Sex‐specific differences in cardiovascular and metabolic hormones with integrated signalling in the paraventricular nucleus of the hypothalamus

Abstract

What is the topic of this review? We describe roles of crucial signalling molecules in the paraventricular nucleus of the hypothalamus and highlight recent data suggesting sex-specific changes in the expression of crucial signalling molecules and their receptors, which may underlie sex differences in both cardiovascular and metabolic function. What advances does it highlight? This review highlights the integrative capacity of the paraventricular nucleus in mediating cardiovascular and metabolic effects by integrating information from multiple signalling molecules. It also proposes that these signalling molecules have sex-specific differential gene expression, indicating the importance of considering these differences in our ongoing search to understand the female-male differences in the regulation of crucial autonomic systems. Many traditional cardiovascular hormones have been implicated in metabolic function. Conversely, many hormones traditionally involved in metabolic regulation have an effect on cardiovascular function. Many of these signalling molecules exert such effects through specific actions in the paraventricular nucleus, an integrative autonomic control centre located in the hypothalamus. Here, we focus on four cardiovascular/metabolic peptide hormones that signal within the paraventricular nucleus, namely angiotensin II, orexin, adiponectin and nesfatin-1. Each of these hormones has specific electrophysiological effects on paraventricular nucleus neurons that can be related to its physiological actions. In addition, we introduce preliminary transcriptomic data indicating that the genes for some of these hormones and their receptors have sex-specific differential expression.

Sushi repeat‐containing protein X‐linked 2: A novel phylogenetically conserved hypothalamo‐pituitary protein

“…In rat brain, all SRPX2‐ir neurons were located in the hypothalamus (Figure a), particularly in the Pa, Pe (Figure a 1 ), and SO nuclei (Figure a 2 ). In the Pa, SRPX2‐ir neurons were distributed bilaterally in all functional compartments within the nucleus, including the neurosecretory magnocellular neurons, endocrine, and pre‐autonomic parvocellular neurons (Ferguson, Latchford, & Samson, ; Loewen et al, ; Swanson & Sawchenko, ). The cytoplasmic SRPX2 protein had a granular appearance when observed at a higher magnification (Figure c).…”

“…Most of the SRPX2‐ir neurons were located in the Pa, which has three functional compartments. These include the neurosecretory magnocellular neurons projecting to the posterior pituitary, the neuroendocrine parvocellular neurons projecting to the median eminence, and the pre‐autonomic parvocellular neurons projecting to the nucleus tractus solitarius, rostral ventrolateral medulla, and spinal cord (Ferguson et al, ; Loewen et al, ; Swanson & Sawchenko, ). This explains the observed topographic organization of SRPX2‐ir projections to the hypophysis and brainstem.…”

Cardiac Autonomic Neuropathy as a Result of Mild Hypercaloric Challenge in Absence of Signs of Diabetes: Modulation by Antidiabetic Drugs

“…A potential link with CAN could be established considering the effect of adipose hormones on central neuronal activity. Among the adipokines, adiponectin and nesfatin have been found to exert metabolic and cardiovascular regulatory functions within the hypothalamic paraventricular nucleus [ 77 ]. Hence, it would be reasonable to assume that an alteration in the adipokine profile caused by adipose inflammation would have an impact on central neuronal function.…”

Orexins and stress

“…Regardless, food and drug seeking behavior engages the orexin system differentially in males and females. Further support for increased orexin function in females comes from a recent study in which OX 2 R expression in the PVN was found to be higher in female rats compared with male rats (Loewen et al, 2017). Increased OX 2 R expression might suggest increased orexin action at the apex of the HPA response; this might explain, in part, how orexins exacerbate the response to stress in female rats.…”