Organizational role for pubertal androgens on adult hypothalamic-pituitary-adrenal sensitivity to testosterone in the male rat

Evuarherhe, O.; Leggett, J. D.; Waite, E. J.; Kershaw, Y. M.; Atkinson, H. C.; Lightman, S. L.

doi:10.1113/jphysiol.2008.168393

Cited by 61Stress Responses and CortisolAdrenal Hormones and DisordersHypothalamic control of reproductive hormones

Organizational role for pubertal androgens on adult hypothalamic-pituitary-adrenal sensitivity to testosterone in the male rat

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Evuarherhe, O., Leggett, J. D., Waite, E. J., Kershaw, Y. M., Atkinson, H. C., Lightman, S. L.·2009·The Journal of Physiology

DOI 10.1113/jphysiol.2008.168393PMC PMC2718255

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Abstract

The inhibitory effect of androgens on the hypothalamic-pituitary-adrenal (HPA) axis in basal and stress conditions in adult male rats is well documented. Major sex-related neuroendocrine changes take place during puberty. There is a robust rise in production and secretion of gonadal steroids, which is thought to underlie numerous neural and behavioural changes brought on after puberty. The present study investigated the effect of the pubertal rise in gonadal steroid levels on the subsequent adult corticosterone profile, particularly the sensitivity of the adult HPA axis to testosterone. Animals were castrated either prepubertally (28 days) or in adulthood (11 weeks) and adult animals were subsequently treated with subcutaneous implants containing either testosterone or cholesterol. Using an automated blood sampling system, blood was collected from each freely moving, conscious rat every 10 min (i) over a 24 h period; (ii) in response to 10 min of noise stress, and (iii) following an immunological challenge with lipopolysaccharide (LPS). Analysis revealed that testosterone treatment did not significantly affect overall corticosterone release over the 24 h period in adult animals castrated before puberty in contrast to animals castrated in adulthood in which testosterone significantly suppressed corticosterone secretion. Following either a noise stress or LPS injection, testosterone treatment did not affect the hypothalamic or adrenal stress response in animals castrated prepubertally. Testosterone significantly suppressed the corticotrophin-releasing hormone and arginine vasopressin mRNA as well as the corticosterone response to LPS in castrated animals that had had their testes intact over puberty. These data provide evidence that puberty is a critical organizational period during which rising levels of gonadal steroids programme the sensitivity of the adult HPA axis to gonadal steroids in adulthood.

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The rise in testosterone during the pubertal period is key for the proper HPA axis response during adulthood.
“Subsequently, Evuarherhe et al. (2009) tested this hypothesis, and concluded that the rise in testosterone during the pubertal period is indeed key for the proper HPA axis response during adulthood.”
From Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity (2017) · cites this paper as Evuarherhe et al., 2009
The rats in our study started being treated during a critical window of pre- and peripubertal development, a period when the endocrine system is highly plastic and vulnerable to disruption.
“The rats in our study started being treated during a critical window of pre- and peripubertal development, a period when the endocrine system is highly plastic and vulnerable to disruption [56].”
From Prevention of Diet-Induced Obesity by Phytoecdysteroids 20-Hydroxyecdysone and Calonysterone—Unexpected Modulation of Androgen Balance in Normal and Obese Rats (2026) · cites this paper as [56]

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Authors: Evuarherhe, O., Leggett, J. D., Waite, E. J., Kershaw, Y. M., Atkinson, H. C., & Lightman, S. L.
Affiliations: University of Bristol (GB)
Corresponding author: Evuarherhe, O.
ORCID: Evuarherhe, O.
Kershaw, Y. M.
Atkinson, H. C.
Lightman, S. L.
Venue: The Journal of Physiology
Publisher: Wiley
Published: 2009-06-12
Volume: 587
Issue: 12
Pages: 2977-2985
ISSN: 0022-3751 (ISSN-L)
1469-7793
DOI: 10.1113/jphysiol.2008.168393
PMC: PMC2718255
OpenAlex: W1549089891
Cited by: 61
References: 33
Citations by year: 2026: 4 · 2025: 2 · 2024: 2 · 2023: 1 · 2022: 1 · 2021: 3 · 2020: 4 · 2019: 1 · 2018: 3 · 2017: 4 · 2016: 4 · 2015: 6 · 2014: 2 · 2012: 9
FWCI: 3.06
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: The Journal of Physiology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Explore Bristol Research (publishedVersion)
Bristol Research (University of Bristol) (submittedVersion)
Funders: Wellcome Trust (074112)
University of Edinburgh
Topics: Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
Keywords: puberty, androgens, testosterone, hypothalamic-pituitary-adrenal axis, corticosterone, castration, noise stress, lipopolysaccharide, corticotropin-releasing factor, vasopressin, sex steroids, male rats
MeSH terms: Androgens, Animals, Arginine Vasopressin, Body Weight, Corticosterone, Corticotropin-Releasing Hormone, Hypothalamo-Hypophyseal System, Lipopolysaccharides, Male, Orchiectomy, Pituitary-Adrenal System, Receptors, Glucocorticoid, Ribonucleotides, RNA, Messenger, Sex Differentiation, Sexual Maturation, Stress, Psychological, Testosterone, Rats, Sprague-Dawley, In Situ Hybridization, Rats

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Organizational role for pubertal androgens on adult hypothalamic-pituitary-adrenal sensitivity to testosterone in the male rat

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