Dissociation between tumor shrinkage and hormonal response during somatostatin analog treatment in an acromegalic patient: preferential expression of somatostatin receptor subtype 3.

INTRODUCTION: About a third of acromegalic patients is resistant to available SS analogs (SA), octreotide (OCT) and lanreotide (LAN). Such resistance is related to reduction of SS receptor (SSTR) density or to a different expression of SSTR subtypes. There are 5 known SSTR subtypes. SSTR2 and SSTR5 are usually expressed in GH-secreting pituitary tumors, and both SA bind preferentially to SSTR2 and, to a lesser extent, to SSTR5. We herein describe an acromegalic patient who presented impressive tumor shrinkage without hormonal normalization during primary therapy with SA. MATERIAL AND METHODS: This 23-yr-old male acromegalic patient was treated with slow-release LAN (LAN-SR), 30 mg every 10 days for six months, followed by OCT-LAR, 30 mg every 28 days for an additional six months with a 75% tumor volume reduction but without GH and IGF-I normalization. Subsequently, he underwent pituitary surgery and expression of SSTR in the removed tumor was performed by real time RT-PCR by the 2-deltaCt method, using GAPDH as internal control. All PCR products were confirmed by automated sequencing. RESULTS: SSTR expression revealed an unusual profile, with almost exclusively expression of SSTR3. CONCLUSIONS: These unusual clinical and receptor subtypes profile suggest an important role of SSTR3 on tumor shrinkage. The low affinity of LAN and OCT for this SSTR subtype could be compensated by its high expression in this GH-secreting pituitary macroadenoma.

Metallothionein isoform 3 gene is differentially expressed in corticotropin-producing pituitary adenomas.

In order to search for candidate genes related to pituitary adenoma aggressiveness, the present investigation was intended to compare the mRNA expression profile from a pool of four nonfunctional pituitary adenomas (NFPA) with a spinal cord metastasis of a nonfunctional pituitary carcinoma (MNFPC). The metallothionein isoform 3 (MT3) gene was differentially expressed in nonfunctional adenomas in comparison to the metastasis of nonfunctional carcinoma. A microarray dataset comprising 19,881 probes was employed for comparing expression profiles of a spinal cord metastasis of a nonfunctional pituitary carcinoma with a pool of four nonfunctional pituitary adenomas. RT-qPCR confirmed the microarray findings and was used to investigate MT3 mRNA gene expression in tumor samples of a series of 52 different pituitary adenoma subtypes comprising 10 corticotropin (ACTH)-producing, 18 growth hormone (GH)-producing, 8 prolactin (PRL)-producing, and 16 nonfunctional adenomas. Microarray data analysis by GeneSifter program unveiled Gene Ontology terms related to zinc ion-binding activity closely related to MT3 function. MT3 mRNA expression was statistically significantly higher in ACTH-producing pituitary adenomas and in nonfunctional pituitary adenomas in comparison to the other pituitary adenoma subtypes. The more abundant expression of this gene in ACTH-producing pituitary adenomas suggests that MT3 could be related to distinct pituitary cell lineage regulating the activity of some transcription factor of importance in hormone production and/or secretion.