Purified human α-fetoprotein inhibits follicle-stimulating hormone-stimulated estradiol production by porcine granulosa cells in culture

Keel, Brooks A.; Eddy, Kevan B.; Gangrade, Bhushan K.; May, Jeffrey V.

doi:10.1016/0303-7207(93)90047-n

Cited by 9 publications

(6 citation statements)

References 14 publications

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“…The results obtained by Keel et al [49][50][51] showing that, depending on the nature of the associated growth factors, AFP can act on cell multiplication or differentiation are particu larly interesting. Nevertheless, the role of the various fatty acids bound to AFP must now be evaluated in these experiments considering the results of Bandhyopadyay [53] indicating that fatty acids intervene to potentiate the effect of some growth factors.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, very interesting studies on the differentiation and multiplication of estro gen-producing and estrogen-sensitive cells have been published [49][50][51]. These studies in two apparently independent domains are an example of how a multidomain synthesis can aid in revitalizing our thinking and our exper imental strategies to better understand the biological roles of AFP.…”

Section: Regardless O F the Mechanisms Proposed In Points I And 2 Efmentioning

confidence: 99%

“…The studies of Keel et al [49][50][51] show that transforming growth factor a stimulates basal estradiol production by porcine granulosa cells (Pgc) in culture. Physiological concentra tions of purified AFP significantly and dosedependently inhibit growth-factor-stimulated estradiol production by Pgc.…”

Section: Regardless O F the Mechanisms Proposed In Points I And 2 Efmentioning

confidence: 99%

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Biological Role of Alpha-Fetoprotein in the Endocrinological Field: Data and Hypotheses

Nunez¹

1994

Tumor Biol

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α-Fetoprotein (AFP), depending on the surrounding conditions, exerts different functions by different mechanisms. (1) A regulatory effect on the concentration of the unbound form of its various ligands (e.g. fatty acids, estrogens, phytosteroids). Thus, numerous studies have demonstrated that fatty acids, particularly the polyunsaturated fatty acids, modulate positively or negatively many steps of the action of various steroids and many enzymes involved in the transduction of membrane-triggered signals. (2) Different conformations (holoforms) of AFP, depending on the nature and concentration of the ligand(s) bound, might influence the binding of the protein to specific receptor(s) and as a consequence its biological properties (internalization, action on the membrane signal transduction pathway). (3) Regardless of the mechanisms, proposed in points 1 and 2, the protein can exert effects associated with other signals such as growth factors. The nature of the associated growth factor(s) and AFP ligand(s) can orient cells towards multiplication or differentiation.

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Section: Discussionmentioning

confidence: 99%

Section: Regardless O F the Mechanisms Proposed In Points I And 2 Efmentioning

confidence: 99%

Section: Regardless O F the Mechanisms Proposed In Points I And 2 Efmentioning

confidence: 99%

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Biological Role of Alpha-Fetoprotein in the Endocrinological Field: Data and Hypotheses

Nunez¹

1994

Tumor Biol

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“…Subsequent use of the granulosal cell cultures seemed to indicate that, while HAFP was capable of growth factor-enhanced growth of these cells in vitro, HAFP also inhibited the steroidogenic function of E2 production (Keel et al, 1992). It was later demonstrated that HAFP actually inhibited the FSHstimulated E2 production in the porcine granulosa cells (Keel, 1993). Those authors suggested that AFP could be inhibiting differentia-ted functions such as aromatase enzyme activity while enhancing cell proliferation.…”

Section: G) Afp Peptide Sites For Hormones and Growth Factor Bindingmentioning

confidence: 99%

Mapping of Structure-Function Peptide Sites on the Human Alpha-fetoprotein Amino Acid Sequence

