Luteinizing hormone is a primary culprit in the endometrial carcinoma development in elderly women

Abstract

Endometrial carcinomas (ECs) are the most common gynecologic malignancies, exceeding the incidence of ovarian and cervical cancers in elderly women (post-menopausal) in Western countries. Evidence suggests that it is a luteinizing hormone (LH) dependent disease. ECs overexpress LH/human chorionic gonadotropin (hCG) receptors as compared with pre and post-menopausal endometria. Activation of the LH/hCG receptors in primary and immortalized EC cells results in an increased cell proliferation and invasion, which are mediated by cyclic AMP(cAMP)/protein kinase A (PKA) signaling, require the presence of LH/hCG receptors, activation of β₁ integrin receptors and an increase in the secretion of metalloproteinase-2 (MMP-2) in its active form. In addition to the endometrium, LH actions in the ovaries and adrenal glands results in an increased secretion of androgens, which are aromatized into estrogens in the adipose and EC tissues. LH also has direct effects in the pancreas, which results in an increase in insulin secretion, which in turn can also stimulate ovarian stromal cell proliferation, luteinization, androgens secretion and aromatization in adipose and EC tissues. LH is further elevated in post-menopausal women who develop EC as compared with post-menopausal women who do not develop the disease. These findings support complex network of LH actions that promote EC development in elderly women.