Corticosterone Levels In Females Research Articles

The Level of Sex Hormones and Corticosterone in Female Rats during Modeling of Visceral Obesity, Subsequent Physical Activity, and Normalization of the Diet.

The effects of diet-induced visceral obesity and non-drug options of its correction on the level of sex hormones and corticosterone were evaluated in 84 female Wistar rats. During stage I, the rats received either a standard diet (STD) or a high-calorie diet (HCD) for 8 weeks. During stage II, the animals were divided into subgroups depending on obesity correction: without correction (STD control and HCD), transition from HCD to STD (HCD/STD) and/or physical activity (treadmill exercise) for the next 8 weeks (HCD/STD+exercise, STD+exercise, and HCD+exercise). Diet-induced visceral obesity resulted in hyperandrogenization and increased blood corticosterone levels in females. Transition from HCD to STD regardless of physical activity led to normalization of testosterone level and, accordingly, to return to the functional norm of estrogen-androgen balance. The positive effect of moderate physical activity on hormonal status is realized only against the background of a balanced diet or during the transition from HCD to STD.

Corticosteroid-Binding Globulin (SERPINA6) Consolidates Sexual Dimorphism of Adult Rat Liver.

Produced by the liver, corticosteroid-binding globulin (CBG) regulates the plasma distribution and actions of glucocorticoids. A sex difference in pituitary growth hormone secretion patterns established during puberty in rats results in increased hepatic CBG production and 2-fold higher plasma corticosterone levels in females. Glucocorticoids control hepatic development and metabolic activities, and we have therefore examined how disrupting the SerpinA6 gene encoding CBG influences plasma corticosterone dynamics, as well as liver gene expression in male and female rats before and after puberty. Comparisons of corticosterone plasma clearance and hepatic uptake in adult rats, with or without CBG, indicated that CBG limits corticosterone clearance by reducing its hepatic uptake. Hepatic transcriptomic profiling revealed minor sex differences (207 differentially expressed genes) and minimal effect of CBG deficiency in 30-day-old rats before puberty. While liver transcriptomes in 60-day-old males lacking CBG remained essentially unchanged, 2710 genes were differentially expressed in wild-type female vs male livers at this age. Importantly, ∼10% of these genes lost their sexually dimorphic expression in adult females lacking CBG, including those related to cholesterol biosynthesis, inflammation, and lipid and amino acid catabolism. Another 203 genes were altered by the loss of CBG specifically in adult females, including those related to xenobiotic metabolism, circadian rhythm, and gluconeogenesis. Our findings reveal that CBG consolidates the sexual dimorphism of the rat liver initiated by sex differences in growth hormone secretion patterns and provide insight into how CBG deficiencies are linked to glucocorticoid-dependent diseases.

Multigenerational nicotine exposure affects offspring nicotine metabolism, nicotine-induced hypothermia, and basal corticosterone in a sex-dependent manner

Parental nicotine exposure can impact phenotypes in unexposed offspring. Our laboratory recently published data showing that nicotine reward and hippocampal gene expression involved in stress pathways were perturbed in F1 offspring of male C57BL/6J mice chronically exposed to nicotine. For the current study, we aimed to further test nicotine and stress-sensitivity phenotypes that may predict vulnerability to nicotine addiction in new cohorts of F1 offspring derived from nicotine-exposed males. We tested locomotor and body temperature sensitivity to acute nicotine administration, serum concentration of nicotine and nicotine metabolites after acute nicotine dosing, and serum corticosterone levels in male and female F1 offspring of nicotine- or saline-exposed males. Paternal nicotine exposure reduced sensitivity to nicotine-induced hypothermia in males, altered nicotine metabolite concentrations in males and females, and reduced serum basal corticosterone levels in females. These findings may point to reduced susceptibility to nicotine addiction-related phenotypes as a result of parental nicotine exposure.

Glucocorticoid levels are linked to lifetime reproductive success and survival of adult barn owls.

