Dataset Information

Estrogen upregulates T-type calcium channels in the hypothalamus and pituitary.

ABSTRACT: Low voltage-activated (T-type) Ca2+ channels are responsible for generating low-threshold spikes (LTS) that facilitate burst firing and transmitter release in neurons. The T-type Ca2+ channels contain a regulatory alpha1 subunit, and several isoforms of the alpha1 subunit (Cav3.1, 3.2, 3.3) have been cloned. The Cav 3.1 alpha1 subunit is abundantly expressed in the hypothalamus. Previously, we found that 17 beta-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 alpha1 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 alpha1 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 Ca2+ 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.

SUBMITTER: Qiu J

PROVIDER: S-EPMC6674650 | biostudies-literature | 2006 Oct

REPOSITORIES: biostudies-literature

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Estrogen upregulates T-type calcium channels in the hypothalamus and pituitary.

Qiu Jian J Bosch Martha A MA Jamali Khalid K Xue Changhui C Kelly Martin J MJ Rønnekleiv Oline K OK

The Journal of neuroscience : the official journal of the Society for Neuroscience 20061001 43

Low voltage-activated (T-type) Ca2+ channels are responsible for generating low-threshold spikes (LTS) that facilitate burst firing and transmitter release in neurons. The T-type Ca2+ channels contain a regulatory alpha1 subunit, and several isoforms of the alpha1 subunit (Cav3.1, 3.2, 3.3) have been cloned. The Cav 3.1 alpha1 subunit is abundantly expressed in the hypothalamus. Previously, we found that 17 beta-estradiol (E2) increased the number of arcuate neurons expressing LTS. Therefore, we ...[more]

PMID: 17065449

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Project description:Purpose: To detect the presence of antipituitary (APA) and antihypothalamus antibodies (AHA) in subjects treated for brain cancers, and to evaluate their potential association with pituitary dysfunction. Methods: We evaluated 63 patients with craniopharyngioma, glioma, and germinoma treated with surgery and/or radiotherapy and/or chemotherapy at a median age of 13 years. Forty-one had multiple pituitary hormone deficiencies (MPHD), six had a single pituitary defect. GH was the most common defect (65.1%), followed by AVP (61.9%), TSH (57.1%), ACTH (49.2%), and gonadotropin (38.1%). APA and AHA were evaluated by simple indirect immunofluorescence method indirect immunofluorescence in patients and in 50 healthy controls. Results: Circulating APA and/or AHA were found in 31 subjects (49.2%) and in none of the healthy controls. In particular, 25 subjects out of 31 were APA (80.6%), 26 were AHA (83.90%), and 20 were both APA and AHA (64.5%). Nine patients APA and/or AHA have craniopharyngioma (29%), seven (22.6%) have glioma, and 15 (48.4%) have germinoma. Patients with craniopharyngioma were positive for at least one antibody in 39.1% compared to 33.3% of patients with glioma and to 78.9% of those with germinoma with an analogous distribution for APA and AHA between the three tumors. The presence of APA or AHA and of both APA and AHA was significantly increased in patients with germinoma. The presence of APA (P = 0.001) and their titers (P = 0.001) was significantly associated with the type of tumor in the following order: germinomas, craniopharyngiomas, and gliomas; an analogous distribution was observed for the presence of AHA (P = 0.002) and their titers (P = 0.012). In addition, we found a significant association between radiotherapy and APA (P = 0.03). Conclusions: Brain tumors especially germinoma are associated with the development of hypothalamic-pituitary antibodies and pituitary defects. The correct interpretation of APA/AHA antibodies is essential to avoid a misdiagnosis of an autoimmune infundibulo-neurohypophysitis or pituitary hypophysitis in patients with germinoma.

Dataset Information

Estrogen upregulates T-type calcium channels in the hypothalamus and pituitary.

Publications

Estrogen upregulates T-type calcium channels in the hypothalamus and pituitary.

Similar Datasets

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