Procollagen synthesis is increased in hypothyroid rat ovary by a parallel and compensatory pathway

Collagen biosynthesis is a multistep process that starts with the transcription and translation of the individual collagen gene. It is characterized by the presence of a large number of co- and posttranslational modifications. Hydroxylysine is found only in animal proteins and mostly in collagens. Procollagen lysyl hydroxylation is the first step in collagen biosynthetic pathway and lysyl hydroxylases (Plod isoforms) are responsible for this enzymatic process. Previously we showed the down regulation of Plod isoforms in hypothyroid ovary. As hypothyroidism is a stress for normal animals, we wanted to explore whether any compensatory pathway exists to balance the reduced lysyl hydroxylation of collagen in hypothyroid rat ovary. In this report we have shown that procollagen I and III are increased in hypothyroid condition and subsequently decreased upon T(3) add-back. Heat Shock Protein-47 is a collagen-specific molecular chaperone and its existence in ovary has been documented. The genes encoding HSP-47, prolyl-4-hydroxylase-alpha and -beta (P4H-alpha and -beta) are increased in hypothyroid condition. Down regulation of lysyl hydroxylase in hypothyroid condition results less collagen formation. At the same time over production of procollagens, HSP-47 and P4H is very significant as they may compensate the damage whatsoever caused due to hypothyroidism in ovarian tissue.