Modulation of estrogen receptor by insulin and its biologic significance.
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.
D000818:Animals; D006224:Cricetinae; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D005260:Female; D007328:Insulin / Q000494:pharmacology*; D011960:Receptors, Estrogen / Q000187:drug effects* / Q000378:metabolism; D013311:Streptozocin; D014594:Uterine Neoplasms / Q000378:metabolism* / Q000473:pathology
D007328:Insulin; D011960:Receptors, Estrogen; D013311:Streptozocin