Gene expression of sex steroid metabolizing enzymes and receptors in the skeletal muscle of migrant and resident subspecies of white-crowned sparrow (Zonotrichia leucophrys).

Circulating sex steroid concentrations vary dramatically across the year in seasonally breeding animals. The ability of circulating sex steroids to effect muscle function can be modulated by changes in intracellular expression of steroid metabolizing enzymes (e.g., 5α-reductase type 2 and aromatase) and receptors. Together, these combined changes in plasma hormones, metabolizing enzymes and receptors allow for seasonally appropriate changes in skeletal muscle function. We tested the hypothesis that gene expression of sex steroid metabolizing enzymes and receptors would vary seasonally in skeletal muscle and these changes would differ between a migrant and resident life history strategy. We quantified annual changes in plasma testosterone and gene expression in pectoralis and gastrocnemius skeletal muscles using quantitative polymerase chain reaction (qPCR) in free-living migrant (Zonotrichia leucophrys gambelii) and resident (Z. l. nuttalli) subspecies of white-crowned sparrow during breeding, pre-basic molt, and wintering life history stages. Pectoralis muscle profile was largest in migrants during breeding, while residents maintained large muscle profiles year-round. Circulating testosterone peaked during breeding in both subspecies. Pectoralis muscle androgen receptor mRNA expression was lower in females of both subspecies during breeding. Estrogen receptor-α expression was higher in the pectoralis muscle, but not gastrocnemius, of residents throughout the annual cycle when compared to migrants. Pectoralis aromatase expression was higher in resident males compared to migrant males. No differences were observed for 5α-reductase 2. Between these two subspecies, patterns of plasma testosterone and androgen receptors appear to be conserved, however estrogen receptor gene expression appears to have diverged.

Annual regulation of adrenocortical function in migrant and resident subspecies of white-crowned sparrow.

Corticosterone affects physiology and behavior both during normal daily processes but also in response to environmental challenges and is known to mediate life history trade-offs. Many studies have investigated patterns of corticosterone production at targeted times of year, while ignoring underlying annual profiles. We aimed to understand the annual regulation of hypothalamic-pituitary-adrenal (HPA) axis function of both migrant (Zonotrichia leucophrys gambelii; n = 926) and resident (Z. l. nutalli; n = 688) subspecies of white-crowned sparrow and how it is influenced by environmental conditions - wind, precipitation, and temperature. We predicted that more dramatic seasonal changes in baseline and stress-induced corticosterone would occur in migrants to precisely time the onset of breeding and cope with environmental extremes on their arctic breeding grounds, while changes in residents would be muted as they experience a more forgiving breeding schedule and comparatively benign environmental conditions in coastal California. During the course of a year, the harshest conditions were experienced the summer breeding grounds for migrants, at which point they had higher corticosterone levels compared to residents. For residents, the winter months coincided with harshest conditions at which point they had higher corticosterone levels than migrants. For both subspecies, corticosterone tended to rise as environmental conditions became colder and windier. We found that the annual maxima in stress-induced corticosterone occurred prior to egg lay for all birds except resident females. Migrants had much higher baseline and acute stress-induced corticosterone during breeding compared to residents; where in a harsher environment the timing of the onset of reproduction is more critical because the breeding season is shorter. Interestingly, molt was the only stage within the annual cycle in which subspecies differences were absent suggesting that a requisite reduction in corticosterone may have to be met for feather growth. These data suggest that modulation of the HPA axis is largely driven by environmental factors, social cues, and their potential interactions with a genetic program.

Acute restraint stress does not alter corticosteroid receptors or 11ß-hydroxysteroid dehydrogenase gene expression at hypothalamic-pituitary-adrenal axis regulatory sites in captive male white-crowned sparrows (Zonotrichia leucophrys gambelii).

