Steroid Receptor Coactivator SRC-1 Exhibits High Expression in Steroid-Sensitive Brain Areas Regulating Reproductive Behaviors in the Quail Brain

Abstract

The steroid receptor coactivator SRC-1 modulates ligand-dependent transactivation of several nuclear receptors, including the receptors for sex steroid hormones. Reducing the expression of SRC-1 by injection of specific antisense oligonucleotides markedly inhibits the effects of estrogens of the sexual differentiation of brain and behavior in rats and inhibits the activation of female sexual behavior in adult female rats. SRC-1 thus appears to be involved in both the development and activation of sexual behavior. In the Japanese quail brain, we amplified by RT-PCR a 3,411-bp fragment extending from the HLH domain to the activating domain-2 of the protein. The quail SRC-1 is closely related to the mammalian (m) SRC-1 and contains a high proportion of GC nucleotides (62.5%). Its amino acid sequence presents 70% identity with mammalian SRC-1 and contains the three conserved LXXLL boxes involved in the interaction with nuclear receptors. In both males and females, RT-PCR demonstrates a similarly high level of expression in the telencephalon, diencephalon, optic lobes, brain stem, spinal cord, pituitary, liver, kidney, adrenal gland, heart, lung, gonads and gonoducts. Males express significantly higher levels of SRC-1 in the preoptic area-hypothalamus than females. In both sexes, lower levels of expression are observed in the cerebellum and muscles. In situhybridization utilizing a mixture of four digoxigenin-labeled oligonucleotides confirms at the cellular level the widespread distribution of SRC-1 mRNA in the brain and a particularly dense expression in steroid-sensitive areas that play a key role in the control of male sexual behavior. These data confirm the presence and describe for the first time the SRC-1 distribution in the brain of an avian species. They confirm its broad, nearly ubiquitous, distribution in the entire body including the brain as could be expected for a coactivator that regulates to the action of many nuclear receptors. However this distribution is heterogeneous in the brain and sexually differentiated in at least some areas. The very dense expression of SRC-1 in limbic and mesencephalic nuclei that are associated with the control of male sexual behavior is consistent with the notion that this coactivator plays a significant role in the activation of this behavior.

Nuclear Receptor Coactivators Are Coexpressed with Steroid Receptors and Regulated by Estradiol in Mouse Brain

“…1b, f, 2b), which is consistent with other limited studies of SRC-1 mRNA in mice [59,79]. In addition, the present findings of SRC-1 expression in mouse brain are consistent with previous studies in rats [48,49,50,51,52,53,54,70,80] and birds [57,81]. SRC2-IR cells were detected throughout the mouse hippocampus, amygdala (data not shown) and hypothalamus, including the VMN, ARC and MPA (fig.…”

“…Recent work reveals that two members of this p160 family of coactivators, SRC-1 and SRC-2, are important for hormone action in brain and behavior [46,47]. SRC-1 [48,49,50,51,52,53,54,55,56,57] and SRC-2 [58,59,60] are expressed at high levels in the cortex, hypothalamus and hippocampus of rodents. Our laboratory and others have found that SRC-1 and SRC-2 are important for hormone-dependent sexual differentiation of the brain [53], gene expression in brain [54,61,62,63] and sexual behavior [54,61,62,63,64].…”

Expression of Steroid Receptor Coactivator-1 Was Regulated by Postnatal Development but Not Ovariectomy in the Hippocampus of Rats

“…In the female brain, it has been found that SRC-1 plays a role in the regulation of female sexual behavior and reproductive functions [38,39,40,41], acute stress [42] and the defeminizing actions of estradiol [20], HPA axis and thyroid function [28,43,44]. The temporal distribution pattern of hippocampal SRC-1 is highly in agreement with that of our studies of hippocampal PSD-95 [45], suggesting that it may be involved in some important functions that are based on this postsynaptic protein, because PSD-95 is important in synaptic plasticity, learning and memory [46,47].…”

Alteration in localization of steroid hormone receptors and coregulatory proteins in follicles from cows with induced ovarian follicular cysts

“…In this context, NCOAs are overexpressed in some endocrine-dependent organs and tumors and enhance cell proliferation and differentiation (Sarvilinna et al 2006, Mukherjee et al 2007, indicating an important pathophysiological role. Also, coactivator expression is known to be sexually dimorphic (Auger et al 2002, Charlier et al 2002, Duncan & Carruth 2007 and regulated by steroid hormones (Murphy & Segal 1997, Mitev et al 2003, Charlier et al 2006. However, there are limited data regarding the expression of coregulators in the bovine ovary (Hlaing et al 2001), and no studies have been performed to investigate protein localization in different ovarian compartments.…”