Dilip Mukherjee
University of Kalyani, India
Title: Novel expression of functional cytochrome P450arom mRNA and its induction by LH for de novo synthesis of estrogen in nonpregnant mice endometrium
Biography
Biography: Dilip Mukherjee
Abstract
Presence and activation of aromatase enzyme and its physiological relevance in mammalian uterus including human have been previously reported. Local estrogen production in human endometrium also was suggested to be important in development of cancer. However, the presence or absence of aromatase cytochrome P450arom (P45arom) transcript and aromatase enzyme in the endometrium of normal human and other mammals is controversial. To address this issue, we used RT-PCR and real time PCR techniques to evaluate the presence or absence of P450arom transcript and its physiological significance in endometrial tissues of non-pregnant mice under various culture conditions. Endometrium at metestrus stage of estrous cycle contained P450arom mRNA, essentially identical to that found in mouse ovary and LH caused significant increase in its expression levels. Endometrium also contained aromatase activity as evident from increased conversion of labeled testosterone to 17β-estradiol (E2) and de novo E2 synthesis. Non-steroidal inhibitor fadrozole significantly attenuated both aromatase activity and E2 synthesis. Most interesting finding was the inhibition of P450arom gene expression in vitro by fadrozole. LH-induced endometrial E2 synthesis was mediated through activation of steroidogenic factor-1 protein. Matrix metalloproteinases (MMPs) are expressed in the mice endometrium. We examined the steroidal regulation of MMP9 within mouse endometrium. Female mice were ovariectomized and treated with LH and E2 alone or E2 plus progesterone (P4) and MMP9 gene expression were studied. Results revealed that LH and E2 alone or E2 plus P4 increase MMP9 gene expression. All these findings are indicative of the presence of functional P450arom mRNA and its stimulation by LH leading to E2 synthesis in non-pregnant mouse endometrium. Results also suggest that E2 synthesis by the induction of LH in mouse endometrium regulates MMP9 expression and activity in vivo via a complex mechanism. This estrogen regulation of MMP9 may play an important role in uterine tissue remodeling.