Physiological action of progesterone in target tissues

Examination of the regulation of gene expression by progesterone has revealed the complexity of the diverse roles of this hormone in the control of female reproductive function. The actions of progesterone have been characterized in the most detail in the uterus, where progesterone participates in the cyclical control of proliferation and differentiation during the menstrual cycle and plays a key role in pregnancy, being involved in ovulation, implantation, uterine growth, and maintenance of pregnancy. In the uterus, progesterone both stimulates and inhibits cell proliferation. It promotes differentiated function and, although the mechanisms underlying progesterone opposition of estrogen action have been investigated, most of the mechanisms underlying the diverse roles of progesterone in the uterus still require elucidation. In the breast, progesterone is primarily responsible for development of the lobular-alveolar structures during puberty and pregnancy, but also plays a role in cyclical control of proliferation during the menstrual cycle by mechanisms that are poorly understood. In the brain, the effects of progesterone on sexually receptive behavior have been established in animal studies, but information on the role of progesterone in the human brain is limited. Similarly, although progesterone is likely to play a role in bone remodeling, there is s paucity of information on this at present. The molecular mechanisms of progesterone action have been described only for a small number of well defined target genes, examples being the uteroglobin and ovalbumin genes, which have been studied in detail. However, progesterone is clearly involved in the regulation of a considerable number of genes about which little is known. Furthermore, the distinction between direct and indirect targets of progesterone action in cellular processes is largely yet to be made. By separating gene-regulatory events, which are central to the physiological effects of progesterone, from the secondary consequences of progesterone action, it may be possible to define the determinants of response to progesterone in normal and malignant cells.