Trends of Reproductive Hormones in Male Rats During Psychosocial Stress: Role of Glucocorticoid Metabolism in Behavioral Dominance1

Abstract

Stress in socially subordinate male rats, associated with aggressive attacks by dominant males, was studied in a group-housing context called the visible burrow system (VBS). It has been established that subordinate males have reduced serum testosterone (T) and higher corticosterone (CORT) relative to dominant and singly housed control males. The relationship of the decreased circulating T levels in subordinate males to changes in serum LH concentrations has not been evaluated previously. Since decreases in LH during stress may cause reductions in Leydig cell steroidogenic activity, the present study defined the temporal profiles of serum LH, T, and CORT in dominant and subordinate males on Days 4, 7, and 14 of a 14-day housing period in the VBS. The same parameters were followed in serum samples from single-housed control males. Leydig cells express glucocorticoid receptors and may also be targeted for direct inhibition of steroidogenesis by glucocorticoid. We hypothesize that Leydig cells are protected from inhibition by CORT at basal concentrations through oxidative inactivation of glucocorticoid by 11beta-hydroxysteroid dehydrogenase (11betaHSD). However, Leydig cell steroidogenesis is inhibited when 11betaHSD metabolizing capacity is exceeded. Therefore, 11betaHSD enzyme activity levels were measured in Leydig cells of VBS-housed males at the same time points. Significant increases in LH and T relative to control were observed in the dominant animals on Day 4, which were associated with the overt establishment of behavioral dominance as evidenced by victorious agonistic encounters. Serum LH and T were lower in subordinate males on Day 7, but T alone was lower on Day 14, suggesting that lowered LH secretion in subordinates may gradually be reversed by declines in androgen-negative feedback. Serum CORT levels were higher in subordinate males compared to control at all three time points. In contrast, oxidative 11betaHSD activity in Leydig cells of dominant males was higher relative to control and unchanged in subordinates. These results suggest the following: 1) failure of Leydig cells of subordinate males to compensate for increased glucocorticoid action during stress, by increasing 11betaHSD oxidative activity, potentiates stress-mediated reductions in T secretion; and 2) an inhibition of the reproductive axis in subordinate males at the level of the pituitary.

Dynamic body weight and body composition changes in response to subordination stress

“…All of these parameters indicate that both DOM and SUB indeed experience stress in the VBS. In addition, SUB animals develop enlarged spleens (possibly attributable to increased wounding) and have decreased testes weights [10,28,29]. Body weight loss among SUB is one of the most consistent consequences of social stress in the VBS [10,27,28,34,35] and this will be discussed in further detail in this manuscript.…”

“…DOM also have slightly elevated basal corticosterone levels, although not to the extent of SUB, and this is likely due to some degree of stress from his efforts to maintain DOM status. SUB have decreased plasma testosterone [10,28,29] and both DOM and SUB animals show thymus involution and adrenal hypertrophy [10,28], compared to the CON further suggesting that elevated glucocorticoids in both social groups have affected peripheral organs as well. All of these parameters indicate that both DOM and SUB indeed experience stress in the VBS.…”

“…More recently, we have used the VBS model to examine the effects of social dominance and subordination on the neuroendocrine systems regulating the stress response, reproduction and energy homeostasis [10,24,[27][28][29]. The housing environment in the VBS closely represents the conditions under which rats would live in the wild and serves to facilitate expression of behavioral and physiological responses that would normally occur in that environment.…”

Rapid mechanisms of glucocorticoid signaling in the Leydig cell☆

“…Sharp increases in glucocorticoid levels accompany exposure to stressors such as restrained [8][9][10][11] and psychosocial interaction with a dominant male [17,18] are associated with the decline of testosterone levels in these animals. Apparently, the classic GRs are involved in these glucocorticoid actions.…”

“…Glucocorticoids act directly on Leydig cells to inhibit testosterone biosynthesis [16,48,49]. Elevations in circulating glucocorticoids during stress including restraint stresses [8][9][10][11] and psychosocial stresses of subordinate rats [17,18] can, therefore, cause suppression in androgen secretion at the level of the testis. Following this view, 11βHSD in Leydig cells normally acts as a protective gatekeeper, maintaining testosterone biosynthesis in the presence of basal glucocorticoid concentrations: testosterone secretion is suppressed only if the oxidative capacity of 11βHSD is exceeded or the dehydrogenase component of the enzyme is inhibited.…”