Biology of aromatase in the mammary gland.

While the ovaries are the principal source of systemic estrogen in the premenopausal nonpregnant woman, other sites of estrogen biosynthesis are present throughout the body and these become the major sources of estrogen beyond menopause. These sites include the mesenchymal cells of the adipose tissue and skin, osteoblasts, and perhaps chondrocytes in bone, vascular endothelial and aortic smooth muscle cells, as well as a number of sites in the brain including the medial preoptic/anterior hypothalamus, the medial basal hypothalamus and the amygdala. These extragonadal sites of estrogen biosynthesis possess several fundamental features which differ from those of the ovaries. Principally, the estrogen synthesized within these compartments is probably only biologically active at a local tissue level in a paracrine or 'intracrine' fashion. Thus the total amount of estrogen synthesized by these extragonadal sites may be small, but the local tissue concentrations achieved are probably quite high, and exert significant biological influence locally. Thus these sources of estrogen play an important but hitherto largely unrecognized, physiological and pathophysiological role.