Hypothalamic-pituitary-adrenal (HPA) function also differs by social status. Subordinates have

higher morning cortisol concentrations than dominants (Shively et al., Apr 15 1997), are hypercortisolemic in adrenocorticotropic hormone (ACTH) challenge tests (Shively, Nov 1 1998) (Kaplan et al., 1986), and are insensitive to glucocorticoid-negative feedback in dexamethasone suppression tests (Kaplan et al., Dec 2010) (Shively et al., Apr 15 1997). Hypercortisolemia has been reported in association SB203580 cell line with social subordination in a number of primate species (Abbott et al., Jan 2003). Cynomolgus monkeys have menstrual cycles similar to those of women in length, sex steroid and gonadotropin variations. The peak progesterone concentration in the luteal phase is used as an index of the quality of ovarian function. High values indicate that ovulation occurred, whereas low values indicate impaired ovulation or an anovulatory cycle. We have characterized luteal phase progesterone concentrations in multiple experiments and found that subordinates have lower mean peak levels than their dominant counterparts (Kaplan et al., Dec 2010, 1985; Adams et al., Dec 1985 and Shively and Clarkson, May 1994). Cycles in which luteal phase progesterone concentrations

are low are also characterized by lower follicular phase estradiol concentrations (Adams et al., Dec 1985). Thus, subordinate Fulvestrant females are estrogen deficient relative to their dominant counterparts. These observations are consistent with those of Cameron

and Bethea in stress sensitive cynomolgus macaques (Bethea et al., Dec 2008). This behavioral and physiological profile indicates that socially subordinate female cynomolgus monkeys in these small laboratory social groups are stressed relative to their dominant counterparts. Acute social defeat is a social stressor used in some rodent and tree shrew stress models of depression. Resminostat While social subordination includes instances of social defeat, it also includes four other features that are likely important to the nature of the stressor: 1) cynomolgus monkeys normally live in social groups which are characterized by stable linear social status hierarchies throughout their lives; 2) these hierarchies are usually established in a matter of hours or days and do not generally involve much overt aggression; 3) while subordinates appear stressed relative to dominants, it is a level of physiological stress to which they can accommodate throughout their lifetime; and 4) time spent being groomed is positively correlated with social status while time spent fearfully scanning is negatively correlated with social status, suggesting that fear and a lack of positive social interaction are as important as hostility received in the experience of social subordination stress.