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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Low Corticosterone Response to Stress in a Perimenopausal Rat Model Is Associated with the Hypoactivation of PaMP Region of the Paraventricular Nucleus and Can Be Corrected by Exogenous Progesterone Supplementation

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Author(s):
Rodrigues-Santos, Isabelle [1] ; Kalil-Cutti, Bruna [2] ; Anselmo-Franci, Janete Aparecida [3]
Total Authors: 3
Affiliation:
[1] Univ Sao Paulo, Dept Physiol, Sch Med Ribeirao Preto, Ribeirao Preto, SP - Brazil
[2] Univ Fed Alfenas, Inst Biomed Sci, Dept Physiol, Alfenas, SP - Brazil
[3] Univ Sao Paulo, Dept Basic & Oral Biol, Dent Sch Ribeirao Preto, Lab Neuroendocrinol, Ribeirao Preto, SP - Brazil
Total Affiliations: 3
Document type: Journal article
Source: Neuroendocrinology; JUL 2021.
Web of Science Citations: 0
Abstract

Introduction: The transition to menopause is characterized by mood, behavioral and metabolic changes. However, little is known about the changes in adrenal response to stress. Aims: The aim of the study was to evaluate, in an animal model of perimenopause induced by 4-vinylcyclohexene diepoxide (VCD), (1) the endocrine and neuronal stress system activity in response to acute restraint stress and (2) the effect of hormonal therapy in this response. Methods: Prepubertal female Wistar rats received daily injections (s.c) of oil or VCD (160 mg/kg) for 15 days. On 56th-66th days after treatment onset, the groups to be stressed received s.c implants containing placebo (PL), 17 beta-estradiol (E2), progesterone (P4), or E2P4. At 80 +/- 5 days after VCD/oil injections, stress was applied for 30 min. Blood samples were collected immediately after and 60 min after the end of stress session from the tail tip followed by transcardial perfusion with PFA 4% for the assessment of c-Fos expression in the medial and posterior parvocellular (PaMP and PaPo) subdivisions of the paraventricular nucleus (PVN) and c-Fos/tyrosine hydroxylase in the locus coeruleus (LC) using immunohistochemistry. Control groups were not stressed nor received hormone therapy. Results: While basal corticosterone levels were similar between VCD-periestropausal and control rats, the secretion in response to stress in the VCD group was lower. This effect was prevented by P4 therapy. Inversely, basal levels of P4 were lower in VCD-periestropausal rats than in the controls, and no differences were found in response to stress between the groups. As expected, 30-min restraint stress increased c-Fos immunoreactivity in all brain areas studied in both control and VCD-periestropausal rats. However, the c-Fos increase in the PaMP region was attenuated. In all areas examined, there were no significant differences in the number of c-Fos-positive neurons across hormonal therapies. Discussion/Conclusion: This is the first study to demonstrate in a perimenopausal rat model that reproductive aging is accompanied by inadequate secretion of corticosterone in response to acute stress in association with the hypoactivation of the PaMP region of the PVN, while adrenal P4 response is preserved. Moreover, P4 therapy was shown to attenuate the effects of progressive ovarian failure on adrenal functioning during stress. (AU)

FAPESP's process: 14/09772-9 - Hormonal profile, response to stress and anxiety assessment in an animal model of perimenopause.
Grantee:Janete Aparecida Anselmo Franci
Support Opportunities: Regular Research Grants