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Normal anterior pituitary function is essential for fertility. Release from the gland of the reproductive hormones LH and FSH is regulated primarily by hypothalamically-derived gonadotropin releasing hormone (GnRH), although other releasing factors have been postulated to exist. Using a bioinformatic approach, we have identified a novel peptide, phoenixin, that regulates pituitary gonadotropin secretion by modulating expression of the GnRH receptor, an action with physiologically relevant consequences. Compromise of phoenixin in vivo using siRNA resulted in the delayed appearance of oestrus and a reduction in GnRH receptor expression in the pituitary. Phoenixin may represent a new class of hypothalamically-derived pituitary priming factors (PFs) that sensitise the pituitary to the action of other RFs, rather than directly stimulating the fusion of secretory vesicles to pituitary membranes.

Nesfatin-1 is a recently discovered hypothalamic peptide that was shown to suppress food intake through a melanocortin-3/4 receptor-dependent mechanism. Since nesfatin-1 mRNA is detected in the paraventricular nucleus of the hypothalamus, and because many peptides that alter food intake also influence cardiovascular function, we tested the ability of centrally administered nesfatin-1 to affect mean arterial pressure (MAP) in conscious, freely moving rats. Significant increases in MAP were observed following intracerebroventricular administration of nesfatin-1. Pretreatment with either the melanocortin-3/4 receptor antagonist, SHU9119 (intracerebroventricular), or the alpha-adrenergic antagonist, phentolamine (intra-arterial), abrogated the rise in MAP induced by nesfatin-1, indicating that nesfatin-1 may interact with the central melanocortin system to increase sympathetic nerve activity and lead to an increase in MAP. Thus we have identified a novel action of nesfatin-1, in addition to its anorexigenic effects, to stimulate autonomic nervous system activity.

Background-The paraventricular nucleus of the hypothalamus (PVN) has emerged as one of the most important autonomic control centers in the brain, with neurons playing essential roles in controlling stress, metabolism, growth, reproduction, immune, and other more traditional autonomic functions (gastrointestinal, renal and cardiovascular).Objectives-Traditionally the PVN was viewed very much as a nucleus in which afferent inputs from other regions were faithfully translated into changes in single specific outputs whether those were neuroendocrine or autonomic. Here we will present data which suggest that PVN in fact plays significant and essential roles in integrating multiple sources of afferent input and sculpting an integrated autonomic output by concurrently modifying the excitability of multiple output pathways. In addition we will highlight recent work which suggests that dysfunction of such intranuclear integrative circuitry may contribute to the pathology of conditions such as hypertension and congestive heart failure.Conclusions-This review highlights data showing that individual afferent inputs (SFO), signaling molecules (orexins, adiponectin), and interneurons (glutamate/GABA), all have the potential to influence (and thus coordinate) multiple PVN output pathways. We also highlight recent studies showing that modifications in this integrated circuitry may play significant roles in the pathology of diseases such as congestive heart failure and hypertension.