Inhibition of Male Sexual Behavior by Intracranial Implants of the Protein Synthesis Inhibitor Anisomycin into the Medial Preoptic Area of the Rat

McGinnis, Marilyn Y.; Kahn, David F.

doi:10.1006/hbeh.1997.1367

Cited by 39 publications

(15 citation statements)

References 44 publications

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“…Our findings are consistent with previous in vivo studies that clearly demonstrate the importance of the genotropic actions of steroids on male sexual behavior (Davidson, 1969;McGinnis and Kahn, 1997), and additionally suggest that the gene targets of E 2 action likely contain EREs. Nonetheless, E 2 also exerts rapid, non-genotropic effects on male sexual behavior.…”

Section: Estrogen Regulation Of Sexual Behavior Male Sexual Behaviorsupporting

confidence: 92%

New insights into the classical and non-classical actions of estrogen: Evidence from estrogen receptor knock-out and knock-in mice

McDevitt

Glidewell-Kenney

Jimenez

et al. 2008

Molecular and Cellular Endocrinology

123

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Estrogen receptor alpha (ERα) mediates estrogen (E 2 ) actions in the brain and is critical for normal reproductive function and behavior. In the classical pathway, ERα binds to estrogen response elements (EREs) to regulate gene transcription. ERα can also participate in several non-classical pathways, including ERE-independent gene transcription via protein-protein interactions with transcription factors and rapid, non-genotropic pathways. To distinguish between ERE-dependent and ERE-independent mechanisms of E 2 action in vivo, we have created ERα null mice that possess an ER knock-in mutation (E207A/G208A; "AA"), in which the mutant ERα cannot bind to DNA but retains activity in ERE-independent pathways (ERα −/AA mice). Understanding the molecular mechanisms of ERα action will be helpful in developing pharmacological therapies that differentiate between ERE-dependent and -independent processes. This review focuses on how the ERα −/AA model has contributed to our knowledge of ERα signaling mechanisms in estrogen regulation of the reproductive axis and sexual behavior. Keywordsestrogen receptor alpha; estrogen response element; non-classical signaling; negative feedback; sexual behaviorThe biological effects of estrogens are mediated through at least two distinct nuclear receptors, ERα and ERβ, which belong to the nuclear hormone receptor superfamily (Mangelsdorf et al., 1995). In the classical pathway of estrogen action, E 2 binds to ER, inducing conformational changes within the receptor that promote dimerization and interaction with coactivator and corepressor molecules. The ligand-receptor complex binds with high affinity to specific estrogen response elements (EREs) in the regulatory regions of target genes to either activate or repress gene expression (Glass, 1994;McKenna et al

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Section: Estrogen Regulation Of Sexual Behavior Male Sexual Behaviorsupporting

confidence: 92%

New insights into the classical and non-classical actions of estrogen: Evidence from estrogen receptor knock-out and knock-in mice

McDevitt

Glidewell-Kenney

Jimenez

et al. 2008

Molecular and Cellular Endocrinology

123

View full text Add to dashboard Cite

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“…Activation of MPO facilitates male sexual behavior in behaving animals (Malsbury, 1971;Edwards and Einhorn, 1986;Hull et al, 1997) and evokes the urogenital reflex in the anesthetized animal (Marson and McKenna, 1994). By contrast, lesions of the MPO disrupt copulation in all species examined to date (Hansen et al, 1982;Arendash and Gorski, 1983;Liu et al, 1997;McGinnis and Kahn, 1997). Because there are no direct projections from the MPO to the spinal cord motoneuronal pools that control erection and ejaculatory function, MPO initiation of male copulatory behavior must involve a relay within the neuroaxis.…”

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confidence: 85%

Distribution of gonadal steroid receptor–containing neurons in the preoptic–periaqueductal gray–brainstem pathway: A potential circuit for the initiation of male sexual behavior

