Modulation of estrogen receptor by insulin and its biologic significance

Arch Surg. 1986 Nov;121(11):1322-5. doi: 10.1001/archsurg.121.11.1322.


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.

MeSH terms

  • Animals
  • Cricetinae
  • Diabetes Mellitus, Experimental / metabolism
  • Female
  • Insulin / pharmacology*
  • Receptors, Estrogen / drug effects*
  • Receptors, Estrogen / metabolism
  • Streptozocin
  • Uterine Neoplasms / metabolism*
  • Uterine Neoplasms / pathology


  • Insulin
  • Receptors, Estrogen
  • Streptozocin