Estrogen and xenoestrogen actions on endocrine pancreas: from ion channel modulation to activation of nuclear function.
17beta-Estradiol elicits a rapid opposite effect on [Ca2+]i in alpha- and beta-cells within intact islets of Langerhans. In beta-cells, physiological concentrations of the gonadal hormone decreases KATP channel activity in synergy with glucose, leading to a membrane depolarization that opens voltage-gated Ca2+ channels, potentiating Ca2+ signals. As a consequence insulin release is enhanced and transcription factor CREB is activated in a Ca(2+)-dependent manner. In glucagon-containing alpha-cells, 17beta-estradiol provokes the abolishment of Ca2+ oscillations generated by low glucose, a situation that should decrease glucagon release. In both types of cells the second messenger involved is cGMP. The estrogen receptor involved is located in the plasma membrane and has a pharmacological profile unrelated to classical estrogen receptors ERalpha and ERbeta. For that reason, it has been named non-classical membrane estrogen receptor (ncmER). Although the physiological roles of this receptor are still unknown, it may be implicated in the responses of the endocrine pancreas to the physiological and pathological changes of 17beta-estradiol.
Institute of Bioengineering, Miguel Hernández University, San Juan Campus, Carretera Alicante-Valencia Km 87, Alicante 03550, Spain. nadal@umh.es
Angel
A
Nadal
Ana B
AB
Ropero
Esther
E
Fuentes
Bernat
B
Soria
Cristina
C
Ripoll
D000818:Animals; D002118:Calcium / Q000737:chemistry / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism* / Q000502:physiology; D020013:Calcium Signaling; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004958:Estradiol / Q000502:physiology; D004967:Estrogens / Q000494:pharmacology* / Q000502:physiology; D005934:Glucagon / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D015221:Potassium Channels / Q000378:metabolism; D011960:Receptors, Estrogen / Q000502:physiology; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D015262:Xenobiotics / Q000494:pharmacology*
D015220:Calcium Channels; D017362:Cyclic AMP Response Element-Binding Protein; D004967:Estrogens; D015221:Potassium Channels; D011960:Receptors, Estrogen; D015262:Xenobiotics; D004958:Estradiol; D005934:Glucagon; D000254:Sodium-Potassium-Exchanging ATPase; D006152:Cyclic GMP; D005947:Glucose; D002118:Calcium