title: 17Beta-estradiol regulation of the mRNA expression of T-type calcium channel subunits: role of estrogen receptor alpha and estrogen receptor beta.
abstract: Low-voltage-activated (T-type) calcium channels are responsible for burst firing and transmitter release in neurons and are important for exocytosis and hormone secretion in pituitary cells. T-type channels contain an alpha1 subunit, of which there are three subtypes, Cav3.1, -3.2, and -3.3, and each subtype has distinct kinetic characteristics. Although 17beta-estradiol (E2) modulates T-type calcium channel expression and function, little is known about the molecular mechanisms involved. We used real-time PCR quantification of RNA extracted from hypothalamic nuclei and pituitary in vehicle and E2-treated C57BL/6 mice to elucidate E2-mediated regulation of Cav3.1, -3.2, and -3.3 subunits. The three subunits were expressed in both the hypothalamus and the pituitary. E2 treatment increased the mRNA expression of Cav3.1 and -3.2, but not Cav3.3, in the medial preoptic area and the arcuate nucleus. In the pituitary, Cav3.1 was increased with E2 treatment, and Cav3.2 and -3.3 were decreased. To examine whether the classical estrogen receptors (ERs) were involved in the regulation, we used ERalpha- and ERbeta-deficient C57BL/6 mice and explored the effects of E2 on T-type channel subtypes. Indeed, we found that the E2-induced increase in Cav3.1 in the hypothalamus was dependent on ERalpha, whereas the E2 effect on Cav3.2 was dependent on both ERalpha and ERbeta. However, the E2-induced effects in the pituitary were dependent on only the expression of ERalpha. The robust E2 regulation of T-type calcium channels could be an important mechanism by which E2 increases the excitability of hypothalamic neurons and modulates pituitary secretion.
authors.affiliation: Department of Physiology and Pharmacology, Oregon Health and Science University, Portland, Oregon 97239, USA.
authors.forename: Martha A
authors.initials: MA
authors.lastname: Bosch
authors.forename: Jingwen
authors.initials: J
authors.lastname: Hou
authors.forename: Yuan
authors.initials: Y
authors.lastname: Fang
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Kelly
authors.forename: Oline K
authors.initials: OK
authors.lastname: Rønnekleiv
mesh_terms: D000818:Animals; D020747:Calcium Channels, T-Type / Q000235:genetics / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism*; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism*; D005260:Female; D007031:Hypothalamus / Q000033:anatomy & histology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009929:Organ Size; D010902:Pituitary Gland / Q000033:anatomy & histology / Q000378:metabolism; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D014599:Uterus / Q000033:anatomy & histology
chemical_list: C534770:Cacna1i protein, mouse; D020747:Calcium Channels, T-Type; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D021122:Protein Subunits; D012333:RNA, Messenger; D004958:Estradiol