Capture-restraint is often used to investigate the acute hypothalamic-pituitary-adrenal axis (HPA) response to stress in wild and captive animals through the production of glucocorticoids. Although this approach is useful for understanding changes in glucocorticoids, it overlooks potential changes in the complex regulatory systems associated with the glucocorticoid response, including genomic receptors, steroid metabolizing enzymes, carrier proteins, and downstream target proteins (e.g. gonadotropin-inhibitory hormone; GnIH). The present study in captive male white-crowned sparrows (Zonotrichia leucophrys) tests the hypothesis that corticosteroid receptors (mineralocorticoid - MR and glucocorticoid - GR), 11ß-hydroxysteroid dehydrogenase 1 (11ßHSD1) and 2 (11ßHSD2), corticosteroid binding globulin (CBG), and GnIH undergo rapid changes in expression to mediate the glucocorticoid response to acute stress. To determine dynamic changes in gene mRNA expression in the hippocampus, hypothalamus, pituitary gland, and liver, birds were sampled within 3 min of entering the room and after 10, 30, and 60 min of capture restraint stress in a cloth bag. Restraint stress handling increased CBG and decreased GnIH mRNA expression in the liver and hypothalamus, respectively. MR, GR, 11ßHSD1, and 11ßHSD2 mRNA expression in the brain, pituitary gland, and liver did not change. No correlations were found between gene expression and baseline or stress-induced plasma corticosterone levels. No rapid changes of MR, GR, 11ßHSD1, and 11ßHSD2 mRNA expression during a standardized acute restraint protocol suggests that tissue level sensitivity may remain constant during acute stressors. However, the observed rise in CBG mRNA expression could act to facilitate transport to target tissues or buffer the rise in circulating glucocorticoids. Further studies on tissue specific sensitivity are warranted.

Tissue-specific expression of 11ß-HSD and its effects on plasma corticosterone during the stress response.

The hypothalamic-pituitary-adrenal (HPA) axis is under complex regulatory control at multiple levels. Enzymatic regulation plays an important role in both circulating levels of glucocorticoids and target tissue exposure. Three key enzyme pathways are responsible for the immediate control of glucocorticoids. De novo synthesis of glucocorticoid from cholesterol involves a multistep enzymatic cascade. This cascade terminates with 11ß-hydroxylase, responsible for the final conversion of 11-deoxy precursors into active glucocorticoids. Additionally, 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) controls regeneration of glucocorticoids from inactive metabolites, providing a secondary source of active glucocorticoids. Localized inactivation of glucocorticoids is under the control of Type 2 11ß-HSD (11ß-HSD2). The function of these enzymes is largely unexplored in wild species, particularly songbirds. Here, we investigated the contribution of both clearance and generation of glucocorticoids to regulation of the hormonal stress response via the use of pharmacological antagonists. Additionally, we mapped 11ß-HSD gene expression. We found 11ß-HSD1 primarily in liver, kidney and adrenal glands, although it was detectable across all tissue types. 11ß-HSD2 was predominately expressed in the adrenal glands and kidney with moderate gonadal and liver expression. Inhibition of glucocorticoid generation by metyrapone was found to decrease levels peripherally, while both peripheral and central administration of the 11ß-HSD2 inhibitor DETC resulted in elevated concentrations of corticosterone. These data suggest that during the stress response, peripheral antagonism of the 11ß-HSD system has a greater impact on circulating glucocorticoid levels than central control. Further studies should aim to elucidate the respective roles of the 11ß-HSD and 11ß-hydroxylase enzymes.

Effects of internal and external corporate social responsibility on employee job satisfaction during a pandemic: A medical device industry perspective.

The outbreak of the COVID-19 pandemic has dramatically changed human lifestyles and contributed to the creation of a new normal in the business environment. This study examines the direct and indirect impacts of internal and external corporate social responsibility (CSR) practices on employee job satisfaction through organisational identification, conditional on employee age. A total of 236 valid responses were received from eight multinational medical device manufacturers in Malaysia. Partial least squares and PROCESS algorithms were employed to assess the hypothesised interactions between the predictors and criterion variables. The empirical results showed that internal CSR (i.e., CSR to employee) could significantly drive a greater sense of belonging and work satisfaction. Surprisingly, however, external CSR (i.e., CSR to community) negatively affects job fulfilment in the medical devices industry during the pandemic. Nevertheless, the findings also showed that ongoing CSR activities in the community could build organisational identification and subsequently improve job satisfaction. Conversely, CSR to environment did not statistically influence job satisfaction, either directly or indirectly. The mediating effects of organisational identification were not associated with employee age. This study provides a practical framework for effective CSR strategies amid the pandemic that can help organisations align with social responsibility, enhance their reputation, and contribute to society.