Effect of diabetes mellitus on thyrotropin release from isolated rat thyrotrophs.
The effect of streptozotocin-induced diabetes on thyrotropin (TSH) secretion was studied in vitro in male rats, using purified thyrotrophs isolated by centrifugal elutriation. The development of diabetes was associated with a significant fall in serum T4 (4.9 +/- 1.5 vs. 1.2 +/- 0.7 micrograms/dl, control vs. diabetic), T3 (59 +/- 16 vs. 20 +/- 9 ng/dl) and TSH (53 +/- 22 vs. 23 +/- 18 microU/ml). In vitro, basal TSH release was lower in cells from diabetic rats (1570 +/- 248 microU/10(6) cells) than in controls (2612 +/- 765 microU/10(6) cells) after 48 h in culture. Furthermore, thyrotropin-releasing hormone (TRH)-induced TSH release was decreased about 30% and the intracellular TSH content was also reduced 45% in diabetic rat thyrotrophs compared with controls. The addition of 200 microU/ml of insulin in the incubation media did not change the TRH-stimulated TSH release, but it decreased the basal TSH release by 42%. Preincubation of thyrotrophs with glucose (25 mM) did not impair the basal or TRH-stimulated TSH release. In the same experimental conditions, no effect of insulin or glucose was seen on the basal or TRH-stimulated TSH release from thyrotrophs of diabetic rats. Preincubation of thyrotrophs with 10, 100, or 1000 nM of T4 for 48 h decreased basal TSH release by 27%, 45%, and 48%, respectively, and reduced TRH-induced TSH release by 46%, 48%, and 55%; 100 nM T4 also reduced TRH-induced TSH release from diabetic thyrotrophs.(ABSTRACT TRUNCATED AT 250 WORDS)
Endocrinology Research Laboratory, Wadsworth Veterans Administration Medical Center, Los Angeles, California 90073.
H
H
Chamras
J M
JM
Hershman
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013972:Thyrotropin / Q000378:metabolism*; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology; D013974:Thyroxine / Q000494:pharmacology
D013973:Thyrotropin-Releasing Hormone; D013972:Thyrotropin; D013974:Thyroxine; D015056:1-Methyl-3-isobutylxanthine