Haruo Mizuta

Expression of Somatostatin Receptor (SSTR) Subtypes in Pituitary Adenomas: Quantitative Analysis of SSTR2 mRNA by Reverse Transcription-Polymerase Chain Reaction

The expression of somatostatin receptor (SSTR) subtypes and relative abundance of SSTR2 mRNA were examined in 18 pituitary adenomas using the reverse transcription‐polymerase chain reaction (RT‐PCR) method. SSTR1 and SSTR2 were expressed in all pituitary adenomas examined. Six of 9 somatotroph adenomas, 1 of 4 lactotroph adenomas and 1 of 2 thyrotroph adenomas also expressed SSTR5. SSTR3 and SSTR4 mRNAs were detected in 1 and 2 cases of somatotroph adenoma, respectively. SSTR2 mRNA expression was quantified by comparison with the PCR cycle‐dependent amplification of β‐actin or cyclophilin. The relative abundance of SSTR2 mRNA varied greatly among adenomas with more than a 1000‐fold difference. SSTR2 mRNAs in lactotroph adenomas were less abundant (P<0.01) than those in somatotroph adenomas. No significant correlation was found between the relative abundance of SSTR2 mRNA levels and GH sensitivity to octreotide administration. However, one of the thyrotroph adenomas exhibited marked shrinkage in tumor size after octreotide therapy, in which SSTR2 mRNA was the most abundant among the adenomas examined. GH sensitivity to octreotide was not significantly different between SSTR5 mRNA positive and negative adenomas. In conclusion, SSTR2 mRNA levels varied greatly among pituitary adenomas but were not correlated with GH sensitivity to octreotide. Further investigations of functional SSTR subtype proteins and of postreceptor signal transductions are required to clarify the molecular mechanisms of octreotide action.

Decreased neurotrophin-3 expression in skeletal muscles of streptozotocin-induced diabetic rats

The expression of neurotrophin-3 (NT-3) in skeletal muscles was measured in rats with streptozotocin (STZ)-induced diabetes using Northern blot analysis. At 6 weeks after STZ induction of diabetes, the NT-3 mRNA level in the quadriceps and gastrocnemius muscles was decreased by 45 and 77%, respectively, compared with that in age-matched controls. Since NT-3 is considered to be essential for the maintenance of spinal proprioceptive afferent neurons, decreased NT-3 expression in target tissues would impair the integrity of afferent neurons and might be an earlier marker in the sensory neuronal damage observed in diabetes mellitus.

Calcitonin gene-related peptide as a GH secretagogue in human and rat pituitary somatotrophs

To elucidate the role of calcitonin gene-related peptide (CGRP) in regulating pituitary function, we investigated the effects of CGRP and the related peptide adrenomedullin (AdM) on the secretion of growth hormone (GH) in vitro from human pituitary adenoma cells, rat pituitary tumor (GH3) cells, and normal rat pituitary cells. In 3 of 5 human somatotroph adenomas, GH secretion was stimulated by CGRP (1-100 nM). In one case of somatotroph adenoma, GH release was observed following the addition of 10 nM GHRH and 10 nM CGRP. The addition of CGRP or AdM (1 pM-10 nM) evoked GH secretion from GH3 cells with a bell-shaped distribution curve. CGRP (100 pM) caused the maximum increase of GH secretion (172+/-14 (mean+/-S.D.)% of control). The addition of CGRP8-37, an antagonist of CGRP type 1 receptors, inhibited the stimulatory effect of AdM but did not inhibit the effect of CGRP. The addition of CGRP and AdM evoked moderate GH secretion from normal rat pituitary cells. These results suggested that CGRP is a new GH secretagogue in human and rat pituitary tumor cells.

Late-onset familial amyloid polyneuropathy: an autopsy study of two Japanese brothers.

We report an autopsy study of late-onset familial amyloid polyneuropathy with a variant transthyretin Val30Met in 2 brothers living in Kyoto, Japan. The disease onsets were at 64 and 59 years, and they died at 71 and 74 years old, respectively. They exhibited almost the same postmortem Jindings. Amyloid deposition was remarkable in the hearts, but was not seen in the renal glomeruli. In the peripheral nervous system, amyloid deposition was most prominent in the nerves immediately caudal to ganglia, moderate in the dorsal and sympathetic ganglia, and mild in the spinal roots, sciatic nerves, and distal nerves. The difference between the amyloid deposition in the proximal portion and distal portion of the extremity nerves appeared to be greater in the late-onset type than in the ordinary type, and this proximal deposition of amyloid may have induced severe distal nerve Pber degeneration.