George R. Bousfield

Wichita State University

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Viktor Y. Butnev

Wichita State University

Vladimir Y. Butnev

Wichita State University

Jeffrey V. May

Wichita State University

Kim Jonas

King's College London

James A. Dias

University at Albany, State University of New York

David J. Harvey

University of Oxford

Darrell N. Ward

The University of Texas MD Anderson Cancer Center

Alfredo Ulloa‐Aguirre

Universidad Nacional Autónoma de México

William T. Moore

Liberty University

John S. Davis

University of Nebraska Medical Center

Cooperative Institutions

Wichita State University

University of Kansas

Emporia State University

Centre National de la Recherche Scientifique

University of Nebraska Medical Center

Benedictine College

Kansas State University

Fort Hays State University

Washburn University

Universidad Nacional Autónoma de México

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Comparative binding of FSH to chicken and rat testis

Journal of Endocrinological Investigation (1989)

Wayne L. Gordon George R. Bousfield D N Ward

Testicle

10.1007/bf03350707

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Citations (15)

Identification of the rat bone 60K acidic glycoprotein as α2HS-glycoprotein

Bone and Mineral (1991)

Morimichi Mizuno Mary C. Farach‐Carson Gerald J. Pinero Ryuichi Fujisawa Jan C. Brunn

Polyclonal antibodies

10.1016/0169-6009(91)90046-3

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Citations (41)

Differential follicle stimulating hormone glycosylation modulates pre-antral follicle growth and survival rates

Endocrine Abstracts (2021)

Gillian M. Johnson Caitlan G A Onabanjo George R. Bousfield Kate Hardy Kim Jonas

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Antral follicle

10.1530/endoabs.77.oc1.6

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Citations (0)

Hypo‐glycosylated Human Follicle–Stimulating Hormone (hFSH ²¹ ) Exhibits Higher Endocytic Rate for Recombinant hFSH Receptor than Fully‐glycosylated hFSH (hFSH ²⁴ )

The FASEB Journal (2015)

Ramy Elsaid Vladimir Butnev Viktor Y. Butnev Jeffrey V. May George R. Bousfield

Follicle-stimulating hormone (FSH) plays an essential role in the regulation of reproduction, as FSH KO female mice are sterile. FSH regulates ovarian granulosa and testicular Sertoli cell function by binding to its cognate receptor (FSHR), a member of the G protein-coupled receptor family. Human FSH exists as a heterogeneous mixture of glycoform, differing in the number and location of β subunit glycans. Recently, it has been reported that hypo-glycosylated hFSH binds and activates hFSHR more than fully-glycosylated hFSH (Bousfield et al. Molecular and Cellular Endocrinology 382: 989-997, 2013). We analyzed the kinetics of FSH/FSH receptor complex endocytosis using 125I-hFSH21, 125I-hFSH24 glycoform tracers and recombinant hFSHR-expressing Chinese Hamster Ovarian (CHO) cells as a model system. A greater endocytic rate for hypo-glycosylated hFSH/FSH receptor complex was observed than for fully-glycosylated hFSH/FSH receptor complex. One could argue that this reflects greater receptor occupancy for hFSH21. However, increased FSH binding induced by non-steroidal allosteric modulators of the FSHR, is not attended by increased internalization. Hypo-glycosylated hFSH21 can not only occupy more FSHR binding sites, but also more effectively activates these receptors and this appears to increase the internalization rate. Supported by NIH grant 5P01 AG-029531.

Follicle-stimulating hormone receptor

Internalization

Granulosa cell

10.1096/fasebj.29.1_supplement.890.8

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Citations (0)

Hybrids from equine LH: alpha enhances, beta diminishes activity

Molecular and Cellular Endocrinology (1985)

George R. Bousfield Wan-Kyng Liu Darrell N. Ward

Alpha (finance)

BETA (programming language)

10.1016/0303-7207(85)90159-5

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Citations (27)

Structural features of mammalian gonadotropins

Molecular and Cellular Endocrinology (1996)

George R. Bousfield Viktor Y. Butnev Russell Gotschall Vanda L. Baker William T. Moore

Gonadotropin

Alpha (finance)

10.1016/s0303-7207(96)03945-7

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Citations (112)

In Vitro Impact of FSH Glycosylation Variants on FSH Receptor-stimulated Signal Transduction and Functional Selectivity

Journal of the Endocrine Society (2020)

Teresa Zariñán Viktor Y. Butnev Rubén Gutiérrez‐Sagal José Luis Maravillas‐Montero Iván Martínez-Luis

