Down, But Not Out: Partial Elimination of Androgen Receptors in the Male Mouse Brain Does Not Affect Androgenic Regulation of Anxiety or HPA Activity

Chen, Chieh V.; Brummet, Jennifer L.; Jordan, Cynthia L.; Breedlove, S. Marc

doi:10.1210/en.2015-1417

Cited by 18 publications

(12 citation statements)

References 50 publications

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“…The CeL may be the activation site necessary for the beneficial effects of testosterone on extinction, as CeL neuronal activity was increased during extinction recall only in the acute experiment, which is where we observed the enhanced extinction memory. These data seem to be consistent with other findings that report that androgen receptors in the medial prefrontal cortex or hippocampus (where we also found no effects of Lupron) are not necessary for the anxiolytic effects of testosterone ((Chen et al, 2016)).…”

Section: Discussionsupporting

confidence: 93%

Acute gonadotropin-releasing hormone agonist treatment enhances extinction memory in male rats

Maeng

Taha

Cover

et al. 2017

Psychoneuroendocrinology

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Leuprolide acetate (LEU), also known as Lupron, is commonly used to treat prostate cancer in men. As a gonadotropin-releasing hormone (GnRH) receptor agonist, it initially stimulates the release of gonadal hormones, testosterone (T) and estradiol. This surge eventually suppresses these hormones, preventing the further growth and spread of cancer cells. Individuals receiving this treatment often report anxiety and cognitive changes, but LEU’s effects on the neural mechanisms that are involved in anxiety during the trajectory of treatment are not well known. In this study, we examined the acute effects of LEU on fear extinction, hypothesizing that increased T levels following a single administration of LEU will facilitate extinction recall by altering neuronal activity within the fear extinction circuitry. Two groups of naïve adult male rats underwent a 3-day fear conditioning, extinction, and recall experiment. The delayed group (n=15) received a single injection of vehicle or LEU (1.2mg/kg) 3 weeks before behavioral testing. The acute group (n=25) received an injection one day after fear conditioning, 30 minutes prior to extinction training. Following recall, the brains for all animals were collected for c-fos immunohistochemistry. Blood samples were also collected and assayed for T levels. Acute administration of LEU increased serum T levels during extinction training and enhanced extinction recall 24h later. This enhanced extinction memory was correlated with increased c-fos activity within the infralimbic cortex and amygdala, which was not observed in the delayed group. These results suggest that the elevation in T induced by acute administration of LEU can influence extinction memory consolidation, perhaps through modification of neuronal activity within the infralimbic cortex and amygdala. This may be an important consideration in clinical applications of LEU and its effects on anxiety and cognition.

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Section: Discussionsupporting

confidence: 93%

Acute gonadotropin-releasing hormone agonist treatment enhances extinction memory in male rats

Maeng

Taha

Cover

et al. 2017

Psychoneuroendocrinology

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“…An elevated anxiety-state, in particular during the light phase, was seen in the open field, novel object and elevated plus maze tests, but not in the light/dark box and corticosterone levels remained high after mild stress. In contrast, neural AR invalidation did not affect androgenic regulation of anxiety or HPA activity (Chen et al, 2016;Raskin et al, 2009;Picot et al, 2016). It has been suggested that in neural AR mutant male mice, this lack of effect may be due to residual AR expression in the amygdala and hypothalamus, but not in the hippocampus or cortex (Chen et al, 2016).…”

Section: The Hypothalamic-pituitary-adrenal (Hpa) Axis and Anxiety-rementioning

confidence: 97%

“…This conditional mutation, targeting AR in neuronal and glial precursor cells as early as embryonic day (ED) 10.5, does not interfere with the normal development of the urogenital tract. The same mouse line was generated and reported by other groups (Chen et al, 2016;Juntti et al, 2010;Karlsson et al, 2016). Deletion of the AR gene in neurons was also performed using synapsin-I-Cre transgenic mice (Yu et al, 2013).…”

Section: Genetic Modelsmentioning

confidence: 99%

Role of the androgen receptor in the central nervous system

Mhaouty-Kodja

2018

Molecular and Cellular Endocrinology

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The involvement of gonadal androgens in functions of the central nervous system was suggested for the first time about half a century ago. Since then, the number of functions attributed to androgens has steadily increased, ranging from regulation of the hypothalamic-pituitary-gonadal axis and reproductive behaviors to modulation of cognition, anxiety and other non-reproductive functions. This review focuses on the implication of the neural androgen receptor in these androgen-sensitive functions and behaviors.

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“…Residual neural AR in Nestin‐ARKO could give rise to false negative conclusions (ie, that the absence of a phenotype indicates the lack of neural androgenic mediation, when it remains possible that sufficient AR remains in neural populations). To the extent to which this has been assessed, there is indeed evidence of significant androgen sensitive neural populations in the nervous system of Nestin‐ARKO mice, including in the amygdala and hypothalamus, and more restricted interpretations of behavioural results are therefore warranted …”

Section: Neural‐specific Models Of Loss Of Functionmentioning

confidence: 99%

“…To the extent to which this has been assessed, there is indeed evidence of significant androgen sensitive neural populations in the nervous system of Nestin-ARKO mice, including in the amygdala and hypothalamus, and more restricted interpretations of behavioural results are therefore warranted. 60…”

Section: Neural-specific Models Of Loss Of Functionmentioning

confidence: 99%

Non‐neural androgen receptors affect sexual differentiation of brain and behaviour

Monks

Swift‐Gallant

2018

J Neuroendocrinology

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Although gonadal testosterone is the principal endocrine factor that promotes masculine traits in mammals, the development of a male phenotype requires local production of both androgenic and oestrogenic signals within target tissues. Much of our knowledge concerning androgenic components of testosterone signalling in sexual differentiation comes from studies of androgen receptor (Ar) loss of function mutants. Here, we review these studies of loss of Ar function and of AR overexpression either globally or selectively in the nervous system of mice. Global and neural mutations affect sociosexual behaviour and the neuroanatomy of these mice in a sexually differentiated manner. Some masculine traits are affected by both global and neural mutation, indica- is remarkable, and it is fair to say that this stems largely from the apt discussion of the findings, which captured the key questions that drive research in this field even today. One of the key conclusions of these studies was that testosterone promotes masculine behavioural traits and removes feminine behavioural traits likely by affecting the nervous system. This is the beginning of the site of action question concerning the action of testosterone in sexual differentiation of brain and behaviour. The assumption that behavioural change was the result of brain change was criticised at the time as being unwarranted because, logically, it was equally likely that sexually differentiated sexual responses could be driven, for example, by sexually differentiated genitalia. A wealth of experimental data has subsequently left no doubt that testosterone sexually differentiates the nervous system structurally, functionally and biochemically, and the field has increasingly focused on the brain as the site of testosterone action in producing masculine behavioural phenotypes. 4 Nonetheless, there is reason to

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Down, But Not Out: Partial Elimination of Androgen Receptors in the Male Mouse Brain Does Not Affect Androgenic Regulation of Anxiety or HPA Activity

Cited by 18 publications

References 50 publications

Acute gonadotropin-releasing hormone agonist treatment enhances extinction memory in male rats

Acute gonadotropin-releasing hormone agonist treatment enhances extinction memory in male rats

Role of the androgen receptor in the central nervous system

Non‐neural androgen receptors affect sexual differentiation of brain and behaviour

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