ABSTRACT
The origins of a fragment of the human chorionic gonadotrophin (hCG) molecule, β-core (βC-hCG) were studied by analysis of βC-hCG concentrations in biological fluids. In addition, the ability of the placenta to produce the fragment and the metabolism of hCG to βC-hCG by human granulosa cells was determined in tissue culture. Finally the conversion of exogenous hCG to βC-hCG was studied in vivo. The fragment was present in pregnancy urine as well as that from premenopausal and postmenopausal subjects.
The highest concentrations were found in pregnant women. Ratios of βC-hCG to intact hCG were higher in pregnancy urine when radioimmunoassay (RIA) was used compared with immunoradiometric assay (IRMA) (0·67 and 0·37 respectively). Concentrations of βC-hCG were higher in postmenopausal urine than in premenopausal specimens.
A significant amount of a high molecular weight βC-hCG immunoreactive material was found in serum samples after size separation, and the molar ratio of βC-hCG/hCG was estimated as 0·019. Amniotic fluid also contained small quantities of two forms of immunoreactive βC-hCG and the ratio of 0·01 for authentic βC-hCG/hCG increased to 0·026 when the high molecular weight form was considered. Cultured trophoblastic tissue released material with βC-hCG immunoreactivity in the medium and chromatographic separation revealed that the majority of this material was of higher molecular weight compared with the authentic βC-hCG form. βC-hCG was the principal glycoprotein found in follicular fluid after hyperstimulated folliculogenesis and intramuscular injection of 5000 IU hCG. We also demonstrated that 26% of follicular fluid samples (n = 50) were positive for βC-hCG; levels ranged from 5·2 to 23·0 pmol/l (13·1 ±5·7); s.d.) when a specific IRMA was used. The RIA could detect βC-hCG in 48 samples (96%), levels ranging from 7·0 to 28·5 pmol/l (19·4±5·2). Moreover, granulosa cells cultured in the presence of hCG were able to degrade the intact molecule to both high molecular weight and authentic immunoreactive forms of βC-hCG. After gel filtration, material of molecular weight over a wide range and immunoreactive for βC-hCG was present in human seminal plasma. Assaying 74 samples of this fluid by IRMA, βC-hCG was detected in 42 (56·7%), levels ranging between 5·5 and 59·5 pmol/l (24·9± 15·2).
Following intramuscular injection of 1500 IU hCG into male volunteers, the levels of βC-hCG in urine increased by approximately 220% during the first 24 h (P= 0·036 for βC-hCG levels at 2 h and 24 h), decreasing thereafter to undetectable levels in the next 72 h. However, in serum, βC-hCG immunoactivity remained under the limit of detection of the assay at all times. We concluded that (1) the βC-hCG fragment is widely distributed in body fluids and a dissociable high molecular weight material immunoreactive for βC-hCG is found in some biological compartments; (2) granulosa-lutein cells are able to degrade intact hCG to a small βC-hCG immunoreactive fragment; (3) trophoblastic cells synthesize and release different size material with βC-hCG immunoreactivity; (4) intramuscular injection of hCG is followed by increased βC-hCG immunoreactivity in urine; and (5) our results support previous studies indicating the peripheral metabolism of intact hCG to βC-hCG as the principal source for this fragment but raise the possibility that a high molecular weight-associated form, probably bound to a specific protein, may be produced by some tissues.
Journal of Endocrinology (1992) 135, 175–188
Human chorionic gonadotrophin-induced hyperemesis and hyperthyroidism in pregnancy