Regulation of angiogenic factors TIMP-1, CTGF and Mac25 by chorionic gonadotropin in human granulosa lutein cells

As prerequisite for development and maintenance of many diseases angiogenesis is of particular interest in medicine. Pathologic angiogenesis takes place in chronic arthritis, collagen diseases, arteriosclerosis, retinopathy associated with diabetes, and in particularly in cancers.

In the ovarian corpus luteum angiogenesis regularly occurs as a physiological and particulary a controlled process, even more intensively than in any known tumor. This angiogenesis strongly depends on ovarian cycles and sexual steroid hormones. Attempting to understand the regulatory mechanisms of angiogenesis in the human ovary we studied the influence of hCG on the expression and production of angiogenic factors in human granulosa lutein cells in cell culture.

In particular we determined the expression and production of several angiogenic factors including TIMP-1, Leptin, CTGF, Mac25, bFGF and Midkine. In addition we showed that hCG has distinct effects on their expression and production. hCG enhances the expression and production of TIMP-1, whereas it down-regulates the expression of CTGF and Mac25. Furthermore it decreases the expression of Leptin. Our results provide evidence that hCG determines growth and development of the corpus luteum by mediating angiogenic pathways in human granulosa lutein cells. Hence we describe a further approach to understand the regulation of angiogenesis in the ovary.