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

Klett D, Bernard S, Lecompte F, Leroux H, Magallon T, Locatelli A, Lepape A, Combarnous Y - Reprod. Biol. Endocrinol. (2003)

Bottom Line: In liver-shunted piglets, the half-life of pLH was found to be as short as in intact piglets (5 min).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.

View Article: PubMed Central - HTML - PubMed

Affiliation: INRA-CNRS UMR 6073 Physiologie de la Reproduction et des Comportements, 37380 Nouzilly, France. Daniele.Klett@tours.inra.fr

ABSTRACT

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.

Conclusion: 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.

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Half-life of 123I-pLH and 123I-eCG in rats by scintigraphy. Quantitation of emission at the level of heart was used to follow residual concentrations of radioiodinated hormones in blood. Half-life of 123I-pLH was determined by non-linear regression of relative intensities as a function of time.
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Figure 4: Half-life of 123I-pLH and 123I-eCG in rats by scintigraphy. Quantitation of emission at the level of heart was used to follow residual concentrations of radioiodinated hormones in blood. Half-life of 123I-pLH was determined by non-linear regression of relative intensities as a function of time.

Mentions: Immediatly after IV injection, radiolabeled pLH was seen in highly vascularized organs, such as heart, lungs and liver (figure 3; left panel). They exhibited a rapid clearance in these organs and we determined the t1/2 of 123I-pLH by following its emission in blood at heart level making the assumption that there is no binding of LH in heart (figure 4). A t1/2 value of 2.64 min (95%CL 2.26–3.18) for 123I-pLH was calculated. Accumulation of radioiodinated pLH occurred in the kidneys: 14% of the total injected dose was recovered in the left kidney only ten minutes after injection. When whole body scintigraphic images were examined (figure 3), it appeared that all radioactivity was localized in the renal tract in less than 10 minutes p.i., with very low activity observed in urinary bladder. In the liver, radioactivity appeared fugaciously, and disappeared very rapidly. No radioactivity was present in stomach and intestine until 30 minutes p.i., and thyroid became visible only after 60 minutes p.i. At this time, the different activities observed for the left and the right kidneys could be ascribed to stomach superimposition over kidney. No significant accumulation of radioactivity in genitals nor in any other extravascular compartment was observed.


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

Klett D, Bernard S, Lecompte F, Leroux H, Magallon T, Locatelli A, Lepape A, Combarnous Y - Reprod. Biol. Endocrinol. (2003)

Half-life of 123I-pLH and 123I-eCG in rats by scintigraphy. Quantitation of emission at the level of heart was used to follow residual concentrations of radioiodinated hormones in blood. Half-life of 123I-pLH was determined by non-linear regression of relative intensities as a function of time.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC239891&req=5

Figure 4: Half-life of 123I-pLH and 123I-eCG in rats by scintigraphy. Quantitation of emission at the level of heart was used to follow residual concentrations of radioiodinated hormones in blood. Half-life of 123I-pLH was determined by non-linear regression of relative intensities as a function of time.
Mentions: Immediatly after IV injection, radiolabeled pLH was seen in highly vascularized organs, such as heart, lungs and liver (figure 3; left panel). They exhibited a rapid clearance in these organs and we determined the t1/2 of 123I-pLH by following its emission in blood at heart level making the assumption that there is no binding of LH in heart (figure 4). A t1/2 value of 2.64 min (95%CL 2.26–3.18) for 123I-pLH was calculated. Accumulation of radioiodinated pLH occurred in the kidneys: 14% of the total injected dose was recovered in the left kidney only ten minutes after injection. When whole body scintigraphic images were examined (figure 3), it appeared that all radioactivity was localized in the renal tract in less than 10 minutes p.i., with very low activity observed in urinary bladder. In the liver, radioactivity appeared fugaciously, and disappeared very rapidly. No radioactivity was present in stomach and intestine until 30 minutes p.i., and thyroid became visible only after 60 minutes p.i. At this time, the different activities observed for the left and the right kidneys could be ascribed to stomach superimposition over kidney. No significant accumulation of radioactivity in genitals nor in any other extravascular compartment was observed.

Bottom Line: In liver-shunted piglets, the half-life of pLH was found to be as short as in intact piglets (5 min).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.

View Article: PubMed Central - HTML - PubMed

Affiliation: INRA-CNRS UMR 6073 Physiologie de la Reproduction et des Comportements, 37380 Nouzilly, France. Daniele.Klett@tours.inra.fr

ABSTRACT

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.

Conclusion: 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.

Show MeSH
Related in: MedlinePlus