Secretin: a neurosecretory factor regulating body water homeostasis

Abstract

Vasopressin (Vp) and oxytocin (Oxt) are generally accepted to be the only two neurosecretory hormones that are released from the posterior pituitary into the systemic circulation. However, recent findings from our group showed that secretin, originally isolated from the upper intestinal mucosal extract, is abundantly expressed in the hypothalamic magnocellular neurons and is also a neuro-secretory hormone that is released from the posterior pituitary into the systemic circulation under plasma hyperosmolality conditions. Using secretin-null (SCT-/-) and secretin receptor-null (SCTR-/-) mice, we found that mutation of either genes could alter the expression and release of Vp under plasma hyperosmolality. Additionally, reduction in the renal expression of water channels including aquaporin-2 and aquaporin-4, as well as altered glomerular and tubular morphology, were also observed in these transgenic littermates. Together with the findings that secretin could (1) act as a dipsogenic agent when injected intracerebroventricularly and (2) directly stimulate the expression and translocation of the aquaporin-2 in the renal medullary tubules, we propose here that the peptide could work at multiple levels in the subfornical organ-hypothalamopituitary-kidney axis to regulate body water homeostasis. These findings not only challenge our previous understanding regarding the neuroanatomy of neurohypophysis, but also provide information for at least one of the Vp-independent mechanisms that modulate the process of renal water reabsorption. Future investigations in this direction should be important in developing therapeutic means for treating Xlinked nephrogenic diabetes insipidus by therapeutically bypassing the dysfunctional Vp receptors.