Modulation of steroid action in the central and peripheral nervous systems by nuclear receptor coactivators

Tetel, Marc J.

doi:10.1016/j.psyneuen.2009.05.022

Cited by 21 publications

(8 citation statements)

References 131 publications

(199 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This specificity may depend on the steroidogenic enzymes and/or androgen receptor co-factors that are expressed (Tremblay et al, 1977; Martini et al, 1993; Pozzi et al, 2003; O’Bryant and Jordan, 2005; Tetel, 2009). Furthermore, as discussed above, the various elements of the SNB neuromuscular system are likely regulated by androgenic action at different loci.…”

Section: Discussionmentioning

confidence: 99%

Testosterone metabolites differentially maintain adult morphology in a sexually dimorphic neuromuscular system

Verhovshek

Buckley

Sergent

et al. 2010

Developmental Neurobiology

View full text Add to dashboard Cite

The lumbar spinal cord of rats contains the sexually dimorphic, steroid-sensitive spinal nucleus of the bulbocavernosus (SNB). Androgens are necessary for the development of the SNB neuromuscular system, and in adulthood, continue to influence the morphology and function of the motoneurons and their target musculature. However, estrogens are also involved in the development of the SNB system, and are capable of maintaining function in adulthood. In this experiment we assessed the ability of testosterone metabolites, estrogens and non-aromatizable androgens, to maintain neuromuscular morphology in adulthood. Motoneuron and muscle morphology was assessed in adult normal males, sham-castrated males, castrated males treated with testosterone, dihydrotestosterone, estradiol, or left untreated, and gonadally intact males treated with the 5α-reductase inhibitor finasteride or the aromatase inhibitor fadrozole. After 6 weeks of treatment, SNB motoneurons were retrogradely labeled with cholera toxin-HRP and reconstructed in three dimensions. Castration resulted in reductions in SNB target muscle size, soma size, and dendritic morphology. Testosterone treatment after castration maintained SNB soma size, dendritic morphology, and elevated target muscle size; dihydrotestosterone treatment also maintained SNB dendritic length, but was less effective than testosterone in maintaining both SNB soma size and target muscle weight. Treatment of intact males with finasteride or fadrozole did not alter the morphology of SNB motoneurons or their target muscles. In contrast, estradiol treatment was completely ineffective in preventing castration-induced atrophy of the SNB neuromuscular system. Together, these results suggest that the maintenance of adult motoneuron or muscle morphology is strictly mediated by androgens.

show abstract

Section: Discussionmentioning

confidence: 99%

Testosterone metabolites differentially maintain adult morphology in a sexually dimorphic neuromuscular system

Verhovshek

Buckley

Sergent

et al. 2010

Developmental Neurobiology

View full text Add to dashboard Cite

show abstract

“…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.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2011

Self Cite

View full text Add to dashboard Cite

Background/Aims: The steroid hormones, including estradiol (E) and progesterone, act in the brain to regulate female reproductive behavior and physiology. These hormones mediate many of their biological effects by binding to their respective intracellular receptors. The receptors for estrogens (ER) and progestins (PR) interact with nuclear receptor coactivators to initiate transcription of steroid-responsive genes. Work from our laboratory and others reveals that nuclear receptor coactivators, including steroid receptor coactivator-1 (SRC-1) and SRC-2, function in brain to modulate ER-mediated induction of the PR gene and hormone-dependent behaviors. In order for steroid receptors and coactivators to function together, both must be expressed in the same cells. Methods: Triple-label immunofluorescence was used to determine if E-induced PR cells also express SRC-1 or SRC-2 in reproductively relevant brain regions of the female mouse. Results: The majority of E-induced PR cells in the medial preoptic area (61%), ventromedial nucleus of the hypothalamus (63%) and arcuate nucleus (76%) coexpressed both SRC-1 and SRC-2. A smaller proportion of PR cells expressed either SRC-1 or SRC-2, while a few PR cells expressed neither coactivator. In addition, compared to control animals, 17β-estradiol benzoate (EB) treatment increased SRC-1 levels in the arcuate nucleus, but not the medial preoptic area or the ventromedial nucleus of the hypothalamus. EB did not alter SRC-2 expression in any of the three brain regions analyzed. Conclusions: Taken together, the present findings identify a population of cells in which steroid receptors and nuclear receptor coactivators may interact to modulate steroid sensitivity in brain and regulate hormone-dependent behaviors in female mice. Given that cell culture studies reveal that SRC-1 and SRC-2 can mediate distinct steroid-signaling pathways, the present findings suggest that steroids can produce a variety of complex responses in these specialized brain cells.

show abstract

“…During the fifth meeting, endocrine disruptors were considered among the wide family of steroid receptors coactivators (67), in particular those modulating the expression of sexually dimorphic social and emotional behaviours (68). Finally, during the last meeting, whose proceedings are collected in this special issue of the Journal of Neuroendocrinology , a round table on endocrine disrupter action on behaviour and neuroendocrine system was organised (69).…”

Section: Brain and Behaviour Targets For The Endocrine Disruptersmentioning

confidence: 99%

“…The importance of co‐regulatory factors to influence nSRs action has been discussed (159). How the actions of steroids in the brain via sNRs can also involve coactivators, which modulate hormone‐dependent gene expression in the brain and reproductive behaviour in rodents (67) and galliforms (159), and co‐repressors, such as chromatin‐binding factor mediation of the epigenetic organisation of sex differences in the brain (160), has been the topic of recent symposia. Thus, as evidence has emerged regarding the actions of steroids via nSRs, these topics have been of ongoing interest and discussion.…”

Section: Interactions With Classical and Nonclassical Steroid Receptorsmentioning

confidence: 99%

Milestones on Steroids and the Nervous System: 10 Years of Basic and Translational Research

Panzica

Balthazart

Frye

et al. 2011

J Neuroendocrinology

View full text Add to dashboard Cite

During the last 10 years, the conference on ‘Steroids and Nervous System’ held in Torino (Italy) has been an important international point of discussion for scientists involved in this exciting and expanding research field. The present review aims to recapitulate the main topics that have been presented through the various meetings. Two broad areas have been explored: the impact of gonadal hormones on brain circuits and behaviour, as well as the mechanism of action of neuroactive steroids. Relationships among steroids, brain and behaviour, the sexual differentiation of the brain and the impact of gonadal hormones, the interactions of exogenous steroidal molecules (endocrine disrupters) with neural circuits and behaviour, and how gonadal steroids modulate the behaviour of gonadotrophin‐releasing hormone neurones, have been the topics of several lectures and symposia during this series of meetings. At the same time, many contributions have been dedicated to the biosynthetic pathways, the physiopathological relevance of neurosteroids, the demonstration of the cellular localisation of different enzymes involved in neurosteroidogenesis, the mechanisms by which steroids may exert some of their effects, both the classical and nonclassical actions of different steroids, the role of neuroactive steroids on neurodegeneration, neuroprotection, and the response of the neural tissue to injury. In these 10 years, this field has significantly advanced and neuroactive steroids have emerged as new potential therapeutic tools to counteract neurodegenerative events.

show abstract

Modulation of steroid action in the central and peripheral nervous systems by nuclear receptor coactivators

Cited by 21 publications

References 131 publications

Testosterone metabolites differentially maintain adult morphology in a sexually dimorphic neuromuscular system

Testosterone metabolites differentially maintain adult morphology in a sexually dimorphic neuromuscular system

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

Milestones on Steroids and the Nervous System: 10 Years of Basic and Translational Research

Contact Info

Product

Resources

About