Glucocorticoid hormones, such as corticosterone, are crucial in regulating daily life metabolism and energy expenditure, as well as promoting short-term physiological and behavioural responses to unpredictable environmental challenges. Therefore, glucocorticoids are considered to mediate trade-offs between survival and reproduction. Relatively little is known about how selection has shaped glucocorticoid levels. We used 15years of capture-recapture and dead recovery data combined with 13years of corticosterone and breeding success data taken on breeding barn owls (Tyto alba) to investigate such trade-offs. We found that survival was positively correlated with stress-induced corticosterone levels in both sexes, whereas annual and lifetime reproductive success (i.e. the sum of young successfully fledged during the entire reproductive career) was positively correlated with both baseline and stress-induced corticosterone levels in females only. Our results suggest that, in the barn owl, the stress-induced corticosterone response is a good proxy for adult survival and lifetime reproductive success. However, selection pressure appears to act differently on corticosterone levels of males and females.

Developmental programming of the adrenocortical stress response by yolk testosterone depends on sex and life history stage.

Developmental exposure of embryos to maternal hormones such as testosterone in the avian egg influences the expression of multiple traits, with certain effects being sex specific and lasting into adulthood. This pleiotropy, sex dependency and persistency may be the consequence of developmental programming of basic systemic processes such as adrenocortical activity or metabolic rate. We investigated whether experimentally increased in ovo exposure to testosterone influenced hypothalamus-pituitary-adrenal function, i.e. baseline and stress-induced corticosterone secretion, and resting metabolic rate (RMR) of adult male and female house sparrows (Passer domesticus). In previous experiments with this passerine bird we demonstrated effects of embryonic testosterone exposure on adult agonistic and sexual behavior and survival. Here we report that baseline corticosterone levels and the stress secretion profile of corticosterone are modified by in ovo testosterone in a sex-specific and life history stage-dependent manner. Compared with controls, males from testosterone-treated eggs had higher baseline corticosterone levels, whereas females from testosterone-treated eggs showed prolonged stress-induced corticosterone secretion during the reproductive but not the non-reproductive phase. Adult RMR was unaffected by in ovo testosterone treatment but correlated with integrated corticosterone stress secretion levels. We conclude that exposure of the embryo to testosterone programs the hypothalamus-pituitary-adrenal axis in a sex-specific manner that in females depends, in expression, on reproductive state. The modified baseline corticosterone levels in males and stress-induced corticosterone levels in females may explain some of the long-lasting effects of maternal testosterone in the egg on behavior and could be linked to previously observed reduced mortality of testosterone-treated females.

Cross-Generational Transmission of Early Life Stress Effects on HPA Regulators and Bdnf Are Mediated by Sex, Lineage, and Upbringing

Early life stress (ELS) is a potent developmental disruptor and increases the risk for psychopathology. Various forms of ELS have been studied in both humans and rodents, and have been implicated in altered DNA methylation, gene transcription, stress hormone levels, and behavior. Although recent studies have focused on stress-induced epigenetic changes, the extent to which ELS alters HPA axis function and stress responsivity across generations, whether these effects are sex-specific, and how lineage interacts with upbringing to impact these effects, remain unclear. To address these points, two generations of rodents were utilized, with the first generation subjected to ELS via maternal separation, and the second to a balanced cross-fostering paradigm. We hypothesized that ELS would disrupt normative development in both generations, manifesting as altered methylation and expression of genes associated with stress signaling pathways (Nr3c1, Nr3c2, and Bdnf), blunted corticosterone (CORT), and anxiety-like behaviors. Additionally, we expected deficits in the second generation to be modulated by caretaking environment and for the pattern of results to differ between the sexes. Results suggest that direct exposure to ELS leads to sex-specific effects on gene regulation and HPA functioning in adulthood, with maternal separation leading to increases in Bdnf methylation in both sexes, decreases in Bdnf expression in females, and decreases in Nr3c1 methylation in males, as well as blunted CORT and less anxiety-like behavior in females. These alterations converged with caretaking to impart perturbations upon the subsequent generation. Across sex, ELS lineage led to decreased methylation of Nr3c1, and increased methylation of Bdnf. In fostered animals, upbringing by a previously stressed mother interacted with offspring lineage to impact methylation of Nr3c1 and Bdnf. Upbringing was also implicated in altered anxiety-like behavior in males, and baseline CORT levels in females. Such effects may correspond with observed alterations in maternal behavior across groups. In conclusion, ELS conferred enduring sex-specific alterations, both first-hand and trans-generationally via lineage and upbringing. Importantly, lineage of cross-fostered pups was sufficient to normalize or disturb maternal behavior of foster-dams, an observation requiring further elucidation. These results have implications for multi-generational effects of ELS in humans and may motivate early interventions.

