Ontogenesis of somatomedin and insulin receptors in the human fetus.

Sara, Vicki R.; Hall, Kerstin; Misaki, Moriharu; Fryklund, Linda; Christensen, N. J.; Wetterberg, Lennart

doi:10.1172/jci110858

Cited by 198 publications

(76 citation statements)

References 30 publications

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“…These correlations are expected from the findings of increased serum IGFBP-1 and IGFBP-2 levels by Western ligand blotting and decreased IGF-I in IUGR newborns (21,27,43). IGF-I has been reported to inhibit IGFBP-1 production in Hep G-2 cells (51), which, similar to the fetal liver but unlike the adult liver, display high expression of the type 1 IGF receptor (2,52). Because the fetal human liver is the major production site for IGFBP-1 and IGFBP-2 (14, 15), IGF-I may regulate their expression in the human fetus.…”

Section: Discussionmentioning

confidence: 99%

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Ontogeny of Insulin-Like Growth Factor-Binding Protein-1, −2, and −3: Quantitative Measurements by Radioimmunoassay in Human Fetal Serum

et al. 1994

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Section: Discussionmentioning

confidence: 99%

“…IGF-I and IGF-I1 are important paracrinelautocrine fetal growth factors with potential actions a s early as during human embryogenesis (1)(2)(3)(4)(5). In addition, IGF-I may be an important endocrine growth factor regulating generalized…”

mentioning

confidence: 99%

Ontogeny of Insulin-Like Growth Factor-Binding Protein-1, −2, and −3: Quantitative Measurements by Radioimmunoassay in Human Fetal Serum

et al. 1994

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“…We also have found that a synthetic human H1 relaxin analog (deletion of the C-terminal Lys-Arg-Ser-Leu of B chain) could displace the binding of 32P-relaxin with a dissociation constant very similar to that of H2 relaxin (unpublished results of PLO). The crossreactive binding of these peptide hormones to other members of the receptor family raises the possibility that relaxin may display tissue-specific binding to additional receptor(s), possibly of the insulin receptor family (34)(35)(36)(37)(38), with either higher or lower affinities. Thus, the discovery of these relaxin binding sites in the brain and heart may uncover a complex biology in several organ systems.…”

Section: Discussionmentioning

confidence: 99%

Relaxin binding in the rat heart atrium.

Osheroff¹,

Cronin²,

Lofgren³

1992

Proc. Natl. Acad. Sci. U.S.A.

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Relaxin is a member of the insulin family of polypeptides that is best known as a reproductive hormone. In an effort to elucidate the mechanism of action of relaxin we previously localized the specific binding sites of a 32P-labeled relaxin in the rat uterus and brain. These studies suggested that, in addition to its classical role in pregnancy, relaxin might have other physiological functions. In the present paper we describe the specific and high-afminity binding of relaxin to the cardiac atrium of both male and female rats. The relaxin binding could not be displaced by peptides belonging to the same family [insulin, insulin-like growth factor I (IGF-I)] or by peptides that were identified in the atrium or were known to have cardiovascular functions (atrial natriuretic peptide, angiotensin II). The dissociation constant for relaxin in the atrium was estimated to be 1.4 nM, which was similar to that found in the uterus (1.3 nM) and the brain (1.4 nM). In view of the close association of relaxin with reproduction, an experiment was also performed to compare the relaxin binding in the uterus and heart after gonadectomy and sex steroid treatment. It was found that the relaxin binding in the rat uterus was diminished by 53% overall following ovariectomy but was restored to 90% of normal levels when treated with estrogen (but not with testosterone). In contrast, the relaxin binding in the rat heart was not affected by castration or sex steroid treatment. We conclude that specific and high-affinity relaxin receptors exist in the atrium of both the male and female rat heart and that these are regulated differently than the relaxin receptors in the uterus.Relaxin is structurally related to insulin and insulin-like growth factors and is best known as a pregnancy-associated hormone (1, 2). In addition to its classical actions on cervical ripening, uterine contraction, and pubic symphysis elongation (1, 2), relaxin has been suggested to participate in the regulation of blood pressure (3-8) and neuropeptide release, notably oxytocin and vasopressin (9-13). However, the results from these studies were conflicting, and the site of action of relaxin was undetermined. Biochemical support for these hypotheses was provided when it was shown that, in addition to the uterus and cervix (14), relaxin bound with specificity and high affinity (Kd 1 nM) to several sites in the male and female rat brain (15). Some of these sites, in particular two of the circumventricular organs (subfornical organ and organum vasculosum of the lamina terminalis) and the magnocellular hypothalamic nuclei (paraventricular and supraoptic nucleus) are known to be involved in the control of blood pressure, fluid balance, and the release of neuropeptides. To further investigate the mechanism of action of relaxin, we continued the search for relaxin target tissues and were surprised to observe the specific and high-affinity binding of relaxin to the atrium of the rat heart. We also show that the atrial binding is regulated differently than the uterus. ...

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“…Receptors for IGF-I are found in various tissues early in gestation (3), and fetal tissues seem to have enhanced sensitivity to IGF-I compared with later in life (4). Using cordocenteses, it has been possible to determine the "normal" range of IGF-I in fetal serum and to define a positive correlation between serum concentration of IGF-I and gestational age (5)(6)(7)(8)(9)(10).…”

mentioning

confidence: 99%