Murphy

Hoffman

2001

J of Comparative Neurology

122

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The present study used anterograde and retrograde tract tracing techniques to examine the organization of the medial preoptic-periaqueductal gray-nucleus paragigantocellularis pathway in the male rat. The location of neurons containing estrogen (alpha subtype; ER alpha) and androgen receptors (AR) were also examined. We report here that injection of the anterograde tracer biotinylated dextran amine (BDA) into the medial preoptic (MPO) produced dense labeling within the periaqueductal gray (PAG); anterogradely labeled fibers terminated in close juxtaposition to neurons retrogradely labeled from the nucleus paragigantocellularis (nPGi). Dual immunostaining for Fluoro-Gold (FG) and ER alpha or FG and AR showed that over one-third of MPO efferents to the PAG contain receptors for either estrogen or androgen. In addition, approximately 50% of PAG neurons retrogradely labeled from the nPGi were immunoreactive for either ER alpha or AR. These results are the first to establish an MPO-->PAG-->nPGi circuit and further indicate that gonadal steroids can influence neuronal synaptic activity within these sites. We reported previously that nPGi reticulospinal neurons terminate preferentially within the motoneuronal pools of the lumbosacral spinal cord that innervate the pelvic viscera. Together, we propose that the MPO-->PAG-->nPGi circuit forms the final common pathway whereby MPO neural output results in the initiation and maintenance of male copulatory reflexes.

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“…Traditionally, it had been believed that E 2 facilitates mating by acting genomically after binding to its intracellular receptors, translocating to the nucleus and interacting with DNA to induce mRNA transcription and protein synthesis [23, 24, 51, 52]. Presumably, these E 2 -dependent proteins perform functions that might be conducive to the expression of certain behaviors.…”

Section: Discussionmentioning

confidence: 99%

Effects of Estrogen in the Male Rat Medial Amygdala: Infusion of an Aromatase Inhibitor Lowers Mating and Bovine Serum Albumin-Conjugated Estradiol Implants Do Not Promote Mating

Huddleston

Paisley

Clancy³

2006

Neuroendocrinology

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In male rats, copulatory behavior depends on estrogen-responsive neurons located in brain areas known to be crucial for mating. Blocking the aromatization of testosterone (T) to estradiol (E₂) either throughout the brain or within the medial preoptic area (MPO) reduces mating, whereas E₂ treatment of either the MPO or the medial amygdala (MEA) maintains sexual behavior. The effects of T aromatization in the MEA have received less attention; therefore, 2 studies were done to further elucidate the effects of E₂ in the MEA. In experiment 1, gonadally intact male rats that showed robust mating behavior were administered chronic fadrozole, a nonsteroidal aromatase inhibitor, to the MEA to stop the conversion of T to E₂ and then paired with receptive females. Infusion of fadrozole to the MEA significantly lowered mating behavior in experimental males compared to vehicle-infused control males. To further investigate the mechanism by which E₂ acts in the MEA, in experiment 2, E₂ conjugated to bovine serum albumin (BSA-E₂: a complex of E₂and a large protein that does not cross the plasma membrane, thereby restricting the action of E₂ to cell-surface signaling) was chronically administered bilaterally to the MEA of castrated, dihydrotestosterone-treated males. This treatment did not maintain mating behavior. These studies show that E₂ acts in the MEA to promote male sexual behavior and suggest an intercellular mechanism of E₂ action.

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Inhibition of Male Sexual Behavior by Intracranial Implants of the Protein Synthesis Inhibitor Anisomycin into the Medial Preoptic Area of the Rat

Cited by 39 publications

References 44 publications

New insights into the classical and non-classical actions of estrogen: Evidence from estrogen receptor knock-out and knock-in mice

New insights into the classical and non-classical actions of estrogen: Evidence from estrogen receptor knock-out and knock-in mice

Distribution of gonadal steroid receptor–containing neurons in the preoptic–periaqueductal gray–brainstem pathway: A potential circuit for the initiation of male sexual behavior

Effects of Estrogen in the Male Rat Medial Amygdala: Infusion of an Aromatase Inhibitor Lowers Mating and Bovine Serum Albumin-Conjugated Estradiol Implants Do Not Promote Mating

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