hCGbeta core fragment is a metabolite of hCG: evidence from infusion of recombinant hCG

Norman, Robert J.; Buchholz, MM; Somogyi, A.; Amato, F.

doi:10.1677/joe.0.1640299

Cited by 25 publications

(15 citation statements)

References 23 publications

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“…hCG cf is quantitatively the major form of immunoreactive hCG molecules in pregnancy urine, the concentration of which is 2 to10 times higher than that of intact hCG on a molar basis (Kato & Braunstein 1988, Wehmann et al 1990, de Medeiros et al 1992, and it has been assumed that hCG cf originates from the renal metabolism of intact hCG or free hCG (Wehmann & Nisula 1980, Lefort et al 1984, 1986. However, in a study involving the intravenous injection of recombinant hCG into healthy, non-pregnant women, the hCG cf measured in urine was only 12·2% of the amount of hCG excreted in urine, and it was suggested that there may be more than one pathway responsible for the production of hCG cf in pregnancy (Norman et al 2000). In fact, placental tissue has been associated with the production of hCG cf (Cole & Birken 1988, Udagawa et al 1998.…”

Section: Introductionmentioning

confidence: 99%

Human chorionic gonadotropin (hCG) beta-core fragment is produced by degradation of hCG or free hCG beta in gestational trophoblastic tumors: a possible marker for early detection of persistent postmolar gestational trophoblastic disease

Okamoto

Matsuo²,

Niu³

et al. 2001

Journal of Endocrinology

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The present study was undertaken to investigate whether human chorionic gonadotropin (hCG) -core fragment (hCG cf) was directly produced by gestational trophoblastic tumors. Immunoreactivity of hCG cf was demonstrated in the extracts as well as in the culture media of hydatidiform mole tissues. It was also present in the extracts of choriocarcinoma tissues, and its molar concentration exceeded that of intact hCG. The presence of hCG cf was then confirmed by gel chromatography and Western blot analysis. Immunohistochemistry showed localization of hCG cf immunoreactivity to the syncytiotrophoblasts and scattered cells in the stroma of mole tissue, and to syncytiotrophoblastic cells in choriocarcinoma. Immunoreactivity of hCG cf was also detected in the sera of the patients with gestational trophoblastic disease, although the hCG cf/hCG ratio was less than one hundredth of that in the tissue extracts. Serial measurement of serum hCG cf levels after mole evacuation showed that they declined much more rapidly than those of hCG and became undetectable in the patients with subsequent spontaneous resolution, while hCG cf remained or became detectable before the rise of hCG was observed in the patients with subsequent persistent trophoblastic disease. Taken together, these results suggest that hCG cf is directly produced by gestational trophoblastic tumors, and monitoring of hCG cf in the serum after mole evacuation may be useful for early prediction of subsequent development of postmolar persistent trophoblastic disease.

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Section: Introductionmentioning

confidence: 99%

Human chorionic gonadotropin (hCG) beta-core fragment is produced by degradation of hCG or free hCG beta in gestational trophoblastic tumors: a possible marker for early detection of persistent postmolar gestational trophoblastic disease

Okamoto

Matsuo²,

Niu³

et al. 2001

Journal of Endocrinology

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“…There is considerable evidence, based on clearance studies, that the hCG cf is produced by kidney degradation of circulating hCG (Wehmann et al 1984). A new study using infusion of recombinant hCG reinforces the origin of hCG cf by kidney processing of circulating hCG, but also points to possible multiple pathways of production of hCG cf in urine, as hCG cf was only 12·2% of the amount of hCG excreted in urine whereas, in pregnancy, hCG cf is present in much greater concentrations as compared with hCG (Norman et al 2000).…”

Section: Discussionmentioning

confidence: 77%

Metabolism of gonadotropins: comparisons of the primary structures of the human pituitary and urinary LH beta cores and the chimpanzee CG beta core demonstrate universality of core production

