INTRODUCTION: It has been reported in some series that gsp+ somatotropinomas are more sensitive to somatostatin analogues (SA) and dopamine's actions which may be related to their somatostatin receptor (SSTR) and dopamine receptor (DR) profile. No previous studies have been undertaken to evaluate the SSTR and DR profile related with the gsp status in somatotropinomas. OBJECTIVES: To determine if (1) gsp status is correlated with response to octreotide LAR (LAR) and tumor expression patterns of SSTR1-5 and DR1-5 and (2) cAMP level can directly modulate SSTR and DR mRNA levels. METHODS: Response to SA was evaluated by GH and IGF-I percent reduction after 3 and 6 months of treatment with LAR. Conventional PCR and sequencing were used to identify gsp+ tumors. Quantitative real-time PCR was used to determine SSTR and DR tumor expression. Primary pituitary cell cultures of primates were used to study whether SSTR and DR expression is regulated by forskolin. RESULTS: The response to LAR did not significantly differ between patients with gsp+ and gsp- tumors; however, gsp+ tumors expressed higher levels of SSTR1, SSTR2, DR2 and a lower level of SSTR3. Forskolin increased SSTR1, SSTR2, DR1 and DR2 expression in cell cultures. CONCLUSION: Elevated SSTR1, SSTR2, and DR2 tumor expression may help improve responsiveness to SA and DA therapy; however, this study may not have been appropriately powered to observe significant effects in the clinical response. Elevated cAMP levels could be directly responsible for the upregulation in SSTR1, SSTR2 and DR2 mRNA levels observed in gsp+ patients.
INTRODUCTION: It has been reported in some series that gsp+ somatotropinomas are more sensitive to somatostatin analogues (SA) and dopamine's actions which may be related to their somatostatin receptor (SSTR) and dopamine receptor (DR) profile. No previous studies have been undertaken to evaluate the SSTR and DR profile related with the gsp status in somatotropinomas. OBJECTIVES: To determine if (1) gsp status is correlated with response to octreotide LAR (LAR) and tumor expression patterns of SSTR1-5 and DR1-5 and (2) cAMP level can directly modulate SSTR and DR mRNA levels. METHODS: Response to SA was evaluated by GH and IGF-I percent reduction after 3 and 6 months of treatment with LAR. Conventional PCR and sequencing were used to identify gsp+ tumors. Quantitative real-time PCR was used to determine SSTR and DR tumor expression. Primary pituitary cell cultures of primates were used to study whether SSTR and DR expression is regulated by forskolin. RESULTS: The response to LAR did not significantly differ between patients with gsp+ and gsp- tumors; however, gsp+ tumors expressed higher levels of SSTR1, SSTR2, DR2 and a lower level of SSTR3. Forskolin increased SSTR1, SSTR2, DR1 and DR2 expression in cell cultures. CONCLUSION: Elevated SSTR1, SSTR2, and DR2 tumor expression may help improve responsiveness to SA and DA therapy; however, this study may not have been appropriately powered to observe significant effects in the clinical response. Elevated cAMP levels could be directly responsible for the upregulation in SSTR1, SSTR2 and DR2 mRNA levels observed in gsp+ patients.
Authors: Raúl M Luque; Alejandro Ibáñez-Costa; Leonardo Vieira Neto; Giselle F Taboada; Daniel Hormaechea-Agulla; Leandro Kasuki; Eva Venegas-Moreno; Alberto Moreno-Carazo; María Ángeles Gálvez; Alfonso Soto-Moreno; Rhonda D Kineman; Michael D Culler; Manuel D Gahete; Mônica R Gadelha; Justo P Castaño Journal: Cancer Lett Date: 2015-01-28 Impact factor: 8.679
Authors: L E A Wildemberg; L V Neto; D F Costa; L E Nasciuti; C M Takiya; L M Alves; A Rebora; F Minuto; D Ferone; M R Gadelha Journal: J Endocrinol Invest Date: 2012-03-26 Impact factor: 4.256
Authors: Zhi Rong Qian; Tingting Li; Monica Ter-Minassian; Juhong Yang; Jennifer A Chan; Lauren K Brais; Yohei Masugi; Arunthathi Thiaglingam; Nichole Brooks; Reiko Nishihara; Mireille Bonnemarie; Atsuhiro Masuda; Kentaro Inamura; Sun A Kim; Kosuke Mima; Yasutaka Sukawa; Ruoxu Dou; Xihong Lin; David C Christiani; Fabien Schmidlin; Charles S Fuchs; Umar Mahmood; Shuji Ogino; Matthew H Kulke Journal: Pancreas Date: 2016-11 Impact factor: 3.327