Acute Stimulatory Effect of Estradiol on Striatal Dopamine Synthesis

Abstract

The acute effect of physiological doses of estradiol (E2) on the dopaminergic activity in the striatum was studied. In a first series of experiments, ovariectomized rats were injected with 17α or 17β E2 (125, 250, or 500 ng/kg of body weight, s.c.), and in situ tyrosine hydroxylase (TH) activity (determined by DOPA accumulation in the striatum after intraperitoneal administration of NSD 1015) was quantified. A dose‐dependent increase in striatal TH activity was observed within minutes after 17β (but not 17α) E2 treatment. To examine whether E2 acts directly on the striatum, in a second series of experiments, anesthetized rats were implanted in the striatum with a push‐pull cannula supplied with an artificial CSF containing [3H]tyrosine. The extracellular concentrations of total and tritiated dopamine (DA) and 3,4‐dihydroxyphenylacetic acid (DOPAC) were measured at 20‐min intervals. Addition of 10−9M 17β (but not 17α) E2 to the superfusing fluid immediately evoked an ∼50% increase in [3H]DA and [3H]DOPAC extracellular concentrations, but total DA and DOPAC concentrations remained constant. This selective increase in the newly synthesized DA and DOPAC release suggested that E2 affects DA synthesis rather than DA release. Finally, to determine whether this rapid E2‐induced stimulation of DA synthesis was a consequence of an increase in TH level of phosphorylation, the enzyme constant of inhibition by DA (Ki DA) was calculated. Incubation of striatal slices in the presence of 10−9M 17β (but not 17α) E2 indeed evoked an approximate twofold increase in the Ki DA of one form of the enzyme. It is concluded that physiological levels of E2 can act directly on striatal tissue to stimulate DA synthesis. This stimulation appears to be mediated, at least in part, by a decrease in TH susceptibility to end‐product inhibition, presumably due to phosphorylation of the enzyme. The rapid onset of this effect, and the fact that the striatum does not contain detectable nuclear E2 receptors, suggest a nongenomic action of the steroid.

Modulation of impulsivity and reward sensitivity in intertemporal choice by striatal and midbrain dopamine synthesis in healthy adults

“…Second, we did not test female participants within a fixed window of the menstrual cycle, which could impact Now bias (Smith et al 2014). However, this concern is somewhat mitigated by the fact that the FMT-PET measures used in these analyses may be downstream of the hormonal effects Kohama 1998, 1999;Pasqualini et al 1995;Shansky et al 2004;Xiao and Becker 1994) and thus predict Now/Later choice behavior independent of cycle phase. Regardless, these data add significantly to our existing model that frontal DA modulates Now bias according to a U-shaped function (Altamirano et al 2011;Kelm and Boettiger 2013;Smith and Boettiger 2012;Smith et al 2014) by identifying roles for specific extrastriatal DA terminal fields in modulating Now bias.…”

The Effects of Cocaine on Gonadal Steroid Hormones and LH in Male and Female Rhesus Monkeys

“…In vitro studies have consistently shown that physiological concentrations of estradiol stimulate dopamine synthesis/release in striatal tissue (Becker, 1990;McDermott, 1993;Pasqualini et al, 1995Pasqualini et al, , 1996. Moreover in rats, high levels of estradiol at estrus were associated with significantly higher levels of amphetaminestimulated striatal dopamine release than at diestrus (Becker and Cha, 1989).…”

Functional significance of the rapid regulation of brain estrogen action: Where do the estrogens come from?

“…There is also evidence that membrane effects of estrogens can activate intracellular signaling pathways involving cyclic AMP (cAMP; [103,170,254]), protein kinase A (PKA; [104,141,266]), the "mitogen activated protein kinases" (or MAP kinases; [39,122,153,205,260,269,276]), and the tyrosine kinases [39]. The activation of these intracellular signaling pathways results primarily in phosphorylations/dephosphorylations producing different kinds of physiological responses such as the decoupling of a receptor from its effector system [141,[171][172][173] or the modulation of the catalytic activity of an enzyme [191]. Finally, as mentioned previously, the activation of these cascades of intracellular events may result in a transcriptional activation caused, for example, by the phosphorylation of CREB (cAMP response element [CRE]-binding protein) which then acts at the level of the cAMP response element notably (CRE; [2,3,46,102,288]).…”