Estrogen agonists/antagonists may down-regulate growth hormone signaling in hepatocytes--an explanation for their impact on IGF-I, IGFBP-1, and lipoprotein(a).

Estrogen agonists/antagonists, when administered orally, exert a range of effects on hepatic function, some of which are potentially protective. These effects include reduced synthesis of IGF-I and apolipoprotein(a), and increased synthesis of IGFBP-1--shifts which arguably could decrease risk for vascular disease and certain cancers. These effects are diametrically opposite to those of growth hormone (GH), which boosts hepatic production of IGF-I and apolipoprotein(a), while suppressing that of IGFBP-1. Thus, a parsimonious explanation of these phenomena is that oral estrogen blunts the efficiency of GH signaling in the liver. Oral androgenic progestins may have the reverse effect. It may be of particular value to determine whether certain estrogen agonists/antagonists can exert relatively 'hepatospecific' activity when administered orally--thus enabling down-regulation of systemic IGF-I activity and of lipoprotein(a), without however inducing a significant increase in systemic estrogen activity. Preliminary evidence suggests that flax lignans and perhaps other phytoestrogens may have potential in this regard.