The effects of neonatal paternal deprivation on pair bonding, NAcc dopamine receptor mRNA expression and serum corticosterone in mandarin voles

High levels of paternal care are important for the development of social behavior in monogamous rodents. However, the effects of paternal care on the formation of pair bonding and underlying neuroendocrine mechanisms, especially the involvements of dopamine system and corticosterone, are not well understood. We investigated effects of paternal deprivation on pair bonding in mandarin voles (Microtus mandarinus), a socially monogamous rodent. Paternal deprivation was found to inhibit the formation of pair bonding in females according to partner preference tests (PPT). Paternal deprivation also reduced body contact behavior and increased aggression in males and females in PPT. During social interaction tests (SIT), paternal deprivation was found to reduce investigative and aggressive behaviors but increase body contact and self-grooming in females, and reduce staring, aggression, body contact and self-grooming in males when interacting with the opposite sex. Paternal deprivation reduced the expression of dopamine 1-type receptor (D1R) mRNA and dopamine 2-type receptor (D2R) mRNA in the nucleus accumbens of female offspring in later life, but enhanced mRNA expression of these two dopamine receptors in males. After three days of cohabitation the expression of D1R mRNA and D2R mRNA was negatively correlated for voles reared by two parents, but positively correlated in paternally deprived animals. Paternal deprivation reduced serum corticosterone levels in females but had the opposite effect in males. Three days of cohabitation did not alter corticosterone levels of PD females, but reduced it in PC females. Our results provide substantial evidence that paternal deprivation inhibits the formation of pair bonding in female mandarin voles and alters social behavior later in life. These behavioral variations were possibly associated with sex-specific alterations in the expression of two types of dopamine receptors and serum corticosterone levels induced by paternal deprivation.

State dependent effects of elevated hormone: Nest site quality, corticosterone levels and reproductive performance in the common eider

Nest shelter in incubating birds is of major importance in providing protection against unfavourable conditions such as harshness of the environment and exposure to predators. We examined the link between nest shelter, baseline corticosterone (CORT) levels and hatching success in common eiders ( Somateria mollissima) incubating at nest sites with different levels of shelter. Since more sheltered nest sites could be occupied by better-quality females, we also used an experimental manipulation of nest shelter to separate the effects of the physical attributes of the nest site from those of individual quality. We compared birds with naturally sheltered nests, exposed nests and exposed nests provided with artificial nest shelters and measured clutch size, body condition, CORT levels at the end of incubation and hatching success. If nest shelter reduces CORT levels, we predicted that CORT levels would be highest at the least sheltered sites, and that the provision of artificial shelter would reduce CORT levels. We found that nest shelter was not related to CORT levels in incubating eiders. Nest shelter, however, affected body condition, with females at exposed sites losing more body mass during incubation than females at naturally and artificially sheltered nests. Interestingly however, in those birds nesting at the exposed sites, with and without artificial shelter, those with the highest CORT levels had the lowest hatching success. This relationship was not evident in females nesting at naturally sheltered sites. These results suggest that the level of nest shelter does not directly affect CORT levels in females. Instead, we suggest that the relationship between CORT levels and hatching success is state-dependent. Exposed sites are occupied by individuals that laid smaller clutches, and hence are likely to be of lower quality, and the negative effects of elevated CORT on hatching success are more pronounced in these females.

Corticosterone stress response and plasma metabolite levels during breeding and molt in a free-living migratory songbird, the wood thrush ( Hylocichla mustelina)

Many birds face energetic trade-offs between different life history stages, such as reproductive effort, feather molt and the non-breeding period. Little is known about how physiological measures of condition (corticosterone, plasma metabolites) in free-living birds change from nesting stages to the post-breeding molt period or whether this is influenced by prior reproductive effort. We evaluated whether corticosterone (CORT) and plasma metabolite levels vary with date, nest stage and sex in a free-living migratory songbird, the wood thrush ( Hylocichla mustelina). We also tested whether (1) baseline CORT levels early in the season were predictive of subsequent reproductive success and (2) whether prior reproductive effort influenced CORT levels and blood metabolites during molt. Baseline CORT levels decreased with date during both the incubation stage and nestling stage, but did not vary significantly across stage of breeding season. Stress-induced CORT declined with date during incubation and varied significantly across breeding stage, with lower levels during feather molt. Profiles of the metabolites of β-hydroxybutyrate, glycerol, and triglyceride did not vary significantly with date or breeding stage. Only triglycerides varied significantly with sex, with females having higher levels than males. Reproductive output was highly variable (0–10 fledglings per season) but baseline CORT levels in females during the first incubation period of the season was not related to subsequent reproductive output. Prior reproductive effort, measured as the cumulative number of young hatched during the breeding season, was positively related to stress-induced CORT during molt. High reproductive effort in wood thrush appears to have physiological carry-over effects into the molt period which could potentially affect rate of molt and preparation for fall migration.

