Gonadotropic Regulation of Ovarian Ascorbic Acid- New Insights

Authors :

Saddad Shah Hussain, Nikki Kumari, Taruna Arora, Kambadur Muralidhar

 Abstract:

The standard in vivo bioassay for measurement of Luteinizing Hormone (LH) activity is Ovarian Ascorbic Acid Depletion Assay (OAAD) developed by Albert Parlow in 1961. This depletion was found to be, mediated by cAMP and was also Cyclohexiimide and Actinomycin D insensitive. It was also found that there was an increase in OAA following the first injection of Pregnant Mare Serum Gonadotropin (PMSG) which functions as mostly Follicle Stimulating Hormone (FSH) in heterologous animal species. L-Gulonate Dehydrogenase (L-GuDH) is a key enzyme in the biosynthesis of AA. It was observed that the specific activity of this enzyme remained unchanged following LH injection commensurate with our earlier observations with inhibitors of translation and transcription. Kinetic studies of the enzyme revealed four naturally occurring metabolites such as AA, Malonic acid, D-Glucuronic acid and L-Gulono Lactone, as good inhibitors. In silico studies of molecular docking confirmed these observations. The specific activity of the enzyme, however, was found to dramatically increase following FSH (i.e. PMSG) administration. Suspecting transcriptional regulation, microarray analysis of ovarian transcripts was done. Pathway analysis of non-phosphorylated sugar metabolism revealed that expression level of gene for L-GuDH remained unchanged following PMSG injection. Results are discussed.