A synthetic peptide derived from mouse pituitary calcitonin cDNA sequence exhibits potent inhibition of prolactin secretion and prolactin mRNA abundance in primary mouse pituitary cells.
We have shown that gonadotrophs synthesize and secrete immunoreactive calcitonin (CT)-like peptide, and CT is a potent inhibitor of prolactin (PRL) secretion and gene transcription. CT cDNA cloned from LssT2 cells (pit-CT cDNA) exhibits 99% homology with mouse CT cDNA sequence, but exhibits four mismatches in the coding region of CT peptide (347-485 bp) with consequent changes in the amino acids at positions 5 and 17 of mouse CT. We have synthesized a putative 23 amino acid pit-CT peptide based on pit-CT cDNA sequence, and tested its effect on PRL secretion and mRNA abundance in primary mouse pituitary cells. The results suggest that synthetic pit-CT attenuates PRL mRNA abundance and inhibits PRL release from mouse anterior pituitary cells. Moreover, pit-CT is remarkably more potent than salmon (S)CT in attenuating PRL mRNA abundance. These results raise a possibility that this endogenous pituitary peptide may potentially serve as a therapeutic molecule for the treatment of prolactinomas.
Kulkarni-Paranjape
Trupti
T
Department of Pharmaceutical Sciences, College of Pharmacy, University Of Louisiana, 700 University Avenue, Monroe, LA 71209, USA.
Shah
Girish V
GV
D000595:Amino Acid Sequence; D000818:Animals; D002116:Calcitonin / Q000138:chemical synthesis / Q000235:genetics / Q000494:pharmacology*; D002478:Cells, Cultured; D003001:Cloning, Molecular; D018076:DNA, Complementary; D005260:Female; D051379:Mice; D008969:Molecular Sequence Data; D010902:Pituitary Gland / Q000378:metabolism; D011388:Prolactin / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000187:drug effects
D018076:DNA, Complementary; D012333:RNA, Messenger; C028815:salmon calcitonin; D011388:Prolactin; D002116:Calcitonin