Figure 2.

Proposed role of ERα, ERβ, and GPER for the regulation of body weight and maintenance of glucose homeostasis. In premenopausal women, 17β-estradiol (E₂) is the predominant estrogen released by the ovaries. The main source of estrogen in men and postmenopausal women is adipose tissue, where E₂ is converted from androgen precursors by the aromatase enzyme. E₂ has paracrine effects on adipocytes, but also acts centrally in the brain, as well as peripherally in organs regulating glucose homeostasis, such as the endocrine pancreas, liver, and skeletal muscle. Note that ERα and ERβ generally mediate opposing effects, whereas the role of GPER has only been in part investigated. In addition, insulin released by pancreatic β-cells regulates hepatic glucose production via gluconeogensis and glucose uptake in skeletal muscle, which is impaired by the action of inflammatory mediators released by adipose tissue. +, stimulatory effect; −, inhibitory effect; ?, effect unknown.