Table 1.

Physiologic effects of estradiol by organ system, with receptor distribution and effects at each site*

Organ system	Receptors	Receptor distribution and function				Reference
Central nervous	ERα, ERβ, GPER	hypothalamic preoptic nucleus – thermoregulation suprachiasmatic nucleus – sleep, circadian rhythm prefrontal cortex – executive function thalamus – sensory integration basal forebrain – learning and memory amygdala – emotion and motivation raphe nucleus – serotinergic system, affect, and mood locus coeraleus – adrenergic system hippocampus – information processing, short-term memory, working memory, cholinergic activity arterial vessels and pericytes – vascular tone, endothelial function, oxidative stress and inflammatory response general – regulates glucose metabolism, increases neuronal connectivity, regulates synaptic plasticity				(11, 15, 28–30)
Peripheral nervous	GPER	spinal cord	$\}$		modulates pain sensation	(11, 15)
		dorsal root ganglia
		visceral nerves
Cardiovascular	ERα, ERβ, GPER	myocardium	$\}$			(11, 31–42)
		endothelial cells			increases contractile function
		smooth muscle			improves perfusion
		macrophages
Gastrointenstinal	ERα, ERβ	enteric nerve cells	$\}$		inhibits nitric oxide production	(25, 43–50)
		smooth muscle			mediates smooth muscle contraction
		macrophages			slows intestinal transit times increases ileal glucose uptake
Pancreas	ERα, ERβ, GPER	pancreatic islets – stimulates insulin secretion anti-inflammatory effects				(51–53)
Liver	ERα, ERβ, GPER	hepatocytes – regulates lipid biosynthesis and lipid transport anti-inflammatory effects				(11, 25, 32, 54–57)
Kidney	GPER	epithelial cells	$\}$		regulates renin-angiotensin system	(11, 58–62)
		renal tubules			regulates vascular function
Bone and articular cartilage	ERα, ERβ, GPER	osteoblasts – stimulates osteoblastogenesis osteoclasts – regulates bone resorption and remodeling chrondrocytes – regulates differentiation				(11, 63–71)
Skin	ERα, ERβ	keratinocytes		$\}$	increases skin thickness	(72)
		basal cells			enhances vascularization
		melanocytes			increases melanin production
Eye	ERα, ERβ	Retina and retinal pigment epithelium – unclear role				(73, 74)

^*ER = estrogen receptor; GPER = G-protein-coupled estrogen receptor.