Sensitivity to stress-induced reproductive dysfunction is associated with a selective but not a generalized increase in activity of the adrenal axis

Department of Behavioral Neuroscience, Oregon National Primate Research Center, Oregon Health and Science University, Portland, Oregon, USA.
AJP Endocrinology and Metabolism (Impact Factor: 3.79). 10/2010; 300(1):E28-36. DOI: 10.1152/ajpendo.00223.2010
Source: PubMed


Stress-induced reproductive dysfunction is a relatively common cause of infertility in women. In response to everyday life stress, some individuals readily develop reproductive dysfunction (i.e., they are stress sensitive), whereas others are more stress resilient. Female cynomolgus monkeys, when exposed to mild combined psychosocial and metabolic stress (change in social environment + 20% reduced calorie diet), can be categorized as stress sensitive (SS; they rapidly become anovulatory in response to stress), medium stress resilient (MSR; they slowly become anovulatory in response to prolonged stress), or highly stress resilient (HSR; they maintain normal menstrual cycles in response to stress). In this study, we examined whether increased sensitivity to stress-induced reproductive dysfunction is associated with elevated adrenal axis activity by measuring 1) the diurnal release of ACTH and cortisol, 2) ACTH and cortisol in response to an acute psychological stress, 3) the percent suppression of cortisol in response to dexamethasone negative feedback, 4) the diurnal release of ACTH and cortisol following exposure to mild psychosocial and metabolic stress, 5) the concentration of cortisol in hair, and 6) adrenal weight. SS monkeys (n = 5) did not differ from MSR (n = 5) or HSR (n = 7) monkeys in any measurement of baseline HPA axis activity or the integrated measurements of chronic HPA axis activity. However, MSR + SS monkeys (n = 10) did secrete more cortisol than HSR monkeys during the daytime hours (1000-1800) following exposure to a novel social environment and reduced diet. We conclude that increased activity of the HPA axis is unlikely to be the primary mechanism causing increased sensitivity to stress-induced reproductive dysfunction.

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    • "Specifically, after chronic treatment with an SSRI, the stress sensitive monkeys had an increased number of CRF2 receptor mRNA positive cells as found through digoxigenin-in situ hybridization staining, compared to less stress-sensitive monkeys. Similar studies have shown that the stress-sensitive monkeys have an increased cortisol response to serotonin release induced by fenfluramine while showing a blunted prolactin release (Bethea et al., 2005a) and basal increased cortisol release during the day (Herod et al., 2011a,b), suggesting further disruption in normal serotonin systems. Interestingly, these monkeys, along with the altered CRF receptors in response to an SSRI, also have lowered CRF fiber density in the DR with an increased number of UCN 1 cell bodies after SSRI treatment (Weissheimer et al., 2010). "
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    ABSTRACT: Corticotropin-releasing factor (CRF) is a 41-amino acid neuropeptide that is involved in stress-related physiology and behavior, including control of the hypothalamic-pituitary-adrenal (HPA) axis. Members of the CRF family of neuropeptides, including urocortin 1 (UCN 1), UCN 2, and UCN 3, bind to the G protein-coupled receptors, CRF type 1 (CRF1) and CRF2 receptors. In addition, CRF binding protein (CRFBP) binds both CRF and UCN 1 and can modulate their activities. There are multiple mechanisms through which CRF-related peptides may influence emotional behavior, one of which is through altering the activity of brainstem neuromodulatory systems, including serotonergic systems. CRF and CRF-related peptides act within the dorsal raphe nucleus (DR), the major source for serotonin (5-HT) in the brain, to alter the neuronal activity of specific subsets of serotonergic neurons and to influence stress-related behavior. CRF-containing axonal fibers innervate the DR in a topographically organized manner, which may contribute to the ability of CRF to alter the activity of specific subsets of serotonergic neurons. CRF and CRF-related peptides can either increase or decrease serotonergic neuronal firing rates and serotonin release, depending on their concentrations and on the specific CRF receptor subtype(s) involved. This review aims to describe the interactions between CRF-related peptides and serotonergic systems, the consequences for stress-related behavior, and implications for vulnerability to anxiety and affective disorders.
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    • "Recently, keratin glucocorticoid concentrations have been investigated as a biomarker of chronic stress or persistent elevation in glucocorticoid concentrations in a variety of mammals, including Rhesus Macaques (Davenport et al., 2006; Dettmer et al., 2009), Crab eating Macaques (Herod et al., 2011), Common Marmosets (Clara et al., 2008), Vervet Monkeys (Fairbanks et al., 2011; Laudenslager et al., 2011), Domestic Dogs (Accorsi et al., 2008; Bennett and Hayssen, 2010), Domestic Cats (Accorsi et al., 2008; Finkler and Terkel, 2010), Eastern Chipmunks (Martin and Reale, 2008), Rock Hyrax (Koren et al., 2002), Caribou and Reindeer (Ashley et al., 2011), Grizzly Bears (Macbeth et al., 2010) and Polar Bears (Bechshoft et al., 2011), as well as birds (Bortolotti et al., 2008, 2009; Harms et al., 2010). Snakes possess a distinct cycle of ecdysis, in which episodic loss (or shedding) of a keratinized old outer epidermal generation occurs following formation of a new keratinized inner epidermal generation . "
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    ABSTRACT: This study investigates the use of an enzyme immunoassay to measure keratin glucocorticoid concentrations in reptilian shed skins. Keratin glucocorticoid concentrations were compared to fecal glucocorticoid concentrations during the period of keratin growth in the African House Snake (Lamprophis fuliginosus) and the Eastern Massasauga Rattlesnake (Sistrurus catenatus catenatus). Biochemical validation was performed for the shed skin and fecal corticosterone enzyme immunoassays in the African House Snake. Biological and physiological validations were attempted in the African House Snake. A statistically significant positive association was detected between shed skin corticosterone and the mean fecal corticosterone metabolites from 3 weeks before to 1 week after the previous ecdysis in the African House Snake. A statistically significant difference was not detected between the shed skin corticosterone concentrations of the minimally handled control and the weekly handled (or experimentally stressed) African House Snakes. Adrenocorticotropic hormone stimulation did not result in the physiological validation anticipated for shed skin corticosterone concentrations in the African House Snake.
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