Hiroyuki Murabe

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.

Role of adrenomedullin and its receptor system in renal pathophysiology

Adrenomedullin (AM), a potent vasorelaxing, natriuretic and cell growth-modulating peptide, is thought to act as an autocrine/paracrine regulator in renal glomeruli and tubules. AM receptors comprise the calcitonin receptor-like receptor (CRLR) and a family of receptor-activity-modifying proteins (RAMPs 1-3); however, the pathophysiological role of AM and its receptor system in the kidney remains to be clarified. We examined the regulation of their expression in a rat model of renal injury and found that RAMP1, RAMP2 and CRLR expressions were markedly upregulated upon induction of fibrosis during obstructive nephropathy. Since AM exerts potent antiproliferative effects in various cell types, upregulation of the AM receptor system may play important roles in modulating the progression of renal diseases.

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.

Growth hormone-secreting pituitary adenoma associated with multiple bone cysts, skin pigmentation and aortitis syndrome

McCune-Albright syndrome (MAS) is clinically characterized by polyostotic fibrous dysplasia, cafe au lait pigmentation of the skin and multiple endocrinopathies. Recently activating mutations of codon 201 in the gene encoding Gs alpha have been found in affected tissues in MAS. Herein we report a case of acromegaly associated with multiple bone cysts and skin pigmentation in a 47-year-old woman. She had suffered a history of aortitis syndrome. The DNA sequence indicated that a Cys201 for Arg201 substitution was found in the GH secreting pituitary adenoma tissue but not in peripheral mononuclear cells. We speculate that the patient has a possible variant form of MAS characterized by multiple bone lesions skin pigmentation and GH-secreting pituitary adenoma.

Hypercalcemic crisis resulting from near drowning in an indoor public bath

Patient: Male, 66 Final Diagnosis: Hypercalcemic crisis Symptoms: Near drowning state Medication: — Clinical Procedure: — Specialty: Critical care medicine Objective: Challenging differential diagnosis Background: Hypercalcemic crisis, generally caused by malignancy or primary hyperparathyroidism, is a life-threatening emergency that can result in multi-organ failure. Lowering the patient’s calcium level immediately and determining the correct etiology are essential. Case Report: We report a case of hypercalcemic crisis with a novel etiology. A 66-year-old male presented to the emergency room in cardiac arrest with a ventricular arrhythmia after being discovered submerged in an indoor public bath. He underwent cardioversion and was emergently intubated. Computed tomography showed bilateral pulmonary edema, suspected from water aspiration. Laboratory data revealed severe hypercalcemia and mild hypernatremia. Following three days of continuous hemodiafiltration, serum Ca decreased to and remained within normal limits. We concluded the etiology of hypercalcemia was absorption of Ca resulting from aspirated water. Conclusions: Near drowning can be a cause of hypercalcemic crisis. For cases of near drowning, it is important to investigate the source of the aspirated water and consider electrolyte abnormalities in the diagnosis.