Suppression of a pituitary-ovarian axis by chronic oral administration of a novel nonpeptide gonadotropin-releasing hormone antagonist, TAK-013, in cynomolgus monkeys

Takahito Hara, Hideo Araki, Masami Kusaka, Masataka Harada, Nobuo Cho, Nobuhiro Suzuki, Shuichi Furuya, Masahiko Fujino

Research output: Contribution to journalArticlepeer-review

32 Citations (Scopus)

Abstract

TAK-013 is a novel nonpeptide and orally active GnRH antagonist. We first examined the effect of TAK-013 on GnRH-stimulated LH release using primary-cultured pituitary cells of cynomolgus monkeys. TAK-013 suppressed LH release to below basal levels at concentrations higher than 100 nM with the IC50 value of 36 nM. Next, we examined the effect of chronic oral administration of TAK-013 on serum hormone levels in regularly cycling female cynomolgus monkeys. TAK-013 administered at 90 mg/kg·d (30 mg/kg 3 times daily) for approximately 80 d continued to suppress LH, estradiol, and progesterone, but not FSH. The suppressive effect was reversible, in that normal profiles of sex steroids were observed immediately after discontinuation of the TAK-013 treatment. Interestingly, the suppressive effect of TAK-013 was not observed in marmoset monkeys. In summary, TAK-013 by oral administration suppresses a pituitary-ovarian axis continuously and reversibly in cynomolgus monkeys. Considering that TAK-013 has more potent antagonistic properties for human GnRH receptor than for monkey receptor, our data suggest that TAK-013 would be effective for reproductive disorders such as endometriosis and uterine leiomyoma and useful for assisted reproductive technology procedures.

Original languageEnglish
Pages (from-to)1697-1704
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Volume88
Issue number4
DOIs
Publication statusPublished - Apr 1 2003
Externally publishedYes

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Fingerprint Dive into the research topics of 'Suppression of a pituitary-ovarian axis by chronic oral administration of a novel nonpeptide gonadotropin-releasing hormone antagonist, TAK-013, in cynomolgus monkeys'. Together they form a unique fingerprint.

Cite this