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.
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