17β‐estradiol regulation of the mRNA expression of t‐type calcium channel subunits: Role of estrogen receptor α and estrogen receptor β

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 α1 subunit, of which there are three subtypes, Cav3.1, ‐3.2, and ‐3.3, and each subtype has distinct kinetic characteristics. Although 17β‐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 ERα‐ and ERβ‐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 ERα, whereas the E2 effect on Cav3.2 was dependent on both ERα and ERβ. However, the E2‐induced effects in the pituitary were dependent on only the expression of ERα. 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. J. Comp. Neurol. 512:347–358, 2009. © 2008 Wiley‐Liss, Inc.