Inhibin at 90: From Discovery to Clinical Application, a Historical Review

Makanji, Yogeshwar; Zhu, Jie; Mishra, Rama K.; Holmquist, Chris; Wong, Way W.; Schwartz, Neena B.; Mayo, Kelly E.; Woodruff, Teresa K.

doi:10.1210/er.2014-1003

Cited by 147 publications

(149 citation statements)

References 495 publications

Supporting

Mentioning

137

Contrasting

Unclassified

Order By: Relevance

“…An alternative explanation might be slowing of the GnRH pulse generator which favors FSH secretion over LH [33]. Theoretically, FSH might be increased through defective negative feedback by inhibin B or increased action of activin A at the gonadotroph [34], but previous investigations reported no evidence for this hypothesis [35]. It should be noted that the observed increases in prolactin and FSH are still within the reference range and might therefore be considered helpful in our understanding of the function of IGSF1 rather than representing a clinically significant sign.…”

Section: Discussionmentioning

confidence: 99%

Pituitary Hormone Secretion Profiles in IGSF1 Deficiency Syndrome

Joustra

Roelfsema²,

Endert³

et al. 2015

Neuroendocrinology

View full text Add to dashboard Cite

Background: Loss-of-function mutations in immunoglobulin superfamily member 1 (IGSF1) cause an X-linked syndrome of central hypothyroidism, macroorchidism, delayed pubertal testosterone rise, variable prolactin deficiency and variable partial GH deficiency in childhood. The clinical features and gene expression pattern suggest a pivotal role for IGSF1 in the pituitary, but detailed knowledge on pituitary hormone secretion in this syndrome is lacking. We therefore aimed to study the 24-hour pituitary hormone secretion in male patients with IGSF1 deficiency. Methods: We collected blood samples every 10 min for 24 h in eight adult male IGSF1-deficient patients and measured circulating TSH, prolactin and gonadotropins. Deconvolution, modified cosinor and approximate entropy analyses were applied to quantify secretion rates, diurnal rhythmicity and regularity of hormone release. Results were compared to healthy controls matched for age and body mass index. Results: Compared to healthy controls, IGSF1-deficient patients showed decreased pulsatile secretion of TSH with decreased disorderliness and reduced diurnal variation. Basal and pulsatile secretion of FSH was increased by over 200%, while LH secretion did not differ from healthy controls. We observed a bimodal distribution of prolactin secretion, i.e. severe deficiency in three and increased basal and total secretion in the other five patients. Conclusion: The altered TSH secretion pattern is consistent with the previously hypothesized defect in thyrotropin-releasing hormone signaling in IGSF1 deficiency. However, the phenotype is more extensive and includes increased FSH secretion without altered LH secretion as well as either undetectable or increased prolactin secretion.

show abstract

Section: Discussionmentioning

confidence: 99%

Pituitary Hormone Secretion Profiles in IGSF1 Deficiency Syndrome

Joustra

Roelfsema²,

Endert³

et al. 2015

Neuroendocrinology

View full text Add to dashboard Cite

show abstract

“…We call attention to a recent, extensive review of the inhibins, which includes their historical, biological, and clinical importance (Makanji et al 2014).…”

Section: Inhibins and Betaglycanmentioning

confidence: 99%

Activins and Inhibins: Roles in Development, Physiology, and Disease

Namwanje

Brown

2016

Cold Spring Harb Perspect Biol

194

175

View full text Add to dashboard Cite

Since their original discovery as regulators of follicle-stimulating hormone (FSH) secretion and erythropoiesis, the TGF-β family members activin and inhibin have been shown to participate in a variety of biological processes, from the earliest stages of embryonic development to highly specialized functions in terminally differentiated cells and tissues. Herein, we present the history, structures, signaling mechanisms, regulation, and biological processes in which activins and inhibins participate, including several recently discovered biological activities and functional antagonists. The potential therapeutic relevance of these advances is also discussed.

show abstract

“…These are glycoprotein hormones that down-regulate follicle-stimulating hormone (FSH) production by the anterior pituitary whereas their counterparts, the Activins, up-regulate FSH production. Structurally, Inhibins are composed by two subunits, an α- and a β-subunit, linked by a disulfide bridge, while Activins are homodimers of β-subunits (reviewed in [8,9]). The signaling pathway for members of TGFβ superfamily is shared among TGFβ, BMPs and Activins, in which the dimeric ligands bind type I and type II receptors with serine/threonine kinase activity, leading to the phosphorylation of cytoplasmic proteins known as receptor SMADs, which then heterodimerize with the common SMAD (co-SMAD) and translocate to the nucleus to regulate gene expression (reviewed in [8]).…”

Section: Introductionmentioning

confidence: 99%

“…Thus, Inhibins were considered as ligands unable to induce signal transduction and through this mechanism they may antagonize Activin functions. However, several data have suggested the possibility that Inhibins may act through an independent receptor, although, an Inhibin-specific binding molecule has not yet been identified (reviewed in [9]).…”

Section: Introductionmentioning

confidence: 99%

A Key Role for Inhibins in Dendritic Cell Maturation and Function

et al. 2016

View full text Add to dashboard Cite

Inhibins are members of the TGFβ superfamily, which regulate many cellular processes including differentiation, proliferation, survival and apoptosis. Although initially described as hormones regulating the hypothalamus-pituitary-gonadal axis, based on their ability to antagonize Activins, our group has recently reported that they play a role in thymocyte differentiation and survival, as well as in thymic stromal cell maturation and nTreg generation. Here, we used Inhibin knock out mice (Inhα-/-) to investigate the role of Inhibins in peripheral dendritic cell maturation and function. We first demonstrated that LPS treated Inhα+/+ bone marrow derived dendritic cells (BMDC) were capable to produce significant levels of Inhibin A. Interestingly, Inhα-/- BMDC showed reduced MHCII and CD86 upregulation and increased PD-L1 expression in response to LPS compared to Inhα+/+, which correlated with reduced ability to induce proliferation of allogeneic T cells. The “semi-mature” phenotype displayed by Inhα-/- mBMDC correlated with increased levels of IL-10 and slightly decreased IL-6 production after LPS stimulation. In addition, Inhα-/- mBMDC showed impaired migration towards CCL19 and CCL21, assessed by in vitro chemotaxis and in vivo competitive homing experiments, despite their normal CCR7 expression. Furthermore, in vivo LPS-induced DC maturation was also diminished in Inhα-/- mice, specially within the LC (CD207+ CD11b+ CD103-) subpopulation. Finally, analysis of delayed type hypersensitivity responses in Inhα-/- mice, showed reduced ear swelling as a result of reduced cellular infiltration in the skin, correlating with impaired homing of CD207+ DCs to the draining lymph nodes. In summary, our data demonstrate for the first time that Inhibins play a key role in peripheral DC maturation and function, regulating the balance between immunity and tolerance.

show abstract

Inhibin at 90: From Discovery to Clinical Application, a Historical Review

Cited by 147 publications

References 495 publications

Pituitary Hormone Secretion Profiles in IGSF1 Deficiency Syndrome

Pituitary Hormone Secretion Profiles in IGSF1 Deficiency Syndrome

Activins and Inhibins: Roles in Development, Physiology, and Disease

A Key Role for Inhibins in Dendritic Cell Maturation and Function

Contact Info

Product

Resources

About