Anatomical and functional demonstration of a multisynaptic suprachiasmatic nucleus adrenal (cortex) pathway

Abstract

In view of mounting evidence that the suprachiasmatic nucleus (SCN) is directly involved in the setting of sensitivity of the adrenal cortex to ACTH, the present study investigated possible anatomical and functional connections between SCN and adrenal. Transneuronal virus tracing from the adrenal revealed first order labelling in neurons in the intermedio-lateral column of the spinal cord that were shown to receive an input from oxytocin fibres and subsequently second-order labelling in neurons of the autonomic division of the paraventricular nucleus. The latter neurons were shown to receive an input from vasopressin or vasoactive intestinal peptide (VIP) containing SCN efferents. The true character of this SCN input to second-order neurons was also demonstrated by the fact that third-order labelling was present within the SCN, vasopressin or VIP neurons. The functional presence of the SCN-adrenal connection was demonstrated by a light-induced fast decrease in plasma corticosterone that could not be attributed to a decrease in ACTH. Using intact and SCN-lesioned animals, the immediate decrease in plasma corticosterone was only observed in intact animals and only at the beginning of the dark period. This fast decrease of corticosterone was accompanied by constant basal levels of blood adrenaline and noradrenaline, and is proposed to be due to a direct inhibition of the neuronal output to the adrenal cortex by light-mediated activation of SCN neurons. As a consequence, it is proposed that the SCN utilizes neuronal pathways to spread its time of the day message, not only to the pineal, but also to other organs, including the adrenal, utilizing the autonomic nervous system.

Diminished adrenal sensitivity and ACTH efficacy in obese premenopausal women

“…Another pathway for regulating glucocorticoid secretion and sensitivity of the adrenal gland to ACTH in the human and experimental animals is the functional suprachiasmatic-adrenal neuronal pathway, which for instance is responsible for the acute rise of serum cortisol without a rise in ACTH after exposure to bright light. This pathway may be important for the modulation of the responsiveness of the adrenal gland to ACTH (26,27). A testable postulate is that this transsynaptic pathway may diminish ACTH-cortisol responsiveness in obesity with its associated increased sympathetic activity (28).…”

The regulation of neuroendocrine function: Timing is everything

“…If this means of temporal control is implemented at peripheral targets, necessary alterations in the timing of organ/gland responsiveness due to changes in local conditions can be communicated rapidly to hormone-sensitive targets to adjust the timing of their circadian clocks. Given that numerous organs (e.g., liver, pancreas) and endocrine glands (e.g., testes, adipose tissue, adrenal gland) investigated to date receive autonomic innervation from the SCN (Bamshad et al, 1998;Bartness et al, 2001;Buijs et al, 1999Buijs et al, , 2003Kalsbeek et al, 2000;Olcese et al, 2003), these multisynaptic connections may provide a rapid means of clock resetting in peripheral tissues to ensure proper reception of slower diffusible communication (Fig. 6).…”

Glucocorticoids and circadian clock control of cell proliferation: At the interface between three dynamic systems

“…Furthermore, it was shown that nocturnal light exposure can lead to changes in corticosterone release from the adrenal gland without accompanying changes in ACTH [101,102]. This effect of light upon corticosterone release was dependent on the SCN, since ablation of the SCN abolished it.…”

“…Apparently, in addition to the HPA axis pathway, an alternative neural pathway exists from the SCN to the adrenal gland (Fig.2). Transneural retrograde virus tracing showed that this pathway runs via the autonomic nervous system [97,101,103]. SCN neurons contact neurons of the preautonomic PVN, which project to the sympathetic preganglionic neurons of the spinal cord.…”