Mizejewski¹

2011

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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The structure of alpha-fetoprotein (AFP) is presen-ted in light of AFP membership and position in the albuminoid gene family in comparison to other gene family members. Ontogenetic AFP gene expression is reviewed considering AFP mRNA presence in various tissues at different times during development. The multiple molecular variant forms of AFP are discussed in relation to published reports of AFP binding proteins and cell surface receptors. The atlas further shows AFP as a protein consisting of multiple peptide-cassettes consisting of amino acid (AA) sequence stretches matched to peptide segments on prohormones and biological response modifier proteins. Such AFP peptide segments could potentially serve as delivery agents which could target vascular, neuroendocrine, or gastrointestinal cells. A discussion follows in which peptide epitopes, extracellular matrix proteins, serine proteases, extracellular matrix, and cellular adhesion AA identity sites on AFP are considered. The AFP molecule is also viewed as a carrier/ transport protein based on AA sequence comparison of various proteins that bind hydropho-bic ligands and heavy metals similar to AFP binding of such components. An analysis of trans-cription factors, tumor suppressors, and AA-rich motifs follows, interfaced with dimerization and nuclear localization sequence matches identified on the AFP molecule. Emphasis is further placed upon homeodomain and apoptosis AA sequence identi-ties given that AFP serves as a fetal, phasespecific protein throughout embryogenesis, histogenesis, and organogenesis. AFP AA sequences are further presented as peptide identification sites for Mapping of Structure-Function Peptide Sites on the Human Alpha-fetoprotein Amino Acid SequenceMizejewski GJ Atlas Genet Cytogenet Oncol Haematol. 2010; 14(2) 170 growth factors, receptors, cytoskeletal proteins, and chemo-kines. A closing discussion summarizes the multi-ple and varied motifs of peptide sequences matched to AAs on each of AFP's three domains. This study indicates that short peptide segments, in addition to full-length AFP, and domain and subdomain fragments of AFP, could be employed as functional agents to help unravel the complexity of biological roles ascribed to human AFP.

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“…It may be of interest that a PDGF receptor-like sequence has been detected on the first domain of HAFP (see "AFP and Programmed Cell Death" above). Subsequent use of the granulosal cell cultures seemed to indicate that, while HAFP was capable of growth factor-enhanced growth of these cells in vitro, HAFP also inhibited the steroidogenic function of E2 production (220). It was later demonstrated that HAFP actually inhibited the FSHstimulated E2 production in the porcine granulosa cells (221).…”

Section: Ligand Binding and Carrierrransportmentioning

confidence: 97%

-Fetoprotein as a Biologic Response Modifier: Relevance to Domain and Subdomain Structure

1997

Experimental Biology and Medicine

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In the present review, the structure of alpha-fetoprotein (AFP) is discussed in consideration of AFP membership and position in the albuminoid supergene family in relation to other gene family members. Ontogenetic AFP gene expression is then discussed in view of AFP mRNA presence in various tissues at different times during development. The multiple molecular forms of AFP is also presented in relation to published reports of AFP binding proteins and cell surface receptors. The review proceeds on to present AFP as a potential model of a modular/cassette protein based on sequence comparison with cleaved fragments of prohormones and biological response modifiers. Such cleaved fragments could potentially serve as peptide messengers for vascular, neuroendocrine, and digestive biological activities. Following a discussion on fibrin binding and serine proteases, AFP-cytoskeletal, extracellular matrix, and cellular adhesion interactions are considered. AFP as a carrier/transport protein based on structural relationships is further elucidated by examination of the various ligands bound to AFP and its hormone interaction. Since AFP binds heavy metals, the question is posed of whether AFP could function as an antioxidant. An analysis of transcription factors, tumor suppressors, and homeodomain proteins follows, which is interfaced with the concept of programmed cell death in light of amino acid sequence matches detected on the AFP molecule. Emphasis was naturally placed upon the homeodomain protein sequence stretches since AFP is a fetal, phase-specific protein found throughout embryogenesis, histogenesis, and organogenesis. In keeping with histogenesis, a discussion of AFP and eye lens protein development is presented. Finally, AFP sequence analysis presented in light of members of the immunoglobulin superfamily, autoimmune disorders, and various disease states culminates the review. A closing discussion then summarizes regions of presumptive matched protein identities on each of AFP's three domains.

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Purified human α-fetoprotein inhibits follicle-stimulating hormone-stimulated estradiol production by porcine granulosa cells in culture

Cited by 9 publications

References 14 publications

Biological Role of Alpha-Fetoprotein in the Endocrinological Field: Data and Hypotheses

Biological Role of Alpha-Fetoprotein in the Endocrinological Field: Data and Hypotheses

Mapping of Structure-Function Peptide Sites on the Human Alpha-fetoprotein Amino Acid Sequence

-Fetoprotein as a Biologic Response Modifier: Relevance to Domain and Subdomain Structure

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