Effects of maternal corticosterone and stress on behavioral and hormonal indices of formalin pain in male and female offspring of different ages

In previous studies, we showed for the first time that prenatal stress in rats produces long-term alterations of formalin-induced pain behavior that are dependent on age and sex, and we demonstrated an important role of the serotonergic system in mechanisms of prenatal stress (Butkevich, I.P. and Vershinina, E.A., 2001; Butkevich, I.P. and Vershinina, E.A., 2003; Butkevich, I.P., Mikhailenko, V.A., Vershinina, E.A., Khozhai, L.I., Grigorev, I.P., Otellin, V.A., 2005; Butkevich, I.P., Mikhailenko, V.A., Khozhai, L.I., Otellin, V.A., 2006). In the present study, we focus on the influence of the maternal corticosterone milieu and its role in the effects of stress during pregnancy on formalin-induced pain and the corticosterone response to it in male and female offspring of different ages. For this purpose, we used adrenalectomy (AD) in female rats 3–4 weeks before mating (as distinct from AD typically performed at the beginning of pregnancy). Since AD is considered a reliable method to treat hypercortisolism, researches on the effects of long-term AD in dams on the systems responsible for adaptive behavior in offspring are important (such studies are not described in the literature). The results demonstrate that the differences in the corticosterone response to injection of formalin and saline are obvious in 90-day-old (adult) female offspring but masked in 25-day-old ones. AD promoted the corticosterone response to formalin-induced pain but not to injection of saline in prenatally non-stressed female offspring of both ages. Prenatal stress canceled the differences in corticosterone response to injection of formalin and saline in 25-day-old offspring of AD dams and in adult offspring of sham-operated (SH) dams but caused similar differences in adult offspring of AD dams. Sex differences were found in basal corticosterone levels in AD prenatally stressed rats of both age groups, with a higher level in females, and in the corticosterone response to formalin-induced pain in the adult rats of all groups investigated, with higher corticosterone levels in females. In regard to pain behavior, AD induced significant changes in flexing + shaking in prenatally non-stressed adult offspring and canceled the differences in this behavior between non-stressed and stressed 25-day-old offspring. There were sex differences in pain behavior of the adult rats: greater flexing + shaking in AD non-stressed males but in SH non-stressed females; greater licking in prenatally-stressed AD and SH females. These results indicate that the long-term influences of maternal corticosterone on formalin-induced pain and the corticosterone response to it are determined by the sex and age of the offspring and suggest that other mechanisms, including serotonergic ones revealed in our previous studies, are involved in the effects of prenatal stress on inflammatory pain behavior.

Effects of perinatal oxycodone exposure on the response to CRH in late adolescent rats

We hypothesized that prenatal oxycodone exposure suppresses the Hypothalamic–Pituitary–Adrenal (HPA) response to stress in late adolescence. Dark Agouti rats were given either intravenous oxycodone or vehicle (controls, CON) daily from gestation day 8 until postnatal day (PD) 5. At PD 45, the male and female offspring received intravenously either ovine corticotropin releasing hormone (CRH) or saline. Plasma adrenocorticotropic hormone (ACTH) and corticosterone (CORT) levels were determined before, and 15, 30, and 60 min after injection. Prenatal oxycodone had no effect on baseline ACTH values; CRH elicited a greater ACTH response than saline. In males, prenatal oxycodone delayed and enhanced the peak ACTH response to CRH, but had no effect in females. The CORT response to CRH was not different between oxycodone and CON; however mean CORT levels in females were significantly higher than those in males at baseline and after stimulation. These results demonstrate that prenatal oxycodone increases pituitary response to CRH in late adolescent male rats, but not in females. The absence of an enhanced adrenal response in oxycodone-exposed males suggests either desensitization or maximal adrenal response to a high CRH dose. The mechanisms of postnatal sex-specific HPA dysregulation following prenatal oxycodone remain to be elucidated.

