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This version published online on July 26, 2007
Endocrinology, doi:10.1210/en.2007-0378
A more recent version of this article appeared on December 1, 2007
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Submitted on March 21, 2007
Accepted on July 16, 2007

Regulation of growth hormone and prolactin gene expression and secretion by chimeric somatostatin-dopamine molecules

Anna Gruszka, Song-Guang Ren, Jesse Dong, Michael D. Culler, and Shlomo Melmed*

Division of Endocrinology, Cedars-Sinai Research Institute, University of California, School of Medicine, Los Angeles, California 90048, USA; IPSEN, Milford, Massachusetts 01757, USA

* To whom correspondence should be addressed. E-mail: melmed{at}csmc.edu.

Dopamine regulates both PRL secretion and gene expression whereas somatostatin (SRIF) inhibits GH secretion with unclear effects on GH gene expression. We therefore tested the effects of SRIF analogs and chimeric somatostatin-dopamine (SRIF/DA) compounds BIM 23A760 and BIM 23A761 on GH and PRL secretion and gene expression in primary rat pituitary cultures and pituitary tumor GH3 and MMQ cells.

Chimeric SRIF/DA molecules suppressed GH release with a similar efficacy to SST2 agonists in rat pituitary and GH3 cells. After 24 h BIM 23A760 and BIM 23A761 did not exert additive effects on GH secretion, and after 48 h were less effective then the combination of respective mono-receptor agonists in GH3 cells. Real-time PCR did not reveal changes in GH mRNA levels after treatment with SRIF analogs and SRIF/DA molecules. SRIF/DA compounds suppressed PRL and PRL mRNA in rat pituitary and MMQ cells with a similar efficacy to D2D receptor agonist. In GH3 cells they suppressed PRL and PRL mRNA levels with a similar efficacy to SST2 agonists. SRIF/DA molecules did not exhibit additive effects on PRL secretion and mRNA levels as compared with co-treatment with mono-receptor ligands. The results show that SRIF analogs and SRIF/DA molecules inhibit GH and PRL secretion and suppress PRL but not GH gene expression.
Key words: somatostatin analogs • dopamine • growth hormone • prolactin • pituitary tumors




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