Targeted cytotoxic analogue of luteinizing hormone-releasing hormone (LH-RH) only transiently decreases the gene expression of pituitary receptors for LH-RH

Journal of Neuroendocrinology
M KovacsA Nagy

Abstract

A cytotoxic analogue of LH-RH, AN-207, consisting of 2-pyrrolinodoxorubicin (AN-201) linked to carrier [D-Lys6]LH-RH, was developed for targeted therapy of cancers expressing LH-RH-receptors. To determine its possible side-effects on the pituitary gland, we investigated the gene expression of pituitary LH-RH-receptors and LH secretion in ovariectomized female and normal male rats after treatment with the maximum tolerated dose of AN-207. The effect of AN-207 on the gene expression of the pituitary GH-RH-receptors and GH secretion was also assessed in male rats. Five hours after a single i.v. injection of AN-207 at 175 nmol/kg, there was a 39-51% decrease in mRNA expression for the pituitary LH-RH-receptors in male and female rats. The carrier, at an equimolar dose, caused a similar reduction (37-39%), whereas the cytotoxic radical AN-201, at an equitoxic dose (110 nmol/kg), produced only a 12-24% decrease (NS) in the mRNA expression of LH-RH-receptors. AN-207 and the carrier analogue induced a comparable 90-100-fold increase in serum LH concentrations in male rats, and the same 12-fold elevation in OVX rats at 5 h. Seven days after treatment with AN-207, the mRNA levels for the LH-RH receptors and the serum LH concentration wer...Continue Reading

References

Dec 30, 1992·Biochemical and Biophysical Research Communications·U B KaiserW W Chin
Jan 1, 1991·Pharmacology & Therapeutics·T R Tritton
Jul 9, 1996·Proceedings of the National Academy of Sciences of the United States of America·A NagyJ Horvath
Feb 18, 1997·Proceedings of the National Academy of Sciences of the United States of America·M KovacsK Groot
Jul 17, 1999·European Journal of Endocrinology·A V Schally, A Nagy
Oct 6, 2001·Frontiers in Neuroendocrinology·A V SchallyG Halmos

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