The amygdala: corticotropin-releasing factor, steroids, and stress.

The possible function of corticotropin-releasing factor (CRF), adrenal steroids, and gonadal steroids in amygdala-mediated responses to anxiogenic or stressful stimuli is reviewed. The amygdala is part of an endogenous CRF circuitry within the brain that mediates neuroendocrine, autonomic, and behavioral changes in response to stress. The amygdala contains CRF-expressing neurons that communicate with widespread regions of the neural axis. High densities of CRF, CRF-binding protein, and CRF receptors are located in the amygdala. Direct injections of CRF into the amygdala produce anxiety-like behaviors. Release of endogenous CRF can be measured in the amygdala during stress. Potent anxiolytic actions are observed when CRF receptor antagonists are administered into the amygdala. CRF-containing neurons of the amygdala can be directly modulated by alterations in circulating glucocorticoids through glucocorticoid receptors, which are expressed in amygdaloid CRF-containing neurons. Gonadal steroid hormone receptors are found in the amygdala. They are not located in CRF immunoreactive neurons, but they are located adjacent to CRF-expressing neurons and in amygdaloid neurons that are likely to participate in central autonomic and neuroendocrine circuitry. Differences are noted between the steroid influences in the amygdala of male and female animals. Also, evidence is reviewed suggesting a modulatory role in the amygdala for gonadal and adrenal steroids in behavioral, autonomic, and neuroendocrine responses to anxiogenic stimuli.

Castration attenuates prolactin response but potentiates ACTH response to conditioned stress in the rat.

The purpose of this study was to examine the effect of circulating androgens on neuroendocrine, autonomic, and behavioral responses to stress. The effects of conditioned stress were studied in male Sprague-Dawley rats that were intact, gonadectomized, or gonadectomized and treated with dihydrotestosterone (DHT). Intact animals received sham surgeries. Animals were stressed 3 wk after surgery. The adrenocorticotropic hormone (ACTH) response to conditioned stress was significantly potentiated (P < 0.01) in gonadectomized males compared with sham-operated and gonadectomized DHT-treated animals. In stressed rats, plasma corticosterone levels were significantly higher (P < 0.05) in gonadectomized animals compared with DHT-treated castrates. The prolactin response to stress was decreased (P < 0.01) in gonadectomized males compared with sham-operated and gonadectomized DHT-treated rats. The stress-induced increases in plasma renin activity and concentration were not altered in gonadectomized or in gonadectomized DHT-treated animals. Nonstressed DHT-treated castrates exhibited more "fearlike" behavior compared with nonstressed sham-operated and gonadectomized animals. However, conditioned stress produced the same behavioral effects in all treatment groups. The results demonstrate that the ACTH/corticosterone, prolactin, and behavioral responses to a psychological stressor are differentially regulated by circulating androgens.

Androgen inhibits the increases in hypothalamic corticotropin-releasing hormone (CRH) and CRH-immunoreactivity following gonadectomy.

To characterize the effect of androgens on the hypothalamo-pituitary-adrenal (HPA) axis we examined the regulation of corticotropin-releasing hormone (CRH) following gonadectomy and hormone replacement. Three-month-old male Fischer 344 (F344) rats were gonadectomized (GDX) or sham GDX. Control animals remained intact. Animals were sacrificed 1, 4, 7, 10, or 21 days following surgery. GDX rats had significantly elevated (p < 0.05) levels of hypothalamic CRH 21 days after surgery compared to intact and sham-operated rats. In a second study, 3-month-old male F344 rats were GDX and treated with the non-aromatizable androgen, dihydrotestosterone (DHT), using a Silastic capsule containing crystalline DHT propionate subcutaneously implanted in each animal's back. Control animals were GDX and sham-treated or left intact (INT). Three weeks following gonadectomy, CRH levels in the hypothalamus of GDX rats showed a significant increase (p < 0.05) compared to intact animals. DHT treatment, beginning at the time of gonadectomy prevented this increase. CRH or arginine vasopressin (AVP) immunoreactivity was examined using immunocytochemistry. The number of CRH-immunoreactive (IR) cells in the paraventricular nucleus (PVN) of GDX, DHT-treated animals was significantly decreased (p < 0.05) compared to GDX rats. No differences were seen between treatment groups in CRH-IR cell numbers in the bed nucleus of the stria terminalis or the central amygdaloid nucleus or in AVP-IR cell numbers in the PVN. These data demonstrate that long-term castration increases hypothalamic CRH content and CRH-IR cell numbers in the PVN by removal of an androgen-dependent repression.

Localization of androgen receptor within peptidergic neurons of the rat forebrain.

This study tested for the presence of androgen receptor-immunoreactivity in somatostatin, galanin, vasopressin, corticotropin-releasing hormone, and oxytocin neurons in the rat forebrain. The brains of adult male Sprague-Dawley rats were fixed with 4% paraformaldehyde. Androgen receptor was visualized in coronal sections using nickel intensification of diaminobenzidine, and the neuropeptides were identified using a brown diaminobenzidine reaction product. Androgen receptor was localized to the nuclei of neurons in the septum, amygdala, cortex, hippocampus, and hypothalamus. The majority of somatostatin-containing neurons in the periventricular hypothalamic nucleus also contained androgen receptor. Androgen receptor was also found within galanin-expressing cells in the bed nucleus of the stria terminalis and in the amygdala. Androgen receptor was not observed in corticotropin-releasing hormone, vasopressin, or oxytocin neurons in all areas examined. The data suggest that androgens may be capable of directly regulating somatostatin-expressing neurons of the periventricular nucleus of the hypothalamus and galanin-containing neurons of the bed nucleus of the stria terminalis and amygdala.