Thyroid hormone-responsive pituitary hyperplasia independent of somatostatin receptor 2.
Mice homozygous for the targeted disruption of the glycoprotein hormone alpha-subunit (alphaGsu) display hypertrophy and hyperplasia of the anterior pituitary thyrotropes. Thyrotrope hyperplasia results in tumors in aged alphaGsu(-/-) mice. These adenomatous pituitaries can grow independently as intrascapular transplants in hypothyroid mice, suggesting that they have progressed beyond simple hyperplasia. We used magnetic resonance imaging to follow the growth and regression of thyrotrope adenomatous hyperplasia in response to thyroid hormone treatment and discovered that the tumors retain thyroid hormone responsiveness. Somatostatin (SMST) and its diverse receptors have been implicated in cell proliferation and tumorigenesis. To test the involvement of SMST receptor 2 (SMSTR2) in pituitary tumor progression and thyroid hormone responsiveness in alphaGsu(-/-) mutants, we generated Smstr2(-/-), alphaGsu(-/-) mice. Smstr2(-/-), alphaGsu(-/-) mice develop hyperplasia of thyrotropes, similar to alphaGsu(-/-) mutants, demonstrating that SMSTR2 is dispensable for the development of pituitary adenomatous hyperplasia. Thyrotrope hyperplasia in Smstr2(-/-), alphaGsu(-/-) mice regresses in response to T4 treatment, suggesting that SMSTR2 is not required in the T4 feedback loop regulating TSH secretion.
Brinkmeier
M L
ML
Department of Human Genetics, University of Michigan, Ann Arbor, Michigan 48109-0638, USA.
Stahl
J H
JH
Gordon
D F
DF
Ross
B D
BD
Sarapura
V D
VD
Dowding
J M
JM
Kendall
S K
SK
Lloyd
R V
RV
Ridgway
E C
EC
Camper
S A
SA
D000818:Animals; D015152:Blotting, Northern; D005260:Female; D015292:Glycoprotein Hormones, alpha Subunit / Q000235:genetics / Q000502:physiology; D006965:Hyperplasia / Q000473:pathology; D007037:Hypothyroidism / Q000473:pathology; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010911:Pituitary Neoplasms / Q000235:genetics / Q000473:pathology*; D012313:RNA / Q000737:chemistry / Q000302:isolation & purification; D017481:Receptors, Somatostatin / Q000235:genetics / Q000502:physiology*; D013974:Thyroxine / Q000494:pharmacology*
D015292:Glycoprotein Hormones, alpha Subunit; D017481:Receptors, Somatostatin; D012313:RNA; C093733:somatostatin receptor 2; D013974:Thyroxine