Betaglycan (TGFBR3) Functions as an Inhibin A, but Not Inhibin B, Coreceptor in Pituitary Gonadotrope Cells in Mice

Li, Yining; Fortin, Jérôme; Ongaro, Luisina; Zhou, Xiang; Boehm, Ulrich; Schneyer, Alan L.; Bernard, Daniel J.; Lin, Herbert Y.

doi:10.1210/en.2018-00770

Cited by 44 publications

(61 citation statements)

References 56 publications

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“…In adulthood, Sertoli cells are meiotically inactive. [28][29][30] Sertoli cell division terminates concurrently with the first meiotic division of the germ cells, giving rise to tight junctions between these cells, known as the Blood-Testis Barrier (BTB) ( Figure 2). 31,32 The epithelium of seminiferous tubules is divided into two (functionally different) regions by BTB.…”

Section: Male's Reproductive Organmentioning

confidence: 99%

<p>Some of the Factors Involved in Male Infertility: A Prospective Review</p>

Babakhanzadeh

Nazari

Ghasemifar

2020

IJGM

178

101

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Infertility is defined as the inability of couples to have a baby after one year of regular unprotected intercourse, affecting 10 to 15% of couples. According to the latest WHO statistics, approximately 50-80 million people worldwide sufer from infertility, and male factors are responsible for approximately 20-30% of all infertility cases. The diagnosis of infertility in men is mainly based on semen analysis. The main parameters of semen include: concentration, appearance and motility of sperm. Causes of infertility in men include a variety of things including hormonal disorders, physical problems, lifestyle problems, psychological issues, sex problems, chromosomal abnormalities and single-gene defects. Despite numerous efforts by researchers to identify the underlying causes of male infertility, about 70% of cases remain unknown. These statistics show a lack of understanding of the mechanisms involved in male infertility. This article focuses on the histology of testicular tissue samples, the male reproductive structure, factors affecting male infertility, strategies available to find genes involved in infertility, existing therapeutic methods for male infertility, and sperm recovery in infertile men.

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Section: Male's Reproductive Organmentioning

confidence: 99%

<p>Some of the Factors Involved in Male Infertility: A Prospective Review</p>

Babakhanzadeh

Nazari

Ghasemifar

2020

IJGM

178

101

View full text Add to dashboard Cite

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“…One interpretation of these data is that we did not sample females at the appropriate cycle stage to observe effects of the gene deletion on FSH. Though we collected blood and pituitaries on the morning of estrus, it was a few hours after the peak of the secondary surge (Li et al 2018a). Nonetheless, litter size is normal, arguing against an impairment in FSH production at any cycle stage.…”

Section: Journal Of Endocrinologymentioning

confidence: 99%

Impaired LH surge amplitude in gonadotrope-specific progesterone receptor knockout mice

Toufaily

Schang

Zhou

et al. 2020

Journal of Endocrinology

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The progesterone receptor (PR, encoded by Pgr) plays essential roles in reproduction. Female mice lacking the PR are infertile, due to the loss of the protein’s functions in the brain, ovary, and uterus. PR is also expressed in pituitary gonadotrope cells, but its specific role therein has not been assessed in vivo. We therefore generated gonadotrope-specific Pgr conditional knockout mice (cKO) using the Cre-LoxP system. Overall, both female and male cKO mice appeared phenotypically normal. cKO females displayed regular estrous cycles (vaginal cytology) and normal fertility (litter size and frequency). Reproductive organ weights were comparable between wild-type and cKO mice of both sexes, as were production and secretion of the gonadotropins, LH and FSH, with one exception. On the afternoon of proestrus, the amplitude of the LH surge was blunted in cKO females relative to controls. Contrary to predictions of earlier models, this did not appear to derive from impaired GnRH self-priming. Collectively, these data indicate that PR function in gonadotropes may be limited to regulation of LH surge amplitude in female mice via a currently unknown mechanism.

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“…Since inhibin’s biological functions have been shown to be dependent on the coreceptors TGFBR3 and ENG [ 24 , 27 , 118 – 121 ], we examined the impact of INHA based on the expression levels of each of the co-receptor ( Table 1 ). In this analysis, we find that that when separating patients into high or low expressing TGFBR3 or ENG groups ( Table 1 ) in p53 mutated breast cancers, where INHA is a negative predictor of survival in all patients ( Fig 2 ), INHA was only a predictor of poor survival in patients with low TGFBR3 (HR = 2.29, p = 0.015) or low ENG (HR = 2.24, p = 0.035).…”

Section: Resultsmentioning

confidence: 99%

A bioinformatic analysis of the inhibin-betaglycan-endoglin/CD105 network reveals prognostic value in multiple solid tumors

et al. 2021

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Inhibins and activins are dimeric ligands belonging to the TGFβ superfamily with emergent roles in cancer. Inhibins contain an α-subunit (INHA) and a β-subunit (either INHBA or INHBB), while activins are mainly homodimers of either βA (INHBA) or βB (INHBB) subunits. Inhibins are biomarkers in a subset of cancers and utilize the coreceptors betaglycan (TGFBR3) and endoglin (ENG) for physiological or pathological outcomes. Given the array of prior reports on inhibin, activin and the coreceptors in cancer, this study aims to provide a comprehensive analysis, assessing their functional prognostic potential in cancer using a bioinformatics approach. We identify cancer cell lines and cancer types most dependent and impacted, which included p53 mutated breast and ovarian cancers and lung adenocarcinomas. Moreover, INHA itself was dependent on TGFBR3 and ENG/CD105 in multiple cancer types. INHA, INHBA, TGFBR3, and ENG also predicted patients’ response to anthracycline and taxane therapy in luminal A breast cancers. We also obtained a gene signature model that could accurately classify 96.7% of the cases based on outcomes. Lastly, we cross-compared gene correlations revealing INHA dependency to TGFBR3 or ENG influencing different pathways themselves. These results suggest that inhibins are particularly important in a subset of cancers depending on the coreceptor TGFBR3 and ENG and are of substantial prognostic value, thereby warranting further investigation.

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Betaglycan (TGFBR3) Functions as an Inhibin A, but Not Inhibin B, Coreceptor in Pituitary Gonadotrope Cells in Mice

Cited by 44 publications

References 56 publications

<p>Some of the Factors Involved in Male Infertility: A Prospective Review</p>

<p>Some of the Factors Involved in Male Infertility: A Prospective Review</p>

Impaired LH surge amplitude in gonadotrope-specific progesterone receptor knockout mice

A bioinformatic analysis of the inhibin-betaglycan-endoglin/CD105 network reveals prognostic value in multiple solid tumors

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