Distribution of follitropin and deglycosylated follitropin in the rat: a quantitative and radioautographic study.
125I-labeled ovine follitropin (125I-oFSH) and deglycosylated follitropin (125I-DG-oFSH) were injected into rats and the tissue uptake was quantified and correlated with radioautographic data. Trichloroacetic acid (TCA)-precipitable radioactivity and gel filtration analysis of blood samples indicated no degradation of follitropin or analogue with time. Clearance of follitropin from the circulation was accelerated after its deglycosylation. Disappearance of both molecules from the blood was associated with uptake and/or loss of radioactivity from liver, kidney, ovary and spleen. The more rapid removal of deglycosylated follitropin from blood was associated with higher renal levels of accumulated radioactivity than native follitropin. This was associated with its localization within the cortex, specifically the proximal convoluted tubules of the nephron. Binding of 125I-labeled follitropin and analogue to granulosa cells was specific and time-dependent. 125-I-DG-oFSH demonstrated greater avidity of binding to rat granulosa cells with time than 125I-oFSH. This was associated with slower dissociation kinetics and/or metabolism for 125I-DG-oFSH. The absence of localization of either 125I-follitropin or analogue in hepatic tissue suggests that hepatic mechanisms may not significantly contribute to the clearance of these molecules. Implications of these findings in regard to the metabolism of oFSH and its antagonist are discussed.
D000818:Animals; D001345:Autoradiography; D001667:Binding, Competitive; D001693:Biological Transport, Active; D005260:Female; D005640:Follicle Stimulating Hormone / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D006107:Granulosa Cells / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution
C049669:follicle stimulating hormone, deglycosylated; D005640:Follicle Stimulating Hormone