Abstract
Extracellular Ca2+-sensing receptor (CaSR) has been recently identified in rat and mouse pituitary and in AtT-20 cells. The aim of the study was to investigate the presence of CaSR in the human pituitary and its signaling pathway. Normal parathyroid biopsies, autoptic normal pituitaries, and seven nonfunctioning and six GH-secreting adenomas were studied. Southern blot analysis of the RT-PCR products from pituitary adenomas indicated that the PCR fragments obtained were products of specific amplification of CaSR messenger ribonucleic acid. Sequence analysis showed nucleotide identity of these products with the available human parathyroid CaSR. By immunoblotting analysis CaSR, was detected in normal and adenomatous pituitary tissues. In all tumors studied, extracellular Ca2+ (2.5 mmol/L) induced a significant increase in intracellular Ca2+, mainly due to Ca2+ mobilization (from 82.7 ± 11 to 148 ± 36 nmol/L; P <0.001). Similar results were obtained with the CaSR activators gadolinium and neomycin. Moreover, CaSR activators significantly increased cAMP levels; this effect was not mimicked by other agents able to increase intracellular Ca2+, such as TRH. CaSR agonists did not increase resting GH secretion in any GH-secreting adenomas, but amplified the GH response to GHRH. In this study we first demonstrate CaSR expression in the human pituitary and provides evidence for an additional mechanism by which calcium might regulate pituitary cell function.
| Original language | English |
|---|---|
| Pages (from-to) | 2848-2853 |
| Number of pages | 6 |
| Journal | Journal of Clinical Endocrinology and Metabolism |
| Volume | 84 |
| Issue number | 8 |
| Publication status | Published - 1999 |
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ASJC Scopus subject areas
- Biochemistry
- Endocrinology, Diabetes and Metabolism
Cite this
Expression of calcium-sensing receptor and characterization of intracellular signaling in human pituitary adenomas. / Romoli, Roberto; Lania, Andrea; Mantovani, Giovanna; Corbetta, Sabrina; Persani, Luca; Spada, Anna.
In: Journal of Clinical Endocrinology and Metabolism, Vol. 84, No. 8, 1999, p. 2848-2853.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Expression of calcium-sensing receptor and characterization of intracellular signaling in human pituitary adenomas
AU - Romoli, Roberto
AU - Lania, Andrea
AU - Mantovani, Giovanna
AU - Corbetta, Sabrina
AU - Persani, Luca
AU - Spada, Anna
PY - 1999
Y1 - 1999
N2 - Extracellular Ca2+-sensing receptor (CaSR) has been recently identified in rat and mouse pituitary and in AtT-20 cells. The aim of the study was to investigate the presence of CaSR in the human pituitary and its signaling pathway. Normal parathyroid biopsies, autoptic normal pituitaries, and seven nonfunctioning and six GH-secreting adenomas were studied. Southern blot analysis of the RT-PCR products from pituitary adenomas indicated that the PCR fragments obtained were products of specific amplification of CaSR messenger ribonucleic acid. Sequence analysis showed nucleotide identity of these products with the available human parathyroid CaSR. By immunoblotting analysis CaSR, was detected in normal and adenomatous pituitary tissues. In all tumors studied, extracellular Ca2+ (2.5 mmol/L) induced a significant increase in intracellular Ca2+, mainly due to Ca2+ mobilization (from 82.7 ± 11 to 148 ± 36 nmol/L; P <0.001). Similar results were obtained with the CaSR activators gadolinium and neomycin. Moreover, CaSR activators significantly increased cAMP levels; this effect was not mimicked by other agents able to increase intracellular Ca2+, such as TRH. CaSR agonists did not increase resting GH secretion in any GH-secreting adenomas, but amplified the GH response to GHRH. In this study we first demonstrate CaSR expression in the human pituitary and provides evidence for an additional mechanism by which calcium might regulate pituitary cell function.
AB - Extracellular Ca2+-sensing receptor (CaSR) has been recently identified in rat and mouse pituitary and in AtT-20 cells. The aim of the study was to investigate the presence of CaSR in the human pituitary and its signaling pathway. Normal parathyroid biopsies, autoptic normal pituitaries, and seven nonfunctioning and six GH-secreting adenomas were studied. Southern blot analysis of the RT-PCR products from pituitary adenomas indicated that the PCR fragments obtained were products of specific amplification of CaSR messenger ribonucleic acid. Sequence analysis showed nucleotide identity of these products with the available human parathyroid CaSR. By immunoblotting analysis CaSR, was detected in normal and adenomatous pituitary tissues. In all tumors studied, extracellular Ca2+ (2.5 mmol/L) induced a significant increase in intracellular Ca2+, mainly due to Ca2+ mobilization (from 82.7 ± 11 to 148 ± 36 nmol/L; P <0.001). Similar results were obtained with the CaSR activators gadolinium and neomycin. Moreover, CaSR activators significantly increased cAMP levels; this effect was not mimicked by other agents able to increase intracellular Ca2+, such as TRH. CaSR agonists did not increase resting GH secretion in any GH-secreting adenomas, but amplified the GH response to GHRH. In this study we first demonstrate CaSR expression in the human pituitary and provides evidence for an additional mechanism by which calcium might regulate pituitary cell function.
UR - http://www.scopus.com/inward/record.url?scp=0033326948&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033326948&partnerID=8YFLogxK
M3 - Article
C2 - 10443690
AN - SCOPUS:0033326948
VL - 84
SP - 2848
EP - 2853
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 8
ER -