Circulating estrogens in a male songbird originate in the brain.

Abstract

Gonadal steroids act on brain to regulate the development and expression of vertebrate reproductive behavior. In addition, steroid targets in brain are an integral part of the feedback regulation of gonadal steroidogenesis. The actions of androgens in brain are often mediated by enzymatic activation or inactivation of circulating hormone, including local conversion of androgen to estrogen. We now report that in zebra finches, the brain synthesizes large quantities of estrogen from androgen and releases this estrogen into blood. Since there appears to be no other significant source of estrogen synthesis in adult male zebra finches, it is likely that the brain directly controls plasma levels of this steroid by contributing most or all ofthe high levels ofestrogen found in the circulation. and see also refs. 27 and 28). Because aromatase activity in male TEL was high, similar to ovary, and absent elsewhere, we have postulated that the brain is the origin of E seen in the circulation of male songbirds (25).To test this hypothesis, we developed methods to measure aromatase activity in zebra finches in vivo and have used these experimental approaches to determine (i) whether E made from androgen in brain can be found in the circulation; (ii) whether physiological blood levels of aromatizable androgen (AA) can be converted by brain to E and released into the circulation; and (iii) whether in vivo measures of E synthesis could reveal sites of aromatase activity undetected by in vitro assays, especially in tissues outside of brain.The actions of estrogens (Es) on brain are essential for the development and expression of song in male passerine (oscine) birds. In the zebra finch (Poephila guttata), males sing a courtship song that females lack. Correspondingly, the telencephalic neural system controlling song is much larger in males than females (1). However, ifyoung females are treated with E, they develop a masculinized neural song system and the capacity to sing as adults (2-6). These E effects on the song system are extensive; they influence neuron survival, size, dendritic arbor, or hormone sensitivity within several brain structures (7-11). Thus, Es are thought to be the normal masculinizing hormone in developing males. Such E effects on the male brain are not unusual, but in the vast majority of vertebrates, Es in males circulate at low or undetectable levels. However, the enzyme that catalyzes the conversion of androgen to E, aromatase cytochrome P450, can be present near E targets in the brain. By controlling local concentrations of E, aromatization controls occupancy of nearby E receptors and, hence, regulates those actions of testicular androgens that are mediated by E receptors (12-16).By contrast, in both developing and adult songbirds, males have high estradiol (E2) levels in blood, often equal to or greater than those seen in adult breeding females (17-19). Because high E levels in blood may be involved with brain sexual differentiation (20) and with the capacity of birds to learn song (21), there ha...

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“…In fact, E2 concentrations obtained from dialysis measurements depend on the dynamics of the exchange between interstitial fluid and the dialysis fluid and, therefore, may not directly represent the actual hormone concentrations in the brain. This interpretation is consistent with previous findings indicating that E2 levels are significantly higher in the jugular than in the carotid of zebra finches, suggesting that estrogens produced in the brain are indeed released in the entire body (Schlinger and Arnold, 1992). Importantly, it is also possible that the effective concentration of estrogens at the synaptic level (aromatase-positive synapses) may be markedly higher than those levels measured in the plasma or even in the brain of zebra finches (Cornil et al, 2006).…”

A genetically female brain is required for a regular reproductive cycle in chicken brain chimeras

“…Pioneering work has shown the synthesis of E2 from T in the songbird brain 44 . Subsequently, several neurosteroids as well as the enzymes necessary for their production from cholesterol have been found in quail brain 29,45 , and there is evidence for de novo synthesis of E2 from cholesterol in songbird brain 28,46 .…”

Activities of 3β-HSD and aromatase in slices of developing and adult zebra finch brain

“…There is considerable evidence suggesting that these estrogens are formed in the brain (Holloway and Clayton, 2001;Schlinger and Arnold, 1991;1992a). Aromatase catalyzes the conversion of androgens into estrogens.…”

“…Aromatase catalyzes the conversion of androgens into estrogens. This enzyme is expressed in large amounts in the zebra finch telencephalon according to activity studies of brain Correspondence: Barney A. Schlinger, Department of Physiological Science, UCLA, Los Angeles, CA 90095-1606, 310-825-5716 (phone), 310-206-9184 (FAX), schlinge@physci.ucla.edu.homogenates (Schlinger and Arnold, 1991;1992a;Vockel et al, 1990), cellular subfractions (Schlinger and Arnold, 1992b), and dissociated primary cell cultures (Schlinger et al, 1994).…”