Hormone Levels and Infection of Haemoproteus danilewskyi in Free-Ranging Blue Jays (Cyanocitta cristata)

Annual spring relapse of blood parasite infections in birds is believed to be the result of hormonal changes associated with breeding. As part of a larger study on the epizootiology of Haemoproteus danilewskyi in blue jays in south-central Florida, we studied the relationship between H. danilewskyi infections and levels of luteinizing hormone, prolactin, progesterone, testosterone, estradiol, and corticosterone. We found a positive association between intensity of H. danilewskyi infection and corticosterone levels in females but not in males. We also found no association between infection and levels of prolactin, luteinizing hormone, progesterone, testosterone, or estradiol in males or females. In addition, we found a positive relationship between levels of corticosterone and handling time and between corticosterone and testosterone levels. We suggest a possible influence of corticosterone on spring relapse of Haemoproteus spp. infections in birds but provide no support for the influence of breeding hormones on relapse of these parasites.

Reduced levels of thyroid hormones, insulin, and glucose, and lower body core temperature in the growth hormone receptor/binding protein knockout mouse.

The mechanisms that are responsible for the extension of lifespan in the mouse with targeted disruption (knockout [KO]) of the growth hormone (GH) receptor/binding protein (GHR-KO) are unknown. However, in the long-living Ames dwarf mouse, blood glucose and body core temperature (Tco) are consistently lower than in normal mice. In addition, insulin levels are reduced and corticosterone levels are elevated in male dwarfs. These functional alterations, similar to those seen in animals under caloric restriction, have not been proven to be causally related to the extension of lifespan, but they do provide some insight into what traits may be necessary for long life. Therefore, to investigate which of these parameters are similarly affected in two genetically unrelated, yet similarly long-living mouse models, we measured Tco, thyroid hormones (triiodothyronine [T3] and thyroxine [T4]), and insulin, in addition to morning and afternoon levels of glucose and corticosterone, in young adult male and/or female GHR-KO mice and their normal siblings. Tco in GHR-KO mice was numerically reduced throughout the 24-hr period; however, these differences were only significant 4 hr prior to lights-off (14:00 hr), immediately after lights-off (18:00 hr), and during the 3 hr preceding lights on (03:00 to 06:00 hr). GHR-KO mice had significantly reduced levels of T3 and T4, while the ratio of these hormones was similar to that in normal mice. Insulin levels in GHR-KO mice were lower than in normal mice; levels in male GHR-KO mice were below the detectable limits of the assay used. Glucose levels in GHR-KO mice (male and females) were lower than in normal mice in measurements taken in both morning and afternoon; however, these differences arose from consistent reductions in males, as morning glucose levels in GHR-KO females were similar to those of normal mice. Corticosterone levels measured in blood plasma collected under basal (nonstressed) conditions showed sex-related alterations. Basal corticosterone levels in female GHR-KO mice were similar to normal females, while those in male GHR-KO mice were higher than in normal males in the afternoon. Corticosterone levels in stressed GHR-KO females were similar to those measured in stressed normal females. These data show that the long-living GHR-KO mouse shares a reduction in glucose, insulin, thyroid hormones, and Tco with the Ames dwarf mouse. Reductions in these parameters may be important to the underlying mechanisms of delayed aging in these animals.

Prenatal stress in rats: effects on plasma corticosterone, hippocampal glucocorticoid receptors, and maze performance

The present experiments were designed to investigate the effects of maternal stress on cognitive and endocrine parameters in the adult offspring. Pregnant rats were stressed daily during the last week of pregnancy (days 15–19) by restraint, and the performance of their offspring in the Morris water maze was recorded. Plasma corticosterone levels after swimming and the status of hippocampal glucocorticoid receptors (GRs) were determined. During acquisition of the task, prenatally stressed (PS) males — but not females — showed longer escape latencies than non-stressed controls when swimming in cold (10°C) but not in warm (20°C) water. This sex- and prenatal stress-specific difference was even more pronounced during reversal learning of the task. In contrast, PS females — but not males — had higher basal corticosterone levels and a lower density of hippocampal corticosteroid receptors than non-stressed controls. In all animals irrespective of treatment, swimming in the water maze causes an increase of corticosterone that was smaller on day 8 of swimming than on day 1. After swimming in cold water, the rise in corticosterone levels in females was steeper and returned faster to baseline values than after swimming in warm water. A similar pattern could be seen in PS females when compared to their non-stressed controls. The data suggest that prenatal stress impairs spatial learning in males but not in females. Basal and stress-induced increases in corticosterone levels, however, were altered in PS females and not in PS males; i.e., prenatal stress-induced changes in corticosterone secretion were not paralleled by prenatal stress-induced deficits in spatial learning.

