Menstruation Research Today is a free monthly online journal that collates and summarizes the latest research about Menstruation, including details on menstrual cycle, pregnancy, pain, irregular menstruation.

Pharmacological inhibition of phosphodiesterase 4 triggers ovulation in follicle-stimulating hormone-primed rats.

McKenna SD, Pietropaolo M, Tos EG, Clark A, Fischer D, Kagan D, Bao B, Chedrese PJ, Palmer S

Serono Reproductive Biology Institute, Rockland, Massachusetts 02370, USA. sean.mckenna@serono.com

Phosphodiesterases (PDEs) are a family of enzymes that hydrolyze cyclic nucleotides to render them biologically inactive. As such, these enzymes are critical regulators of signal transduction pathways that use cyclic nucleotides as second messengers. PDE4 is one such member that has been identified in ovarian tissue and purported to have a role in the regulation of gonadotropin action. In the present study, selective PDE4 inhibitors enhanced intracellular signaling in a human LH receptor-expressing granulosa cell line. In vivo, PDE4 inhibition in FSH-primed rats resulted in ovulation, indicating that the PDE4 inhibitors can substitute for LH and human chorionic gonadotropin (hCG) in this process. Moreover, when coadministered with a subeffective dose of hCG, PDE4 inhibitors acted synergistically to enhance the ovulation response. Inhibitors of PDE3 or PDE5 had no ovulatory effect under similar conditions. Oocytes that were ovulated after PDE4 inhibition could be fertilized in vitro at a rate similar to that of oocytes from hCG-induced ovulation. Moreover, such oocytes were fully capable of being fertilized in vivo and developing into normal live pups. These results indicate that small molecule PDE4 inhibitors may be orally active alternatives to hCG as part of a fertility treatment regimen.

Published 16 December 2004 in Endocrinology, 146(1): 208-14.
Full-text of this article is available online (may require subscription).

© 2004-2008 Menstruation Research Today. All Rights Reserved.