Abstract
BackgroundSugar moieties of gonadotropins play no primary role in receptor binding but they strongly affect their circulatory half-life and consequently their in vivo biopotencies. In order to relate more precisely hepatic trapping of these glycoproteic hormones with their circulatory half-life, we undertook a comparative study of the distribution and elimination of porcine LH (pLH) and equine CG (eCG) which exhibit respectively a short and a long half-life. This was done first by following half-lives of pLH in piglets with hepatic portal circulation shunted or not. It was expected that such a shunt would enhance the short half-life of pLH. Subsequently, scintigraphic imaging of both 123I-pLH and 123I-eCG was performed in intact rats to compare their routes and rates of distribution and elimination.MethodsNative pLH or eCG was injected to normal piglets and pLH was tested in liver-shunted anæsthetized piglet. Blood samples were recovered sequentially over one hour time and the hormone concentrations were determined by a specific ELISA method. Scintigraphic imaging of 123I-pLH and 123I-eCG was performed in rats using a OPTI-CGR gamma camera.ResultsIn liver-shunted piglets, the half-life of pLH was found to be as short as in intact piglets (5 min). In the rat, the half-life of pLH was also found to be very short (3–6 min) and 123I-pLH was found to accumulate in high quantity in less than 10 min post injection at the level of kidneys but not in the liver. 123I-eCG didn't accumulate in any organ in the rats during the first hour, plasma concentrations of this gonadotropin being still elevated (80%) at this time.ConclusionIn both the porcine and rat species, the liver is not responsible for the rapid elimination of pLH from the circulation compared to eCG. Our scintigraphic experiments suggest that the very short circulatory half-life of LH is due to rapid renal trapping.
Highlights
Sugar moieties of gonadotropins play no primary role in receptor binding but they strongly affect their circulatory half-life and their in vivo biopotencies
Glycoprotein hormones (Luteinizing Hormone LH, Follicle-Stimulating Hormone FSH, Chorionic Gonadotropin CG and Thyroid-Stimulating Hormone TSH) are comprised of two dissimilar, non-covalently bound glycoproteic subunits, named α and β and their 1:1 association is mandatory for hormonal activity
These samples were centrifuged 10 minutes at 3000 g at 4°C and the hormones concentrations were determined in plasma by specific competition enzyme-linked immunosorbent assays (ELISA) for equine CG (eCG) [10] and porcine LH (pLH) [Lecompte F and Combarnous Y; unpublished]
Summary
Sugar moieties of gonadotropins play no primary role in receptor binding but they strongly affect their circulatory half-life and their in vivo biopotencies. In order to relate more precisely hepatic trapping of these glycoproteic hormones with their circulatory halflife, we undertook a comparative study of the distribution and elimination of porcine LH (pLH) and equine CG (eCG) which exhibit respectively a short and a long half-life. The α-subunit is common to all of them and it is encoded by an unique gene whereas the different β-subunits confer hormonal specificity to each αβ heterodimer It has been known for a long time that the sugar moieties of gonadotropins play no primary role in receptor binding affinity or specificity but that they strongly affect their circulatory half-life and their in vivo biopotencies. The terminal sialic acid residues of these hormones are important for their survival in circulation and desialylation which leads to a drop in their circulatory half-life results in an almost complete loss of in vivo bioactivity
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