Abstract FSH exists as different glycoforms that differ in glycosylation of the hormone-specific β-subunit. Tetra-glycosylated FSH (FSH24) and hypo-glycosylated FSH (FSH18/21) are the most abundant glycoforms found in humans. Employing distinct readouts in HEK293 cells expressing the FSH receptor, we compared signaling triggered by human pituitary FSH preparations (FSH18/21 and FSH24) as well as by equine FSH (eFSH), and human recombinant FSH (recFSH), each exhibiting distinct glycosylation patterns. The potency in eliciting cAMP production was greater for eFSH than for FSH18/21, FSH24, and recFSH, whereas in the ERK1/2 activation readout, potency was highest for FSH18/21 followed by eFSH, recFSH, and FSH24. In β-arrestin1/2 CRISPR/Cas9 HEK293-KO cells, FSH18/21 exhibited a preference toward β-arrestin-mediated ERK1/2 activation as revealed by a drastic decrease in pERK during the first 15-minute exposure to this glycoform. Exposure of β-arrestin1/2 KO cells to H89 additionally decreased pERK1/2, albeit to a significantly lower extent in response to FSH18/21. Concurrent silencing of β-arrestin and PKA signaling, incompletely suppressed pERK response to FSH glycoforms, suggesting that pathways other than those dependent on Gs-protein and β-arrestins also contribute to FSH-stimulated pERK1/2. All FSH glycoforms stimulated intracellular Ca2+ (iCa2+) accumulation through both influx from Ca2+ channels and release from intracellular stores; however, iCa2+ in response to FSH18/21 depended more on the latter, suggesting differences in mechanisms through which glycoforms promote iCa2+ accumulation. These data indicate that FSH glycosylation plays an important role in defining not only the intensity but also the functional selectivity for the mechanisms leading to activation of distinct signaling cascades.

Follicle-stimulating hormone receptor

HEK 293 cells

10.1210/jendso/bvaa019

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Citations (26)

Oocyte quality is enhanced by hypoglycosylated FSH through increased cell-to-cell interaction during mouse follicle development

Development (2023)

Aubrey Converse Zhenghui Liu Jai Chand Patel Sushil Kumar Shakyawar Chittibabu Guda

Macroheterogeneity in follicle-stimulating hormone (FSH) β-subunit N-glycosylation results in distinct FSH glycoforms. Hypoglycosylated FSH21 is the abundant and more bioactive form in pituitaries of females under 35 years of age, whereas fully glycosylated FSH24 is less bioactive and increases with age. To investigate whether the shift in FSH glycoform abundance contributes to the age-dependent decline in oocyte quality, the direct effects of FSH glycoforms on folliculogenesis and oocyte quality were determined using an encapsulated in vitro mouse follicle growth system. Long-term culture (10-12 days) with FSH21 (10 ng/ml) enhanced follicle growth, estradiol secretion and oocyte quality compared with FSH24 (10 ng/ml) treatment. FSH21 enhanced establishment of transzonal projections, gap junctions and cell-to-cell communication within 24 h in culture. Transient inhibition of FSH21-mediated bidirectional communication abrogated the positive effects of FSH21 on follicle growth, estradiol secretion and oocyte quality. Our data indicate that FSH21 promotes folliculogenesis and oocyte quality in vitro by increasing cell-to-cell communication early in folliculogenesis, and that the shift in in vivo abundance from FSH21 to FSH24 with reproductive aging may contribute to the age-dependent decline in oocyte quality.

10.1242/dev.202170

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Citations (7)

Bioactivity of recombinant hFSH glycosylation variants in primary cultures of porcine granulosa cells

Molecular and Cellular Endocrinology (2020)

Aixin Liang Michele R. Plewes Guohua Hua Xiaoying Hou Haley R Blum

Granulosa cell

INHA

10.1016/j.mce.2020.110911

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Citations (13)

Follicle-Stimulating Hormone Glycobiology

Endocrinology (2019)

George R. Bousfield David J. Harvey

FSH glycosylation varies in two functionally important aspects: microheterogeneity, resulting from oligosaccharide structure variation, and macroheterogeneity, arising from partial FSHβ subunit glycosylation. Although advances in mass spectrometry permit extensive characterization of FSH glycan populations, microheterogeneity remains difficult to illustrate, and comparisons between different studies are challenging because no standard format exists for rendering oligosaccharide structures. FSH microheterogeneity is illustrated using a consistent glycan diagram format to illustrate the large array of structures associated with one hormone. This is extended to commercially available recombinant FSH preparations, which exhibit greatly reduced microheterogeneity at three of four glycosylation sites. Macroheterogeneity is demonstrated by electrophoretic mobility shifts due to the absence of FSHβ glycans that can be assessed by Western blotting of immunopurified FSH. Initially, macroheterogeneity was hoped to matter more than microheterogeneity. However, it now appears that both forms of carbohydrate heterogeneity have to be taken into consideration. FSH glycosylation can reduce its apparent affinity for its cognate receptor by delaying initial interaction with the receptor and limiting access to all of the available binding sites. This is followed by impaired cellular signaling responses that may be related to reduced receptor occupancy or biased signaling. To resolve these alternatives, well-characterized FSH glycoform preparations are necessary.

Glycobiology

Oligosaccharide

10.1210/en.2019-00001

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Citations (36)