A combination of laboratory and field investigations of birds has shown that expression of behavior such as territorial aggression can occur throughout the year in many species and in different life history stages. Although it is well known that testosterone regulates territorial aggression in males during the breeding season, the correlation of plasma testosterone and aggression appears to be limited to periods of social instability when a male is challenged for his territory by another male, or when mate-guarding a sexually receptive female. How essentially identical aggression is modulated in non-breeding life history stages is not fully resolved, but despite low circulating levels of testosterone outside the breeding season, expression of territorial aggression does appear to be dependent upon aromatization of testosterone and an estrogen receptor-mediated mechanism. There is accumulating evidence that prolonged high levels of circulating testosterone may incur costs that may potentially reduce lifetime fitness. These include interference with paternal care, exposure to predators, increased risk of injury, loss of fat stores and possibly impaired immune system function and oncogenic effects. We propose six hypotheses to explain how these costs of high testosterone levels in blood may be avoided. These hypotheses are testable and may reveal many mechanisms resulting from selection to avoid the costs of testosterone. It should also be noted that the hypotheses are applicable to vertebrates in general, and may also be relevant for other hormones that have a highly specialized suite of actions in one life history stage (such as breeding), but also have a limited action in other life history stages when the full spectrum of effects would be inappropriate.

Taves MD, Gomez-Sanchez CE, Soma KK. Extra-adrenal glucocorticoids and mineralocorticoids: evidence for local synthesis, regulation, and function. Am J Physiol Endocrinol Metab 301: E11-E24, 2011. First published May 3, 2011; doi:10.1152/ajpendo.00100.2011.-Glucocorticoids and mineralocorticoids are steroid hormones classically thought to be secreted exclusively by the adrenal glands. However, recent evidence has shown that corticosteroids can also be locally synthesized in various other tissues, including primary lymphoid organs, intestine, skin, brain, and possibly heart. Evidence for local synthesis includes detection of steroidogenic enzymes and high local corticosteroid levels, even after adrenalectomy. Local synthesis creates high corticosteroid concentrations in extra-adrenal organs, sometimes much higher than circulating concentrations. Interestingly, local corticosteroid synthesis can be regulated via locally expressed mediators of the hypothalamic-pituitary-adrenal (HPA) axis or renin-angiotensin system (RAS). In some tissues (e.g., skin), these local control pathways might form miniature analogs of the pathways that regulate adrenal corticosteroid production. Locally synthesized glucocorticoids regulate activation of immune cells, while locally synthesized mineralocorticoids regulate blood volume and pressure. The physiological importance of extra-adrenal glucocorticoids and mineralocorticoids has been shown, because inhibition of local synthesis has major effects even in adrenal-intact subjects. In sum, while adrenal secretion of glucocorticoids and mineralocorticoids into the blood coordinates multiple organ systems, local synthesis of corticosteroids results in high spatial specificity of steroid action. Taken together, studies of these five major organ systems challenge the conventional understanding of corticosteroid biosynthesis and function.aldosterone; brain; bursa of Fabricius; corticosterone; cortisol; heart; immunosteroids; intestine; neurosteroids; skin; stress; thymus CORTICOSTEROIDS ARE STEROID HORMONES produced in the adrenal cortex and are of two types, glucocorticoids and mineralocorticoids. Glucocorticoids, such as corticosterone and cortisol, have numerous effects and can act on nearly all cells in the body. For example, glucocorticoids regulate metabolic activity, immune function, and behavior (84). Circulating glucocorticoid levels increase in response to a variety of stressors under control of the hypothalamic-pituitary-adrenal (HPA) axis. Hypothalamic release of corticotropin-releasing hormone (CRH) triggers pituitary release of adrenocorticotropic hormone (ACTH), which stimulates glucocorticoid production by the zona fasciculata of the adrenals. The adrenals can secrete cortisol, corticosterone, or both, depending on the species.Mineralocorticoids, such as aldosterone, promote sodium reabsorption in transporting epithelia of the kidneys, salivary glands, and large intestine. Sodium reabsorption is followed by passive reabsorption of water. Circulating aldosterone concentrations...

Reproduction in vertebrates is regulated by the hypothaamcpitultaryonadal axis via neural and hormonal feedback. This axis is also subject to exogenous Influences, particularly social signas. In the African cichlid fish Haplochronus burtoni, gonadal development in males is socafly regulated. A small fraction of the males, which are brightiy colored, maintain territories and aggrssively dominate inconspicuoudy colored nonterritorial males. Here we show through manipulation of the social and endocrine environment that changes in social status and gonadal state are accompanied by soma size changes in a population of gonadotropin-releasing hormone-containing neurons in the ventral forebrain. In territorial males, these cells are slnflcantly larger than in nonterritorial males. When an animal switches from being territorial to nonterritorlal through a change in social situation, these cells shrink; in animals that change from nonterritorial to territorial status, the cells enlarge. These gonadotropin-releasing hormone-containing cells project to the pituitr and are ulimat responsible for regulating gonadal growth. This mechanism of socially induced cell size change provides the potential for relatively quick adaptive changes in the neuroendocrine system without nerve cell addition or death. Since the structure of this regulatory axis is conserved among all vertebrates, other species with socially modulated reproductive physiology may exhibit a simiar form of physoogical regulation.

Dehydroepiandrosterone (DHEA) is a precursor to sex steroids such as androstenedione (AE), testosterone (T), and estrogens. DHEA has potent effects on brain and behavior, although the mechanisms remain unclear. One possible mechanism of action is that DHEA is converted within the brain to sex steroids. 3beta-Hydroxysteroid dehydrogenase/Delta5-Delta4 isomerase (3beta-HSD) catalyzes the conversion of DHEA to AE. AE can then be converted to T and estrogen within the brain. We test the hypothesis that 3beta-HSD is expressed in the adult brain in a region- and sex-specific manner using the zebra finch (Taeniopygia guttata), a songbird with robust sex differences in song behavior and telencephalic song nuclei. In zebra finch brain, DHEA is converted by 3beta-HSD to AE and subsequently to estrogens and 5alpha- and 5beta-reduced androgens. 3beta-HSD activity is highest in the diencephalon and telencephalon. In animals killed within 2-3 min of disturbance, baseline 3beta-HSD activity in portions of the telencephalon is higher in females than males. Acute restraint stress (10 min) decreases 3beta-HSD activity in females but not in males, and in stressed animals, telencephalic 3beta-HSD activity is greater in males than in females. Thus, the baseline sex difference is rapidly reversed by stress. To our knowledge, this is the first demonstration of 1) brain region differences in DHEA metabolism by 3beta-HSD, 2) rapid modulation of 3beta-HSD activity, and 3) sex differences in brain 3beta-HSD and regulation by stress. Songbirds are good animal models for studying the regulation and functions of DHEA and neurosteroids in the nervous system.