Differences in the metabolic clearance of pituitary and serum thyrotropin (TSH) derived from euthyroid and hypothyroid rats: effects of chemical deglycosylation of pituitary TSH.
We compared the MCR, volume of distribution, and rapid phase (rt1/2) and slow phase half-lives of purified pituitary rat (r) TSH, TSH from crude pituitary extracts of normal and hypothyroid rats, TSH from hypothyroid rat sera, and TSH secreted from hypothyroid rat pituitaries incubated in vitro. For 3 h after iv bolus injection into euthyroid rats, 125I-labeled rTSH was determined by acid precipitation in serum and various organs, and unlabeled TSH was measured by RIA. The MCR of TSH from normal pituitary extracts (0.53 +/- 0.02 ml/min) was similar to that of unlabeled purified rTSH (0.52 +/- 0.03), while those from hypothyroid pituitary extracts (0.32 +/- 0.03) and hypothyroid sera (0.33 +/- 0.01) were decreased. The reduced MCR of TSH from hypothyroid pituitaries was due to a decreased distribution volume (8.4 +/- 0.6 ml) compared to that from normal pituitaries (11.4 +/- 0.7) and hypothyroid sera (10.9 +/- 0.8). The decreased MCR of circulating TSH from hypothyroid sera reflected an increase in its rt1/2 (12.6 +/- 0.5 min) vs. that from both normal (5.1 +/- 0.5) and hypothyroid (5.7 +/- 0.4) pituitaries. The rt1/2 of secreted TSH from incubated hypothyroid rat pituitaries (8.5 +/- 0.9) was intermediate between those of circulating and pituitary forms of hypothyroid rTSH. The clearances of intact bovine TSH (bTSH) and deglycosylated bTSH (dg-bTSH) were compared. The dg-bTSH MCR was found to be increased (0.71 +/- 0.02 ml/min) compared to that of bTSH (0.59 +/- 0.02), primarily due to a decreased rt1/2 for dg-bTSH (3.8 +/- 0.1 min) vs. bTSH (4.7 +/- 0.2). Uptake of purified [125I]rTSH was highest in the kidney at all times, varying from 43% of the injected dose at 5 min to 54% at 180 min. We conclude that in the euthyroid rat, 1) the metabolic clearance of TSH differs between pituitary and serum forms and appears to depend on specific molecular features that vary with the physiological state of the animal from which the TSH is derived; 2) since chemical deglycosylation increased the clearance of TSH, we speculate that the chemical basis for changes in TSH clearance may be related to alterations in its carbohydrate structure; and 3) for normal pituitary TSH, the kidney is the major organ of clearance.
D000818:Animals; D006023:Glycoproteins / Q000378:metabolism; D007037:Hypothyroidism / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate; D010902:Pituitary Gland / Q000378:metabolism*; D051381:Rats; D013329:Structure-Activity Relationship; D013961:Thyroid Gland / Q000378:metabolism; D013972:Thyrotropin / Q000097:blood / Q000378:metabolism*; D014018:Tissue Distribution
D006023:Glycoproteins; D013972:Thyrotropin