Cortistatin inhibits growth hormone release from human fetal and adenoma pituitary cells and prolactin secretion from cultured prolactinomas.
BACKGROUND
Cortistatin (CST) is a neuropeptide that shares high homology with somatostatin and binds with high affinity to all somatostatin receptor (SSTR) subtypes. Many of its endocrine and biological activities overlap with those of somatostatin.


OBJECTIVE
The objective of the study was to assess the direct in vitro effects of CST on human pituitary hormone secretion.


METHODS
This study was performed in the endocrine laboratory of a tertiary academic medical center.


METHODS
Primary cell cultures of human fetal (21-25 wk gestation) pituitary tissues and cultured hormone-secreting adenoma cells were used in this study.


METHODS
Cell cultures were incubated with CST-14 or CST-17, somatostatin, GHRH, SSTR analogs, and ghrelin analogs, and hormone secretion was analyzed.


METHODS
GH and prolactin (PRL) medium concentrations were tested by hormone assay, and SSTR mRNA was tested by RT-PCR.


RESULTS
CST-14 (10 nm) inhibited GH secretion by up to 65% in all fetal pituitary specimens after 4-h incubation (P < 0.05). CST-14 or CST-17 (10 nm) inhibited basal GH secretion in six of the 13 GH-cell adenomas and two of the three GH-PRL mixed adenomas. CST-17 (100 nm) suppressed the GH response to GHRH and ghrelin analog (10 nm each) by 30-50% in adenomas (P < 0.05). Three PRL-adenomas treated with CST-17 (10 nm) showed a 20-40% inhibition of PRL release (P < 0.05), whereas in three others no suppression or mild response was achieved at this concentration. A comparable inhibition of PRL secretion was obtained with SSTR5-selective analog but significantly less with SSTR2-preferential compounds. RT-PCR revealed the expression of both SSTR2 and SSTR5 in all GH-cell and mixed adenomas studied and all PRL-secreting adenomas studied, except for two of the CST-resistant prolactinomas, in which SSTR5 was absent.


CONCLUSIONS
This is the first report of in vitro CST suppression of human GH and PRL in cultured pituitary tissues. The regulation of PRL release from cultured adenomas appears to be primarily mediated by SSTR5.
Rubinfeld
Hadara
H
Institute of Endocrinology and Metabolism, Rabin Medical Center, Beilinson Campus, Petach Tikva 49100, Israel.
Hadani
Moshe
M
Barkai
Gad
G
Taylor
John E
JE
Culler
Michael D
MD
Shimon
Ilan
I
D000236:Adenoma / Q000378:metabolism*; D005333:Fetus / Q000378:metabolism*; D019382:Human Growth Hormone / Q000378:metabolism*; D006801:Humans; D009479:Neuropeptides / Q000494:pharmacology*; D010902:Pituitary Gland / Q000187:drug effects* / Q000378:metabolism; D010911:Pituitary Neoplasms / Q000378:metabolism*; D011388:Prolactin / Q000378:metabolism*; D015175:Prolactinoma / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D009479:Neuropeptides; C099323:cortistatin; D019382:Human Growth Hormone; D011388:Prolactin