Ross, Brian D.

AbstractMice homozygous for the targeted disruption of the glycoprotein hormone α-subunit (αGsu) display hypertrophy and hyperplasia of the anterior pituitary thyrotropes. Thyrotrope hyperplasia results in tumors in aged αGsu−/− 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 αGsu−/− mutants, we generated Smstr2−/−, αGsu−/− mice. Smstr2−/−, αGsu−/− mice develop hyperplasia of thyrotropes, similar to αGsu−/− mutants, demonstrating that SMSTR2 is dispensable for the development of pituitary adenomatous hyperplasia. Thyrotrope hyperplasia in Smstr2−/−, αGsu−/− mice regresses in response to T4 treatment, suggesting that SMSTR2 is not required in the T4 feedback loop regulating TSH secretion.

PurposeTo use 13C magnetic resonance spectroscopy (MRS) and 31P MRS to develop a direct assay for regional [HCO3−] in the human brain and to define brain pH and physiological response of [HCO3−] to fasting.Materials and MethodsSeven healthy subjects underwent MRS examinations on a 1.5T MRI scanner. Subjects were well fed with repeated examinations performed after 4 and 12 hours of fasting. Proton noise decoupling 13C MRS were acquired using pulse and acquired acquisition while 31P MRS were acquired using a 2D chemical shift imaging method with relaxation time (TR) of 2 seconds.ResultsFasting brain bicarbonate concentrations (6.7 ± 2.5 mM for 12‐hour fasting, P = 0.002 and 8.3 ± 2.1 mM for 4‐hour fasting, P = 0.015) are significantly reduced compared to fed state (11.6 ± 1.3 mM). However, no significant difference in brain pH was observed, confirming the critical role of pCO2 in intracerebral pH homeostasis.ConclusionWe demonstrated that the intracellular HCO3− in human brain is readily modified by diet but appears to have no measurable effect on cerebral pH. Natural abundance 13C can provide useful information relevant to human brain pH homeostasis by providing information for HCO3−. J. Magn. Reson. Imaging 2014;39:398–401. © 2013 Wiley Periodicals, Inc.