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Regulation of Growth Hormone and Prolactin Gene Expression and Secretion by Chimeric Somatostatin-Dopamine Molecules

Division of Endocrinology (A.G., S.-G.R., S.M.), Cedars-Sinai Research Institute, University of California, School of Medicine, Los Angeles, California 90048; and IPSEN (J.D., M.D.C.), Milford, Massachusetts 01757

Address all correspondence and requests for reprints to: Shlomo Melmed, Academic Affairs, Room 2015, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, California 90048. E-mail: melmed{at}csmc.edu.

Dopamine (DA) regulates both prolactin (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 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 SRIF receptor subtype 2 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 than 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 D₂-DA receptor agonist. In GH₃ cells, they suppressed PRL and PRL mRNA levels with a similar efficacy to SRIF receptor subtype 2 agonists. SRIF/DA molecules did not exhibit additive effects on PRL secretion and mRNA levels as compared with cotreatment 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.

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