Female temperament, tumor development and life span: Relation to glucocorticoid and tumor necrosis factor α levels in rats

Abstract

Behavioral characteristics closely associated with specific physiological profiles present an important area of research in understanding health disparities. In particular, glucocorticoid overproduction may be an important factor moderating disease progression; natural variance in production of this steroid has been proposed as one mechanism underlying individual differences in health and disease. In the current paper, we examined immune parameters in female rats of two different behavioral types previously shown to have differential glucocorticoid production and life spans. We categorized young female rats according to their behavioral response to novelty (high-or low-locomotion), and compared their glucocorticoid production, adrenal size, thymus size, tumor necrosis factor-α (TNF-α) production, tumor development and life span. As expected, high-locomotion females produced more glucocorticoids and had larger adrenal glands during young adulthood than did low-locomotion females. High-locomotion females had significantly smaller thymuses and reduced TNF-α levels compared to low-locomotion, suggesting altered immune function in young adulthood. Finally, highlocomotion females had shorter life spans than did low-locomotion females, and this was particularly true in females that developed pituitary tumors, but not in those that developed mammary tumors. These results, along with other published findings, suggest that high-locomotion rodent females experience life-long elevations in glucocorticoid responses to novelty, and that these elevated levels may be comparable to chronic stress. This naturally-occurring endocrine profile may influence immune responses which in turn could affect disease susceptibility. Variance in immune function across personality types may be partially moderated by natural variance in glucocorticoid production.

Individual differences in pre-carcinogen cytokine and corticosterone concentrations and depressive-like behavior predict tumor onset in rats exposed to a carcinogen

“…The observed relationship between low resting corticosterone concentrations and early cancer onset is consistent with previous research demonstrating that lower HPA axis responses to stressors or lower baseline corticosterone concentrations may predict tumor development (Strange et al, 2000; Cavigelli et al, 2008; Yee et al, 2008). Additionally, rat strains that are characterized by blunted HPA axis responses to stressors, are more susceptible to experimental autoimmune encephalomyelitis (EAE) (Gasser et al, 1973) and arthritis than strains that are not (Sternberg et al, 1989; but see Chover-Gonzalez et al, 2000).…”

“…Relatively high rat neophobic behavior in infancy is also associated with earlier spontaneous mammary tumors and death compared with that of less neophobic siblings (Cavigelli et al, 2006). Blunted corticosterone responses to a stressor are observed in neophobic rats in the absence of coincidentally elevated TNFα responses (Cavigelli et al, 2008). In contrast, elevated HPA axis responses to a stressor coincided with low learned helplessness behavior and subsequently exacerbated adjuvant arthritic inflammation (Chover-Gonzalez et al, 2000).…”

Behavioral responses to physical vs. social novelty in male and female laboratory rats

“…Dissociation of behavioral responses to social vs. physical stimuli has been identified only recently and in limited studies (e.g., Bielsky et al, 2004; Cavigelli et al, 2007 & 2008; Coleman and Wilson, 1998; Egashira et al, 2007; Liu and Smith, 2009; Prather et al, 2001). Several studies have specifically measured mouse ‘sociability’ across strains to develop models of human autism and comparable to the current rat study, nearly all mice strains spent more time sniffing a cage containing another mouse than an empty cage (Moy et al, 2007 & 2008; Sankoorikal et al, 2006).…”

Marine Collagen Peptides Prepared from Chum Salmon (Oncorhynchus keta) Skin Extend the Life Span and Inhibit Spontaneous Tumor Incidence in Sprague-Dawley Rats

“…26 The date of each death was recorded, and the mean overall life span, the mean life span of the last 30% of the animals, and the maximal life span were evaluated.…”