Birken

Gawinowicz²,

Maydelman³

et al. 2001

Journal of Endocrinology

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The gonadotropins are a family of closely related heterodimeric glycoprotein hormones homologous in structure to disulfide-knot growth factors. Metabolic proteolytic processing in vivo of this disulfide cross-linked region results in urinary excretion of a residual highly stable core structure. The primary structure of the pituitary form of the hLH core was reported earlier, but it has proved difficult to isolate the urinary core, although antibodies to the pituitary core demonstrated its presence. By conventional and immunoaffinity methods, the urinary core has been isolated and its structure determined by both chemical and mass spectrometric methods. The urinary hLH core is the same as the pituitary-extracted hLH core, 6-40 disulfide bridged to 55-93, except that the pituitary core is more heterogeneous containing also 49-93. These findings imply a dual origin of urinary cores, both directly from a secreting tissue and by kidney processing of circulating hormone. We also found that pregnant chimpanzees excrete a CG core with a primary structure identical to that of the human CG core of pregnancy. In conclusion, gonadotropin core generation and urinary excretion of nearly identical gonadotropin metabolites is common among primates. Although possible biological functions of these core fragments remain unproven, they have diagnostic utility because of their stability and abundance.

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“…A series of papers attest to the stability of this terminal metabolite of hCG which is excreted as a remarkably uniform molecule, composed of the hCGβ peptide chain structure of 6-40 disulfide-bridged to 55-92 (Birken et al, 1988;Birken et al, 1996). A series of metabolic studies including human studies by the groups of Nisula and that of Norman both presented data which indicated the hCGβcf was generated predominately by the kidney from hCG presumably absorbed and degraded within the renal tubule structures (de Medeiros et al, 1992a;de Medeiros et al, 1992b;Norman et al, 2000;Wehmann et al, 1984;Wehmann et al, 1989;Wehmann et al, 1990;Wehmann and Nisula, 1980). While authentic hCGβcf has only been isolated from urine and thus, is thought to be solely or mainly a kidney product derived from proteolytic digestion of hCG absorbed from the blood, hLHβcf has been purified both from pituitary tissue as well as from urine and the structures are the same.…”

Section: Discussionmentioning

confidence: 99%

Patterns of LHβcf among women in health and disease

Birken

McChesney

Yershova

et al. 2007

Molecular and Cellular Endocrinology

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Urine based gonadotropin assays provide a practical means of analyzing hormone secretion patterns. While research protocols have revealed pulsatile patterns of gonadotropins such as LH in the blood, these assays are of limited clinical use since daily venipuncture sampling is not feasible outside of a research environment. However, collection of several urine samples provides a method to achieve the same visualization of gonadotropin patterns in patients using a convenient and generally applicable technique based on analysis of the highly stable hLHβcf for monitoring LH and hCGβcf for monitoring pituitary hCG. We demonstrated that two different sampling techniques for analyzing these gonadotropin metabolites yielded the same information on their excretory patterns, either sampling of spot urines or collecting first morning void urines for several days. Next, we studied the core excretory patterns in several populations: menstruating and postmenopausal women from the general population, and two populations of women from a fertility center, one of which had polycystic ovaries (PCO). The PCO population was also subdivided into those with and without insulin resistance (IR). It was found that our hLHβcf assay did not measure the form of the LH core (vhLHβcf) produced in subjects who were homozygous for a variant form of LH (v-LH). None of our patients tested were homozygous for the variant form of LH. It was also found that in most non-PCO (NPCO) patients, the hLHβcf peak lasted for 7-9 days while among the PCO patients this peak frequently lasted for less than 7 days and an erratic pattern tended to appear. The overall differences in patterns between the PCO and NPCO patients were confirmed by spectral statistical methods. The prevalence of certain characteristic hLHβcf patterns may be higher among women with PCO with a more severe clinical presentation. Use of urinary analysis of gonadotropin metabolites, especially hLHβcf, may supplement subjective ultrasound studies with more sensitive biochemical measurements.

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hCGbeta core fragment is a metabolite of hCG: evidence from infusion of recombinant hCG

Cited by 25 publications

References 23 publications

Human chorionic gonadotropin (hCG) beta-core fragment is produced by degradation of hCG or free hCG beta in gestational trophoblastic tumors: a possible marker for early detection of persistent postmolar gestational trophoblastic disease

Human chorionic gonadotropin (hCG) beta-core fragment is produced by degradation of hCG or free hCG beta in gestational trophoblastic tumors: a possible marker for early detection of persistent postmolar gestational trophoblastic disease

Metabolism of gonadotropins: comparisons of the primary structures of the human pituitary and urinary LH beta cores and the chimpanzee CG beta core demonstrate universality of core production

Patterns of LHβcf among women in health and disease

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