CRF and stress in fish

Abstract

The endocrine stress response is pivotal in vertebrate physiology. The stress hormone cortisol-the end product of the endocrine stress axis-(re-)directs energy flows for optimal performance under conditions where homeostasis may be or become at risk. Key players in the continuous adaptation process are corticotropin-releasing factor (CRF) from the hypothalamic nucleus preopticus (NPO), pituitary adrenocorticotropic hormone (ACTH) and cortisol produced by the interrenal cells in the headkidney (adrenal equivalent of fish). CRF is a member of a large family of related peptides that signals through CRF-receptor subtypes specific for central and peripheral actions of the peptide. CRF is "chaperoned" by a unique and phylogenetically very well-conserved binding protein (CRFBP); the functions of the CRFBP can only be speculated on so far, but its mRNA and protein abundance are important indicators of the central CRF-system activity, and indeed its mRNA levels are altered by restraint stress. Moreover, the unique structure and size of the CRFBP provide good tools in phylogenetic studies, that date the CRF-system to at least one billion years old. Pro-opiomelanocortin is produced and processed to ACTH and endorphin in the hypothalamic NPO and pituitary pars distalis ACTH-cells, to MSH and acetylated endorphins in the pituitary pars intermedia MSH-cells. ACTH is the prime corticotrope in acute stress conditions. In carp, MSH, considered a mild corticotrope in chronic stress responses in other fish, lacks corticotropic effects (in line with the absence of the melanocortin-5 receptor in headkidney); yet, an unknown corticotropic signal substance in the pars intermedia of carp awaits elucidation. Interesting observations were made on the CRF control of pituitary cells. CRF stimulates ACTH-cells, but only when these cells experience a mild dopaminergic block. Endorphin, produced in the NPO and transported via axons to the pituitary gland in vivo, reverses the stimulatory CRF action on MSH-cells to a differential inhibition of N-acetyl beta-endorphin release in vitro (MSH release is not affected). We speculate that the consistently observed elevation of plasma MSH during chronic stress may exert central actions related to feeding and leptin regulated processes. A BOLD-fMRI study revealed the functional anatomy of the stress response at work in a paradigm, where carp were exposed to a sudden water temperature drop. In carp (and other fish), the endocrine stress axis is already operational in very early life stages, viz., around hatching and comprises hypothalamic, pituitary, and interrenal signaling to adjust the physiology of the hatchling to its dynamically changing environment. Understanding of stress during early life stages is critical as the consequent rises in cortisol may have long lasting effects on survival and fish quality.

Heads or tails? Stressor-specific expression of corticotropin-releasing factor and urotensin I in the preoptic area and caudal neurosecretory system of rainbow trout

“…In keeping with the proposed function of POA CRF as a key player in the regulation of the HPI axis and the endocrine stress response in fish (Flik et al 2006), all four stressors elicited an increase in POA CRF mRNA expression. Interestingly, however, the magnitude and duration of the increase in POA CRF expression did not correlate with the magnitude and duration of the stress-induced HPI axis response.…”

“…The CRF and UI in teleosts are implicated in the regulation of the neuroendocrine, autonomic, and behavioral responses to stressors (Lovejoy & Balment 1999, Flik et al 2006). While it is not known whether UI-producing neurons directly innervate the pituitary like the CRF-producing neurons of the POA (Matz & Hofeldt 1999, Zupanc et al 1999, both UI and CRF are potent in vitro stimulants of adrenocorticotropic hormone (ACTH; Fryer et al 1983), melanocyte-stimulating hormone (Tran et al 1990), and thyrotrophin (Larsen et al 1998) secretion from fish pituitary cells.…”

Chronic social stress in rainbow trout: Does it promote physiological habituation?

“…Most studies dealing with this subject were conducted on primates and small laboratory mammals and in acute conditions, e.g., when animals are kept above stressor stimuli for a short period of time and the behavioural and physiological responses are monitored during and shortly after the stressor had been removed (Chrousos et al, 1995;Csermely, 1998). In fish, some studies have been carried out using the same procedure and the results obtained were similar to those found for other vertebrates, with activation of the pituitary-4 adrenal (PA) and sympathomedulloadrenal (SMA) axes (Flik et al, 2006; Wendelaar Bonga, 1997). …”

<b>Psychological Stress and Welfare in Fish</b>

“…This includes a number of related peptides also involved in the HPI regulation and expressed in a number of important central and peripheral tissues. Even though CRH's mechanisms of action are still not entirely understood, its control upon adrenocorticotrophic hormone (ACTH) release is well established Flik et al, 2006). In turn, a variety of neurotransmitters and cytokines are able to stimulate the synthesis of CRH (Johnson et al, 1992).…”

“…Developmental factors also account for relevant differences to stress vulnerability. Stress responses develop early in life and may have long-lasting effects (Barton, 2002;Flik et al, 2006). Auperin and Geslin (2008) just demonstrated that early exposure to a brief stressor reduced the cortisol response later in life in rainbow trout.…”