Fast renal trapping of porcine luteinizing hormone (pLH) shown by 123I-scintigraphic imaging in rats explains its short circulatory half-life.
BACKGROUND
Sugar 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.


METHODS
Native pLH or eCG was injected to normal piglets and pLH was tested in liver-shunted anaesthetized 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.


RESULTS
In 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.


CONCLUSIONS
In 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.
Klett
Danièle
D
INRA-CNRS UMR 6073 Physiologie de la Reproduction et des Comportements, 37380 Nouzilly, France. Daniele.Klett@tours.inra.fr
Bernard
Serge
S
Lecompte
François
F
Leroux
Hervé
H
Magallon
Thierry
T
Locatelli
Alain
A
Lepape
Alain
A
Combarnous
Yves
Y
D000818:Animals; D006063:Chorionic Gonadotropin / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D005260:Female; D006031:Glycosylation; D006207:Half-Life; D006736:Horses; D007275:Injections, Intravenous; D007457:Iodine Radioisotopes / Q000032:analysis / Q000493:pharmacokinetics*; D007668:Kidney / Q000000981:diagnostic imaging / Q000378:metabolism*; D008099:Liver / Q000000981:diagnostic imaging / Q000378:metabolism; D007986:Luteinizing Hormone / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D019158:N-Acetylneuraminic Acid / Q000737:chemistry; D011168:Portal System / Q000502:physiology; D011170:Portasystemic Shunt, Surgical; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000032:analysis / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D013045:Species Specificity; D013552:Swine; D014018:Tissue Distribution
D006063:Chorionic Gonadotropin; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D007986:Luteinizing Hormone; D019158:N-Acetylneuraminic Acid