Effects of gonadectomy and sex hormone therapy on the endotoxin-stimulated hypothalamo-pituitary-adrenal axis: evidence for a neuroendocrine-immunological sexual dimorphism.
Abstract
Bacterial lipopolysaccharide (LPS) stimulates the hypothalamo-pituitary-adrenal axis by a mechanism involving the release of cytokines, which activate the CRH-ACTH system and, as a result, increase glucocorticoid secretion. In the present study we investigated the possibility that endogenous sex hormones modulate the in vivo endotoxin-stimulated adrenal and immune responses in adult BALB/c mice. In preliminary experiments we determined that the maximal glucocorticoid release in response to LPS (50 micrograms, ip) administration was reached 2 h after treatment. The endotoxin effect on the adrenal and immune responses was then tested in male, randomly cycling female, 20-day-gonadectomized and 20-day-gonadectomized mice treated with either testosterone or estradiol. In addition, in vitro experiments were performed to determine whether 1) LPS exerts any direct effect on basal and ACTH-stimulated corticosterone release, and 2) adrenal function is influenced by bilateral gonadectomy and sex steroid therapy. Our results indicate that 1) randomly cycling female mice have significantly more pronounced corticosterone secretion than males 2 h after endotoxin injection, although the tumor necrosis factor responses were similar; 2) the response of the hypothalamo-pituitary-adrenal axis to endotoxin stimulation in female mice was invariable throughout the different stages of the normal estrous cycle; 3) gonadectomy leads to enhanced (P < 0.05) adrenal and immune responses to LPS stimulation compared to the responses in shams; 4) the endotoxin-elicited adrenal and immune overresponses observed in gonadectomized mice are reversed by testosterone treatment, regardless of sex; 5) LPS does not directly modify spontaneous and ACTH-stimulated adrenal corticosterone secretion; and 6) gonadectomy alone or combined with sex steroid therapy does not increase the in vitro adrenal response to ACTH stimulation. Our findings further suggest an evident neuroendocrine-immunological sexual dimorphism during the acute phase of inflammatory processes.
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In live mice, gonadectomy and injection of bacterial endotoxin resulted in increased TNF production, which was reduced by hormone replacement.
“In live mice, gonadectomy and injection of bacterial endotoxin resulted in increased TNF production, which was reduced by hormone replacement.40”
From Testosterone replacement in hypogonadal men with angina improves ischaemic threshold and quality of life (2004) · cites this paper as [40]
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- Authors
- Spinedi, E., Suescun, M. O., Hadid, R., Daneva, T., & Gaillard, R. C.
- Affiliations
- Instituto Multidisciplinario de Biología Celular (AR)
- ORCID
- Spinedi, E
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 1992-11
- Volume
- 131
- Issue
- 5
- Pages
- 2430-2436
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W1996769397
- Cited by
- 132
- References
- 0
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 2 · 2023: 2 · 2022: 3 · 2020: 2 · 2019: 2 · 2018: 5 · 2017: 1 · 2016: 1 · 2014: 4 · 2013: 4 · 2012: 10
- FWCI
- 2.43
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- IRIS (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Keywords
- gonadectomy, sex hormone therapy, testosterone, estradiol, lipopolysaccharide, endotoxin, hypothalamic-pituitary-adrenal axis, corticosterone secretion, adrenal response, immune response, TNF-α, sex differences, estrous cycle, ACTH
- MeSH terms
- Adrenocorticotropic Hormone, Animals, Corticosterone, Endotoxins, Estradiol, Estrus, Female, Glucocorticoids, Hypothalamo-Hypophyseal System, Immune System, Lipopolysaccharides, Male, Mice, Inbred BALB C, Neurosecretory Systems, Orchiectomy, Ovariectomy, Pituitary-Adrenal System, Sex Characteristics, Testosterone, Time Factors, Tumor Necrosis Factor-alpha, Mice
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