Estrogen Upregulates T-Type Calcium Channels in the Hypothalamus and Pituitary

Abstract

Low voltage-activated (T-type) Ca2ϩ channels are responsible for generating low-threshold spikes (LTS) that facilitate burst firing and transmitter release in neurons. The T-type Ca 2ϩ channels contain a regulatory ␣1 subunit, and several isoforms of the ␣1 subunit (Cav3.1, 3.2, 3.3) have been cloned. The Cav 3.1 ␣1 subunit is abundantly expressed in the hypothalamus. Previously, we found that 17 ␤-estradiol (E2) increased the number of arcuate neurons expressing LTS. Therefore, we used an ovariectomized female guinea pig model to measure the distribution and regulation of Cav3.1 mRNA expression by E2. Guinea pig Cav3.1 ␣1 subunit sequences, which were cloned by PCR, were used in ribonuclease protection (RPA) and in situ hybridization assays to evaluate mRNA expression. Based on a RPA, E2 significantly increased the mRNA expression of Cav3.1 ␣1 subunit in the mediobasal hypothalamus and the pituitary. In situ hybridization analysis revealed that E2 significantly increased Cav 3.1 mRNA expression in medial preoptic nuclei, bed nuclei stria terminalis, and the arcuate nucleus. Whole-cell patch recordings in arcuate neurons revealed that E2 treatment significantly increased the peak T-type Ca 2ϩ current density by twofold without affecting the activation/inactivation characteristics and augmented the rebound excitation by threefold to fourfold. These results suggest that estrogen regulates the mRNA expression of T-type calcium channels, which leads to increased functional expression of the channel. Increased expression of T-type channels could be one mechanism by which estrogen augments burst firing and transmitter release in hypothalamic neurons.

Identification of estradiol/ERα-regulated genes in the mouse pituitary

“…In addition, selection of these genes was supported by the known function of their encoded proteins in other tissues. Cacna1g was chosen on the basis of its well-established regulation of ion transport, which has been thought to be an important regulatory mechanism in release of hormones and neurotransmitters (Douglas & Rubin 1961, Stojilkovic et al 2005, Qiu et al 2006, Stojilkovic 2006, and has previously been reported to be under estrogenic regulation in the pituitary (Bosch et al 2009). Aebp1 has been shown to be estrogen/ERa-regulated in other tissues (Zhang et al 2005).…”

Membrane-initiated estrogen signaling in hypothalamic neurons

“…Studies are forthcoming on the cross-talk between rapid membrane-initiated and long-term nuclear-initiated steroid actions (Lagrange et al, 1994, Lagrange et al, 1997, Wagner et al, 2001b, Vasudevan et al, 2001, Kow and Pfaff, 2004, Malyala et al, 2005, Qiu et al, 2006b, Qiu et al, 2006a, Roepke et al, 2007. For example, it has been found that both acute effects of E2 and the transcriptional changes alter excitability of hypothalamic neurons , Malyala et al, 2005, Qiu et al, 2006a.…”

“…For example, it has been found that both acute effects of E2 and the transcriptional changes alter excitability of hypothalamic neurons , Malyala et al, 2005, Qiu et al, 2006a. In addition, the estrogen-induced membrane actions in the ventromedial nucleus (VMH) of the hypothalamus can potentiate its genomic effects on lordosis behavior (Kow and Pfaff, 2004).…”

Regulation of the sperm calcium channel CatSper by endogenous steroids and plant triterpenoids

“…The female hormone progesterone (P4) activates the principal calcium channel of sperm (CatSper) (2)(3)(4)(5) and blocks the potassium channel KSper (6) via these nongenomic pathways (7). The modulation of ion channel functions by steroid hormones has been reported in the heart (8,9), neurons (10)(11)(12), smooth muscle (13), and pancreatic beta cells (14). In marine invertebrates, the sulfated steroid cholestane acts as a chemoattractant for sea squirt sperm, which also happens via the nongenomic pathway (15).…”