Adrenal gland functioning in male and female offspring from dx treated mothers

Abstract

The organization and functioning of the hypothalamic-pituitary-adrenal (HPA) axis are highly conserved throughout mammalian phylogeny. There is a marked diurnal rhythm of HPA axis activity with peak levels proceeding the active part of the day in order to optimize energy mobilization and distribution. During the stress response, as the consequence of the HPA axis activation and increased adrenal glucocorticoid circulating level, energy usage is directed to promote survival. The basic functioning as well as the stress response of the HPA axis show a clear sex-specific pattern. There are significant differences in the adrenocortical glucocorticoid release, caused by diverse real or anticipated situations that disrupt homeostasis, comparing males and females. The male or female gonadal hormones influencing hypothalamic neurons, mainly CRH synthetizing neurons, pituitary hormone producing cells, primarily ACTH cells, as well as adrenocortical steroidogenic cells, determined those differences. The functioning of monoamine neurotransmitters that control HPA axis responses to acute and chronic stress in sex specific manner contributes to these differences. Prenatal life experiences also have a significant impact on postnatal HPA axis functioning determining sexually dimorphic responses. Exposures to excessive levels of maternal glucocorticoids signalize adverse environmental conditions for the developing fetus so the developmental trajectory must be adjusted to the expected postnatal surroundings. The application of synthetic glucocorticoids during gestation had similar effect on the developing fetus i.e. maturation of numerous tissues was promoted in parallel with growth retardation that occur causing permanent changes in the endocrine milieu. The aim of this study was to determine eventual sex specific dexamethasone (Dx) programming effects of rat pituitary-adrenal (PA) axis examining offspring, after fetal glucocorticoid overexposure. Thus, the activity of the PA axis was considered in adult, 90 days old male and female offspring, from control and Dx treated mothers during pregnancy. To that end, stereological parameters of the adrenal gland, as final effector of the HPA axis, as well as ACTH circulating level, aldosterone and corticosteroid output from adrenal gland, were investigated. Thus gravid females were exposed to multiple doses of synthetic glucocorticoid dexamethasone (Dx) during 16-19 days of pregnancy (3x0.5mg/kg/b.m. Dx; 16th-18th gestational day). The activity of the PA axis was considered in 90 day old male and female rat offspring from control and Ox-treated dams. The adrenal glands from both groups were subject to histological and stereological analyses. In addition, concentrations of circulating hormones as ACTH, corticosterone and aldosterone were determined with chemiluminescence method and enzyme immunoassay, respectively. The PA morphofunctional study revealed that under basal conditions, females have greater adrenal gland secretory ability due to increased adrenal weight, adrenal volume and circulating concentrations of adrenocortical hormones, corticosterone and aldosterone, in relation to males. Sex-specific programing effects after prenatal Dx exposure were pronounced in female offspring, where higher activity of the PA axis was observed after the hormonal study and adrenal gland stereological analysis; more precisely, in females, the increased ACTH forced adrenal gland synthetic activity, resulting in a corticosterone concentration as in control, reached by adrenal glands that have a reduced volume. Maternal Dx treatment did not change the hormonal output of the PA axis and adrenocortical volume in male offspring under basal conditions.