Defeat is a major stressor in males while social instability is stressful mainly in females: towards the development of a social stress model in female rats

Social stress models appear useful in elucidating the interrelationship between stress, mood disorders, and drug efficacy. However, reliable social stress models for females are virtually lacking. The aim of this study was to determine stress-related consequences of (a) defeat in aggressive encounters and (b) social instability, in male and female rats. Defeat in male and female subjects was induced by aggressive male residents and female residents made aggressive by surgery (mediobasal hypothalamic lesion [MBHL]), respectively. Aggressiveness of resident males and resident MBHL females was remarkably similar. Alternating isolation and mixed-sex crowding phases with membership rotation were used to induce social instability. Aggression was kept low in the latter paradigm by manipulating crowding group composition. Defeat stress reduced weight gain, and increased both adrenals and plasma corticosterone in males. Only adrenal weight was affected in females. Social instability reduced weight gain, and induced thymus involution, adrenal hypertrophy and elevated plasma corticosterone levels in females. Only weight gain and thymus weights were affected in males. It is concluded that defeat stresses males more than females, while social instability is more stressful for females than for males, if aggressive contacts are low. It is suggested that the social instability model is a good model of social stress in females.

Opioid Peptide Modulation of Stress-Induced Plasma Steroid Changes in the Frog Rana esculenta

The present paper aims to evaluate whether a neuroendocrine system including opioids accounts for the effects of stress in the frog, Rana esculenta. Using an acute-stress paradigm, the involvement of hypothalamic opioid peptides was investigated biochemically as well as by in vivo studies. HPLC and RIA investigations confirm the presence of β-endorphin-like peptides in the brain of this frog. Several immunoreactive peaks are present, two of them coeluting with β-endorphin and acetyl β-endorphin reference peptides. Quantitative evaluation revealed that the β-EP content of 24-hr captured animals was higher than that in fresh captured ones. The stress paradigm, applied here was consistent with the measurement of plasma androgens and corticosterone levels in females after short-captivity confinement. In comparison with fresh-captured animals, a sharp decrease of these levels was found within 10-24 hr after capture. These effects were reversed by naltrexone, a long-acting opioid antagonist, after 24 hr of treatment. In fact, in the captive animals injected with 100 ng of naltrexone, the plasma androgen titers remained low at the 10th hour postcapture, but rose to the control levels within 24 hr. A similar effect was found for the plasma corticosterone levels. These data demonstrate that, in this anuran, endogenous opioids could mediate the stress-induced inhibition of gonadal function, and perhaps the inhibition of the hypothalamus-pituitary-adrenal axis.

Circadian rhythm of circulating corticosterone and prolactin levels in spontaneously hypertensive rats

Circulating levels of corticosterone and prolactin were measured by radioimmunoassay at hourly intervals during a 24 h period to establish the diurnal rhythm of these hormones in spontaneously hypertensive rats (SHR). Corticosterone levels exhibited a distinct circadian variation with concentrations reaching a zenith at 2000 h and a nadir at 1200 h in male and female SHR. Corticosterone levels in females were consistently greater than males. Circulating prolactin levels were greater during the light h than dark in the female; the opposite occurred in males. Measurement of pituitary prolactin content tended to be low when serum prolactin levels were high and vice versa. The circadian rhythm of circulating corticosterone and prolactin in the hypertensive SHR was found to be similar to the day-night patterns established for normotensive rats. However, these measurements were made under quiescent conditions. It is suggested that because SHR are hyper-responsive to stress and because corticosterone and prolactin have synchronous effects on stress-induced adrenal steroidogenesis, further investigation of prolactin and corticosterone may reveal a participatory role of these hormones in the pathogenesis of the genetically-programmed hypertension of SHR.