Modulation of estrogen receptor by insulin and its biologic significance
P. K. Chaudhuri, B. Chaudhuri and N. Patel
It has been proposed that a nonsteroidal hormone such as insulin may
directly exert an influence through estrogen receptors and alter the
biologic behavior of steroid hormone target tissue. The implication of such
a proposal is that diabetes may alter the outcome of estrogen
receptor-positive tumors such as breast or endometrial carcinomas. To
evaluate the effect of insulin on a receptor-positive tumor, we examined
the direct effect of insulin on an estrogen receptor and its subsequent
biologic effect on a receptor-positive endometrial carcinoma model in vitro
and in vivo. An in vitro experiment demonstrated that when the estrogen
receptor-positive cell line was grown in serum-free media with low insulin,
there was a loss of intracellular receptors for estrogen. This loss of
estrogen receptors was also associated with increased growth rate as
reflected by increased thymidine uptake. Similarly, in vivo experiments
demonstrated that a diabetic host with a high blood glucose level and a low
insulin level exhibited development of growth of a receptor-negative tumor
with accelerated growth rate in contrast to growth of a receptor-positive
tumor with slower growth rate in a normal host with normal serum insulin
and blood glucose levels. Data suggest that insulin may modulate the growth
of estrogen receptor-positive tumors through its direct effect on estrogen
receptors.
