Variations in the Hypothalamic-Pituitary-Adrenal Response to Stress during the Estrous Cycle in the Rat

Abstract

ABSTRACfTo investigate the role of gonadal steroids in the hypothalamic-pituitary-adrenal (HPA) response to stress, we studied adrenocorticotrophin (ACIlI) and corticosterone (B) responses to 20 min re~traint stress in cycling female rats, and in ovariectomized (OVX) rats replaced with physiologicallevels of estradiol (E2) and progestefCIne (P). In cycling rats, we found significantly iligher peak ACfH (p < 0.01) and B (p < 0.05) responses to stress during proestrous compared to the estrous and diestrous phases. No differences were found in either basal ACIH and B levels across the cycle phases. In a seperate study, OVX rats were rnaintained on low, physiologicallevels ofE2 and P with silas tic implants for three days, and injected either with oil (0'), 10 ug of E2 (E') 24 h befon' stress testing, or with E2 and 500 ug P 24 h and 4 h, respectively, prior to stress (EP'). These treatments mimicked endogenous profiles of E2 and P occurine during diestrous, proestrous, and late proestrous-early estrous phases, respectively. In response to stress, ACfH levels were higher (p < 0.01) in the E' group compared to the EP' and 0' groups. Although the peak B response was similar in aIl groups, the E' and EP' groups secreted more B following the termination of stress than did the 0' group. Within the 20 min stress period, ACfH levels in the E' group were significantly (p < 0.05) higher at 5, 10, and 15 min after the onser of stress, compared to the EP' and 0' groups. Plasma B levels were significantly higher in the E' group at 5 and 10 min (p < 0.05 and p < 0.01, respectively) compared to the EP' and 0' group. B-endorphin-like immunoreactive responses to restraint stress were aiso significanùy higher in the E' group compared to the EP' (p < 0.05) and 0' (p < 0.01) groups. There was no effect of E2 on ACfH clearance. These results indicate that the HPA axis in the femate rat is most 11 sensitive to stress during proestrous. Such enhanced HPA responses to stre~,s are limitcd to the early portion of proestrous, as progesterone appears to inhibit the tacilitatory effects of estrogen on ACTH release during stress. Taken together. these results suggest an ovarian influence on both activatonal and inhibitory components of HPA activity.Nous avons investi gué le rôle des stéroides ovariens dans la réponse de l'axe hypothalamo-hypophyso-surrénalien (HPA) aux stress. Pour ceci, la réponse de

Effects of Estrogen Antagonists and Agonists on the ACTH Response to Restraint Stress in Female Rats

“…The findings in our study contrast with several previous reports of increased HPA axis responses to stress after estradiol treatment (Burgess and Handa 1992;Carey et al 1995;Viau and Meaney 1991). A major difference between our study and these prior reports is that the dosage of estradiol was much higher in these earlier studies.…”

“…A major difference between our study and these prior reports is that the dosage of estradiol was much higher in these earlier studies. Viau and Meaney (1991) examined the effects of a single dose of 10 g of estradiol, which is five-fold higher than our dose. The plasma levels of estradiol achieved with that dose were 535 pg/ml, or five times proestrous levels.…”

“…Compared with male rats, female rats also have a greater ACTH response to stress, faster onset of corticosterone secretion after stress, and a faster rate of rise of corticosterone (Le Mevel et al 1979;Jones et al 1972;Young 1996). Several studies suggest that estradiol plays a role in enhanced stress responses in female rats, based on increased HPA axis responses to stress when ovariectomized rats are treated with estradiol (Burgess and Handa 1992;Carey et al 1995;Viau and Meaney 1991). In addition, female rats have enhanced HPA axis responsivity in proestrus, when estrogen and progesterone levels are relatively high, compared to diestrus, when levels of these hormones are lower (Viau and Meaney 1991).…”

Vasopressin Mediates the Response of the Combined Dexamethasone/CRH Test in Hyper-anxious Rats Implications for Pathogenesis of Affective Disorders

“…It has been reported that the activity of the HPA system varies with the level of sexual steroids during the estrous cycle (Viau and Meaney 1991) and during female reproduction (Lightman and Young 1989;Walker 1995;Neumann et al 1998a,b), and that there are differences between males and females (Kitay 1961;Rivier 1999;Neumann et al 2000). Interestingly, prenatal (Weinstock 1997) and postnatal stress altered HPA system responsiveness in adult male, but not female, offspring demonstrating a greater vulnerability in males than in females.…”

Sex steroid modulation of cortisol secretion in sheep

“…The stress response of the HPA axis of female rats is greater than that of male rats and gonadal steroid levels are in part responsible for these differences (Handa et al, 1994). This has been observed both under basal and stressful conditions in rats (Kitay, 1961;Viau and Meaney, 1991) and in primates (Uhart et al, 2006). Oestrogens enhance ACTH secretion and testicular androgens suppress corticosterone secretion in the † E-mail: evanlier@fagro.edu.uy Animal (2014) Burgess and Handa, 1992;Young, 1995;Viau and Meaney, 1996).…”