Sex differences in the pituitary-adrenal response following acute antidepressant treatment in sheep

Broadbear, Jillian Helen; Hutton, Lisa Cathleen; Clarke, I. J.; Canny, Benedict J.

doi:10.1007/s00213-003-1613-9

Cited by 13 publications

(18 citation statements)

References 49 publications

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“…Significantly different responses between the various treatments were seen in the absence, but not presence of T (*vehicle versus sertraline, # 5 versus 10 mg/kg sertraline:P<0.05) cortisol to a lower sertraline dose (5 mg/kg) than did the rams. These results are consistent with an earlier study in which we reported that sertraline (2 and 5 mg/kg) stimulated ACTH and cortisol secretion in OVX ewes, but was ineffective in castrated rams (Broadbear et al 2004). In the present study, a stimulatory effect of sertraline on ACTH and cortisol secretion was detected in males, but only when the dose of sertraline from our earlier study was doubled.…”

Section: Discussionsupporting

confidence: 95%

“…Despite this difference in HPA axis activation between male and female sheep, acute treatment with sertraline resulted in a similar increase in prolactin secretion in all sheep (Broadbear et al 2004). The prolactin results imply that there was no sex difference in the effects of sertraline on 5-HT availability per se, but that the sex difference measured in the HPA axis response to sertraline probably occurred at the pituitary or hypothalamic level.…”

Section: Discussionmentioning

confidence: 86%

“…In our earlier study, in which the effects of lower doses of sertraline and imipramine on ACTH, cortisol and prolactin were measured, treatment with imipramine did not change any of the neuroendocrine markers (Broadbear et al 2004). Imipramine does not always stimulate the HPA axis when it is administered via non-intravenous routes (Dredge et al 1999), and our conclusion was that the dose used in this earlier study was inadequate.…”

Section: Discussionmentioning

confidence: 96%

“…Blood samples from all time points were assayed to determine plasma cortisol concentrations in animals from all treatment conditions. The assay procedure that was used to measure plasma cortisol levels has been published previously (Broadbear et al 2004). The sensitivity of the assay was 0.2 ng/ml.…”

Section: Radioimmunoassaysmentioning

confidence: 99%

“…In addition, there remains a paucity of data regarding sex differences in the effects of antidepressants on other endpoints, such as the HPA axis. In a recent study, it was found that acute administration of sertraline to gonadectomised ewes (without sex hormone replacement) increased plasma cortisol and ACTH concentrations in a dose-dependent manner (Broadbear et al 2004). This effect was not seen in castrated rams.…”

Section: Introductionmentioning

confidence: 97%

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Antidepressants, sex steroids and pituitary?adrenal response in sheep

et al. 2004

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The importance of sex differences in major affective diseases such as depression is providing a new focus for investigating the interactions between sex, sex steroids and antidepressants. In this study, we examined the acute effects of sertraline, a selective serotonin reuptake inhibitor (SSRI) and imipramine, a tricyclic antidepressant (TCA) on the endocrine endpoints, adrenocorticotropin (ACTH) and cortisol secretion in gonadectomised male and female sheep. Each sheep was treated with an acute subcutaneous (s.c.) injection containing vehicle, sertraline (5 and 10 mg/kg), or imipramine (10 mg/kg) in the presence and absence of sex steroid replacement. In males, SSRI treatment consisted of testosterone (2 x 200 mg s.c. pellets), and in females, estradiol (1 cm s.c. implant) plus an intravaginal controlled internal drug release device containing 0.3 g progesterone. ACTH and cortisol were measured in jugular blood. Female sheep responded to sertraline treatment with dose-dependent ACTH and cortisol increases that were unchanged by sex steroid replacement. In castrated males, however, only the highest dose of sertraline increased ACTH and cortisol, and this increase was abolished in the presence of testosterone replacement. Imipramine affected neither ACTH nor cortisol secretion in either the sex or sex steroid condition. We conclude that the sex and sex steroid-related differences in the male and female responses to sertraline treatment may reflect sex and sex steroid dependent differences in serotonergic activation of the HPA axis. This highlights the potential significance of sex and circulating sex steroids in modulating neuroendocrine responses to antidepressants, and may have an impact on our understanding of the actions of these drugs in men and women.

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Section: Discussionsupporting

confidence: 95%

Section: Discussionmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 96%

Section: Radioimmunoassaysmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

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Antidepressants, sex steroids and pituitary?adrenal response in sheep

et al. 2004

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A placebo-controlled study of sertraline’s effect on cortisol response to the dexamethasone/corticotropin-releasing hormone test in healthy adults

et al. 2011

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Rationale The dexamethasone/corticotropin-releasing hormone (Dex/CRH) test is a neuroendocrine probe involving serial blood sampling of cortisol during a standardized pharmacological challenge without inducing psychological distress in humans. Some past studies in depressed patients have shown a “normalization” or decrease in cortisol response to the Dex/CRH test following successful treatment with an antidepressant. Studies in nondepressed healthy adult samples have also shown aberrant cortisol reactivity to be associated with depression risk factors. These findings prompted research into the use of the Dex/CRH test as a tool for developing antidepressant drugs. Objectives In this study, the Dex/CRH test was evaluated with regard to its potential utility for drug development in nonclinical samples. Methods The Dex/CRH test was administered before and after 6 weeks of blinded treatment with either sertraline 100 mg/day or matching placebo in 22 healthy adults (13 women, nine men). Results Cortisol response to the Dex/CRH test increased following treatment with standard doses of sertraline, compared to placebo, after controlling for age and sex. Conclusions The observed pattern of change contrasts with results from published studies in depressed patients and with our initial hypothesis.

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Sertraline alleviated osmophobia caused by partial hypopituitarism with isolated ACTH deficiency

Kuo

Chang

Chen

et al. 2013

General Hospital Psychiatry

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Sex differences in the pituitary-adrenal response following acute antidepressant treatment in sheep

Abstract: These data suggest that the HPA axes of females are more sensitive to the stimulatory effects of serotonin following acute treatment with the SSRI, sertraline.

Cited by 13 publications

References 49 publications

Antidepressants, sex steroids and pituitary?adrenal response in sheep

Antidepressants, sex steroids and pituitary?adrenal response in sheep

A placebo-controlled study of sertraline’s effect on cortisol response to the dexamethasone/corticotropin-releasing hormone test in healthy adults

Sertraline alleviated osmophobia caused by partial hypopituitarism with isolated ACTH deficiency

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