Gonadotropins

Ulloa‐Aguirre, Alfredo; Dias, James A.; Bousfield, George R.

doi:10.1007/978-3-319-44441-3_3

Cited by 6 publications

(4 citation statements)

References 283 publications

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“…The oligosaccharide structure confers distinctly different physiological features such as plasma half-life and potency at the target cell level ( 38 , 81 ). As previously mentioned, oligosaccharide heterogeneity exists in two forms, microheterogeneity, which results from variation in the type of carbohydrates comprising the oligosaccharides attached to the protein core ( 38 ), and macroheterogeneity, which comes from the absence of one or more oligosaccharide chains from a hormone variant ( 11 ).…”

Section: Naturally Occurring Glycoforms: Challenging the Future Of Follitropin Administration In The Clinical Arenamentioning

confidence: 99%

“…(B) In pituitary FSH the most abundant types of glycan are the triantennary type. Two alternatives exist ( 11 ): a. all three Neu5Ac residues can be linked α2–3; b. alternatively, there can be 2 linked α2–6 and one linked α2–3. The one α2–3 linked Neu5Ac on the Galβ1-4GlcNAcβ1-2Manα1-3 branch ( right ) was arbitrarily placed.…”

Section: Introductionmentioning

confidence: 99%

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New Human Follitropin Preparations: How Glycan Structural Differences May Affect Biochemical and Biological Function and Clinical Effect

Dias

Ulloa‐Aguirre

2021

Front. Endocrinol.

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It is well accepted that pituitary follitropin is secreted into the circulation as a mixture of variants, which differ not in primary structure but rather at the level of glycosylation. These glycosidic forms vary in the number of glycosylation sites filled, complexity of glycosidic chains, and sialylation and sulfation. It is generally agreed that high sialylation, 2,3 sialic acid capping of terminal N-acetyl galactosamine or galactose leads to longer circulating half-life, by blocking binding of asialoglycoprotein receptor (ASGPR) in the liver. In contrast, 2,6 sialic acid found in humans does not prevent recognition of galactose and N-acetyl galactosamine by ASGPR. Few studies on clinical outcomes comparing differences in sialylation of follitropin found in commercially available preparations are available. Thus, there is a clear need for a consortium of open data to address this unmet need. Recently, FSH glycosylation, primarily on the β-subunit, which varies as women age, has emerged as a key modifier of follitropin action, with profound biological effects in vivo in animal models. To date, limited information of recombinant follitropin hormone preparations is available. Thus, most of the studies with FSH that is well characterized biochemically have been done in vitro, with engineered non gonadal host cells bearing recombinant receptors or in animal models. Since limited studies in human granulosa cells are available, a question is whether structural differences in glycosylation in commercially available follitropin affects biological function and clinical effect in humans. The presence of fucose, for example, has not been studied greatly even though, in the case of antibody therapy it has been shown to have a large effect on antibody targeting. This review on glycosidic variability of follitropin from the biochemical/structural point of view reflects on this question and presents an assessment in the context of available published data. If clinical differences are to be expected or not, the readers will have a better understanding of the evidence for and limitations of such expectations.

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Section: Naturally Occurring Glycoforms: Challenging the Future Of Follitropin Administration In The Clinical Arenamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

New Human Follitropin Preparations: How Glycan Structural Differences May Affect Biochemical and Biological Function and Clinical Effect

Dias

Ulloa‐Aguirre

2021

Front. Endocrinol.

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“…Follicle stimulating hormone (FSH) is a pituitary‐derived heterodimeric glycoprotein that plays critical roles in the male reproduction. FSH binds to G‐protein coupled receptors (FSHRs), exclusively expressed on Sertoli cells within the testis 6,7 . In vitro and in vivo studies using several species indicate that in response to FSH signaling, Sertoli cells proliferate only during a narrow window of time postnatally in the mouse testis.…”

Section: Introductionmentioning

confidence: 99%

“…FSH binds to G-protein coupled receptors (FSHRs), exclusively expressed on Sertoli cells within the testis. 6,7 In vitro and in vivo studies using several species indicate that in response to FSH signaling, Sertoli cells proliferate only during a narrow window of time postnatally in the mouse testis. Thereafter, they become post-mitotic and undergo terminal differentiation.…”

Section: Introductionmentioning

confidence: 99%

Identification of follicle‐stimulating hormone‐responsive genes in Sertoli cells during early postnatal mouse testis development

et al. 2023

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Background: In the mouse testis, Sertoli cells rapidly divide during a narrow window of time pre-pubertally and differentiate thereafter. The number of Sertoli cells determines the testis size and germ cell-carrying capacity. Follicle-stimulating hormone (FSH) binds its cognate FSH-receptors expressed on Sertoli cells and acts as a mitogen to regulate their proliferation. Fshb −/− mutant adult male mice have reduced Sertoli cell number and testis size and reduced sperm number and motility. However, FSH-responsive genes in early postnatal mouse Sertoli cells are unknown.Objectives: To identify FSH-responsive genes in early postnatal mouse Sertoli cells. Materials and methods:A fluorescence-activated cell sorting method was developed to rapidly purify Sertoli cells from control and Fshb −/− mice carrying a Sox9 GfpKI allele.These pure Sertoli cells were used for large-scale gene expression analyses. Results: We show that mouse Sertoli cells rarely divide beyond postnatal day 7. Our in vivo BrdU labeling studies indicate loss of FSH results in a 30% reduction in Sertoli cell proliferation in mice at 5 days of age. Flowsorted GFP + Sertoli cells with maximal Fshr expression were 97%-98% pure and mostly devoid of Leydig and germ cells as assessed by Taqman qPCR quantification of gene expression and immunolabeling of the corresponding cell-specific markers. Large-scale gene expression analysis identified several differentially regulated genes in flow-sorted GFP + Sertoli cells obtained from testis of control and Fshb −/− mice at 5 days of age. The top 25 networks identified by pathway analysis include those related to the cell cycle, cell survival and most importantly, carbohydrate and lipid metabolism and molecular transport. Discussion: Several of the FSH-responsive genes identified in this study could serve as useful markers for Sertoli cell proliferation in normal physiology, toxicant-induced Sertoli cell/testis injury, and other pathological conditions. Conclusion:Our studies reveal that FSH-regulates macromolecular metabolism and molecular transport networks of genes in early postnatal Sertoli cells most likely in preparation for establishment of functional associations with germ cells to successfully coordinate spermatogenesis.

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Effect of LHCGR and FSHR gene polymorphisms on fertility traits and milk yield of cross-bred dairy cows in Sri Lanka

Abeygunawardana

Ranasinghe

Silva

et al. 2022

Animal Biotechnology

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Gonadotropins

Cited by 6 publications

References 283 publications

New Human Follitropin Preparations: How Glycan Structural Differences May Affect Biochemical and Biological Function and Clinical Effect

New Human Follitropin Preparations: How Glycan Structural Differences May Affect Biochemical and Biological Function and Clinical Effect

Identification of follicle‐stimulating hormone‐responsive genes in Sertoli cells during early postnatal mouse testis development

Effect of LHCGR and FSHR gene polymorphisms on fertility traits and milk yield of cross-bred dairy cows in Sri Lanka

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