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Primary Culture of Rat Adrenocortical Cells and Assays of Steroidogenic Functions
Published on: March 12, 2019
Corticosterone secretion induced by chronic isolation in neonatal rats is sexually dimorphic and accompanied by
1Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Insights
Repeated isolation during rat pups' stress hyporesponsive period sensitizes the hypothalamic-pituitary-adrenal (HPA) axis, leading to increased corticosterone, particularly in females. This response is centrally mediated by ACTH.
Area of Science:
- Neuroscience
- Endocrinology
- Developmental Biology
Background:
- Neonatal stress exposure can lead to long-term neuroendocrine and behavioral changes.
- The stress hyporesponsive period (SHRP) in rats is a critical window for stressor effects.
- Previous research indicated sensitization of corticosterone release following repeated neonatal isolation.
Purpose of the Study:
- To investigate the hypothalamic-pituitary-adrenal (HPA) axis responsivity during the SHRP after repeated isolation.
- To determine if increased adrenocortical response is mediated by pituitary ACTH secretion.
- To examine the central mechanisms and sexual dimorphism of stress responses in neonatal rats.
Main Methods:
- Rat pups were subjected to daily 1-hour isolation from postnatal days 4-8.
- Hormonal levels (corticosterone, ACTH) and Fos immunoreactivity were measured after isolation or pharmacological challenges on postnatal day 9.
- Controls included unhandled and handled pups.
Main Results:
- Repeated isolation significantly increased corticosterone levels on postnatal day 9, a response observed only in females (sexual dimorphism).
- Chronically isolated pups of both sexes showed increased plasma ACTH following isolation, suggesting central mediation.
- Pharmacological activation of serotonin receptors robustly stimulated ACTH and corticosterone secretion and induced Fos expression in the paraventricular nucleus (PVN).
Conclusions:
- Chronic isolation stress during the SHRP stimulates the neonatal HPA axis, with a sexually dimorphic adrenal response.
- The hormonal response to isolation is centrally mediated, involving ACTH.
- PVN neurons are capable of expressing Fos immunoreactivity on postnatal day 9 following potent HPA axis activation.
Abstract:
Rat pups repeatedly subjected to brief periods of isolation during the stress hyporesponsive period (SHRP) exhibit varied neuroendocrine and behavioral changes as neonates and as adults. For example, neonatal rats exhibit increased circulating corticosterone after 1-h isolation on postnatal day 9 (P9) only if they were isolated daily from P2 to P8 [McCormick, C.M., Kehoe, P., Kovacs, S., 1998. Corticosterone release in response to repeated, short episodes of neonatal isolation: evidence of sensitization. Int. J. Dev. Neurosci. 16, 175-185]. It is not known if the increase in adrenocortical response on P9 following repeated isolation is mediated by increased pituitary ACTH secretion. The present study examined the responsivity of the hypothalamic-pituitary-adrenal (HPA) axis during the SHRP following brief, repeated isolation or acute pharmacological manipulation. Removal from the nest for 1 h daily on P4-8 increased circulating corticosterone after 1-h isolation on P9 by approximately twofold. Neither unhandled nor handled controls showed a corticosterone response to 1-h isolation on P9. The increased corticosterone was sexually dimorphic, with only females showing the sensitization response. Other findings suggest that the hormonal response is centrally mediated; chronically isolated pups of both sexes exhibit increased plasma ACTH following 1-h isolation on P9. While we could not detect an increase in Fos immunoreactivity (IR) on P9 in the hypothalamic paraventricular nucleus (PVN) of chronically isolated pups, acute pharmacological activation of serotonin 2A/2C receptors produced robust activation of ACTH and corticosterone secretion as well as expression of Fos in the PVN on P9. We conclude that chronic isolation stress limited to the SHRP stimulates the neonatal HPA axis, and that the adrenal response is sexually dimorphic. In addition, PVN neurons can express Fos IR on P9 in response to a very potent activation of the HPA axis.
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