Gene array analysis of embryonic- versus adult-derived hypothalamic NPY-expressing cell lines.

Few studies have utilized microarray analysis to understand the genome wide changes involved in the development of the hypothalamus despite its overall importance to basic physiology. Gene expression profiling of immortalized, clonal hypothalamic neurons, embryonic-derived mHypoE-46 and adult-derived mHypoA-2/12, reveals that the expression of 1225 probes was significantly changed between the two neuronal models. Further comparison of the gene expression profiles identified two categories of genes that were confirmed with qRT-PCR: (i) genes implicated in the Wnt signaling pathway; and (ii) transcription factors previously implicated in the development of the central nervous system.

Neuropeptide Y induces gonadotropin-releasing hormone gene expression directly and through conditioned medium from mHypoE-38 NPY neurons.

Neuropeptide Y (NPY) regulates reproductive function at the level of the hypothalamus through control of GnRH secretion. However, the direct control of GnRH gene expression by NPY has not yet been studied. GT1-7 neurons were treated with 100 nM of NPY over a 36 h time course.

Hypothalamic cell lines to investigate neuroendocrine control mechanisms.

The hypothalamus is the control center for most physiological processes; yet has been difficult to study due to the inherent heterogeneity of this brain region. For this reason, researchers have turned towards cell models. Primary hypothalamic cultures are difficult to maintain, are heterogeneous neuronal and glial cell populations and often contain a minimal number of viable peptide-secreting neurons.

Activation of ERbeta increases levels of phosphorylated nNOS and NO production through a Src/PI3K/Akt-dependent pathway in hypothalamic neurons.

Estrogen plays a role in restoring homeostatic balance during the stress response by altering hypothalamic function and NO production in the brain. While we know that estrogen acts on the hypothalamus to stimulate the NO system through an ERbeta-dependent mechanism in neurons, the molecular mechanisms responsible for these effects are unknown. Because phosphorylation of nNOS at Ser(1412) increases nNOS activity which leads to increased NO production, we investigated the effects of ERbeta activation on nNOS phosphorylation at Ser(1412) and NO production in primary hypothalamic neurons.

Estrogen in the paraventricular nucleus attenuates L-glutamate-induced increases in mean arterial pressure through estrogen receptor beta and NO.

Estrogen (E2) acts in the brain to decrease blood pressure (BP) responses to psychological stress. A likely site for the effects of E2 is the hypothalamic paraventricular nucleus (PVN), an important regulator of autonomic functions. We studied the effects of E2 in the PVN on BP and heart rate (HR) responses to l-glutamate injections into the PVN of male urethane-anesthetized rats.

Estrogen modulates endothelial and neuronal nitric oxide synthase expression via an estrogen receptor beta-dependent mechanism in hypothalamic slice cultures.

Although it is evident that estrogen has important physiological effects in the brain, the signaling mechanisms mediating these effects remain unclear. We recently showed that estrogen mediates attenuated blood pressure responses to psychological stress in ovariectomized female rats through brain nitric oxide (NO). An area likely to mediate these effects is the hypothalamic paraventricular nucleus (PVN), because here NO exerts inhibitory effects on autonomic output to the periphery.