Expression of α(1D) adrenergic receptor messenger rna in oxytocin- and corticotropin-releasing hormone-synthesizing neurons in the rat paraventricular nucleus

The paraventricular nucleus of the hypothalamus contains a number of intermingled populations of neuroendocrine cell groups involved in the hormonal stress response, including cells synthesizing corticotropin- releasing hormone and oxytocin. Ascending noradrenergic afferents to the paraventricular nucleus, acting through α₁ adrenergic receptors, are thought to play a role in stress-induced activation of the hypothalamic- pituitary-adrenal axis. We have previously demonstrated that, of the three known α₁ adrenergic receptor subtypes, messenger RNA for the α(1D) subtype is the most prominently expressed in the paraventricular nucleus. Thus, regulation of the expression of this receptor may be important in modulation of the stress response. It is currently unknown, however, which populations of stress-related neuroendocrine cells in the paraventricular nucleus express α₁ receptors, or whether the excitatory influence of norepinephrine in stress is exerted directly on neurons expressing oxytocin or corticotropin- releasing hormone. Thus, in the present study, we used dual in situ hybridization, combining a digoxigenin-labeled riboprobe encoding the rat α(1D) adrenergic receptor with radiolabeled riboprobes for oxytocin or corticotropin-releasing hormone, to determine the degree to which these neurons in the paraventricular nucleus express α(1D) adrenergic receptors. In sections through the rostral and mid-level paraventricular nucleus, nearly all (>95%) oxytocin neurons also expressed α(1D) messenger RNA. In contrast, the populations of corticotropin-releasing hormone- and α(1D)-expressing cells overlapped only partially, with most α(1D) expression situated more laterally. A subset (37%) of the neurons expressing corticotropin-releasing hormone also expressed α(1D) messenger RNA, and these were found almost entirely within the region of overlap in the lateral aspect of the medial parvocellular region. These observations support a direct role for α₁ receptors in regulation of oxytocin secretion. Expression of α(1D) messenger RNA in distinct subsets of cells synthesizing corticotropin-releasing hormone may also help to clarify contradictory and inconsistent observations in the literature regarding the role of norepinephrine in the stress response, and may account for a presumed stressor-specific role for norepinephrine in activation of the hypothalamic-pituitary-adrenal axis.