Regulation of growth hormone and prolactin gene expression and secretion by chimeric somatostatin-dopamine molecules.
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 GH(3) and MMQ cells. Chimeric SRIF/DA molecules suppressed GH release with a similar efficacy to SRIF receptor subtype 2 agonists in rat pituitary and GH(3) 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 GH(3) 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 D(2)-DA receptor agonist. In GH(3) 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.
Division of Endocrinology, Cedars-Sinai Research Institute, University of California School of Medicine, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA.
Anna
A
Gruszka
Song-Guang
SG
Ren
Jesse
J
Dong
Michael D
MD
Culler
Shlomo
S
Melmed
D000818:Animals; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004298:Dopamine / Q000235:genetics / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D013006:Growth Hormone / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D010902:Pituitary Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011388:Prolactin / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D017481:Receptors, Somatostatin / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013004:Somatostatin / Q000031:analogs & derivatives / Q000235:genetics / Q000494:pharmacology
C519495:BIM 23120; D018491:Dopamine Agonists; D012333:RNA, Messenger; D017448:Receptors, Dopamine D2; D017481:Receptors, Somatostatin; D011993:Recombinant Fusion Proteins; D013004:Somatostatin; D011388:Prolactin; D013006:Growth Hormone; D004298:Dopamine