demonstrated the importance of activin A and its regulators (inhibin and follistatin) in the control of spermatogenesis (de Kretser et al 2004, Barakat et al 2008. In fetal and postnatal testis, activin A promotes both Sertoli cell and gonocyte proliferation but hampers the differentiation of gonocytes in spermatogonia (Mithraprabhu et al 2010, Fan et al 2012.…”

Section: Discussionmentioning

confidence: 99%

Fsh and Lh have common and distinct effects on gene expression in rainbow trout testis

Sambroni¹,

Rolland²,

Lareyre³

et al. 2012

Journal of Molecular Endocrinology

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The general rules established from mammalian species for the regulation of spermatogenesis by gonadotropins may not be fully relevant in fish. Particularly, Fsh is as potent as Lh to stimulate steroidogenesis and the Fsh receptor is expressed in Leydig cells. In seasonal breeders, Fsh is likely the major gonadotropin involved in spermatogenesis onset and Lh is required to support spermatogenesis progression and gamete release. However, the genes that relay the action of Fsh and Lh have been poorly investigated in fish. The present study was aimed at identifying gonadotropin-dependent genes expressed in the testis during fish puberty. We cultured pubertal trout testicular explants for 96 h, with or without gonadotropin, and analyzed transcriptome variations using microarrays. Fsh and Lh had similar effects on a large group of genes while other genes were preferentially regulated by one or the other gonadotropin. We showed that most of the responsive genes were expressed in somatic cells and exhibited relevant patterns during the seasonal reproductive cycle. Some genes preferentially modulated by Lh could be involved in testicular cell fate (pvrl1 and bty) or sperm maturation (ehmt2 and racgap1) and will deserve further examination. Besides Fsh's effects on the steroidogenic pathway, our study demonstrates that Fsh coordinates relevant stimulatory and inhibitory paracrine factors known to regulate early germ cell proliferation and differentiation. Some of these genes belong to major regulatory pathways including the Igf pathway (igf1b/igf3 and igfbp6), the Tgfb pathway (amh, inha, inhba, and fstl3), the Wnt pathway (wisp1), and pleiotrophin (mdka).

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Section: Discussionmentioning

confidence: 99%

Fsh and Lh have common and distinct effects on gene expression in rainbow trout testis

Sambroni¹,

Rolland²,

Lareyre³

et al. 2012

Journal of Molecular Endocrinology

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“…The clinical value of the inhibin B assay is emphasized by the fact that in contrast to FSH, inhibin B is produced inside the testis and might reflect close interactions between Sertoli and germ cells (36,37). Thus, inhibin B levels correlate directly with spermatogenesis and reflect testicular sperm production.…”

Section: European Journal Of Endocrinologymentioning

confidence: 99%

The serum inhibin B concentration and reference ranges in normozoospermia

Barbotin

Ballot

Sigala

et al. 2015

European Journal of Endocrinology

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Objective: Although an inhibin B assay may be useful in the assessment of testicular function in a number of genital conditions, reliable reference ranges are still lacking. The present study sought to establish the reference range for serum inhibin B by applying the updated Gen II assay. Design: This prospective study included 818 men referred for semen analysis: 377 were normozoospermic (reference group) and 441 presented at least one abnormal semen parameter (case group). Methods: Semen parameters were interpreted according to the 2010 World Health Organization manual and David's modified classification for normal morphology. The inhibin B concentration was determined with the current ELISA. Results: In the reference group, the 2.5th percentile for inhibin B was 92 pg/ml and the 97.5th percentile for FSH was 7.8 IU/l. In the overall population, an inhibin B level !92 pg/ml was associated with increased odds ratio (OR; 95% CI) for oligozoospermia (16.93 (9.82-29.18), P!0.0001), asthenozoospermia (4.87 (2.88-8.10), P!0.0001), and teratozoospermia (2.20 (1.31-3.68), PZ0.0026). The combination of a FSH O7.8 IU/l and an inhibin B !92 pg/ml was associated with greater OR for oligozoospermia (98.74 (23.99-406.35), P!0.0001) than for each hormone considered separately. Conclusions: A new reference range for serum inhibin B was established by the use of updated immunoassay. The correlations between hormone levels and semen parameters highlighted the importance of establishing these values with respect to the spermogram. When combined with FSH assay, the inhibin B range may be of value in the evaluation of spermatogenesis in a number of male genital conditions.

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“…Preliminary results indicate that the follistatins increase the response of reporter cells to AMH N,C (Kawagishi et al 2014). Follistatins are classical inhibitors of the activins (de Kretser et al 2004, Hedger & de Kretser 2013, which activate the SMAD2/3 intracellular pathway (Shi & Massague 2003). Consequently, when follistatins are present, the balance between AMH-induced activation of SMAD1/5/8 and activin-induced activation of SMAD2/3 may be altered, although in vivo work is needed to prove this.…”

Section: And In the Calbindinmentioning

confidence: 99%

Anti-Müllerian hormone is a gonadal cytokine with two circulating forms and cryptic actions

McLennan¹,

Pankhurst²

2015

Journal of Endocrinology

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Anti-Mü llerian hormone (AMH) is a multi-faceted gonadal cytokine. It is present in all vertebrates with its original function in phylogeny being as a regulator of germ cells in both sexes, and as a prime inducer of the male phenotype. Its ancient functions appear to be broadly conserved in mammals, but with this being obscured by its overt role in triggering the regression of the Mü llerian ducts in male embryos. Sertoli and ovarian follicular cells primarily release AMH as a prohormone (proAMH), which forms a stable complex (AMH N,C ) after cleavage by subtilisin/kexin-type proprotein convertases or serine proteinases. Circulating AMH is a mixture of proAMH and AMH N,C , suggesting that proAMH is activated within the gonads and putatively by its endocrine target-cells. The gonadal expression of the cleavage enzymes is subject to complex regulation, and the preliminary data suggest that this influences the relative proportions of proAMH and AMH N,C in the circulation. AMH shares an intracellular pathway with the bone morphogenetic protein (BMP) and growth differentiation factor (GDF) ligands. AMH is male specific during the initial stage of development, and theoretically should produce male biases throughout the body by adding a male-specific amplification of BMP/GDF signalling. Consistent with this, some of the male biases in neuron number and the non-sexual behaviours of mice are dependent on AMH. After puberty, circulating levels of AMH are similar in men and women. Putatively, the function of AMH in adulthood maybe to add a gonadal influence to BMP/GDF-regulated homeostasis.

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The role of activin, follistatin and inhibin in testicular physiology

Cited by 85 publications

References 94 publications

Fsh and Lh have common and distinct effects on gene expression in rainbow trout testis

Fsh and Lh have common and distinct effects on gene expression in rainbow trout testis

The serum inhibin B concentration and reference ranges in normozoospermia

Anti-Müllerian hormone is a gonadal cytokine with two circulating forms and cryptic actions

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