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Hormones and behavior2010; 58(5); 917-928; doi: 10.1016/j.yhbeh.2010.09.002

A component of Premarin(®) enhances multiple cognitive functions and influences nicotinic receptor expression.

Abstract: In women, ovarian hormone loss at menopause has been related to cognitive decline, and some studies suggest that estrogen-containing hormone therapy (HT) can mitigate these effects. Recently, the Women's Health Initiative study found that conjugated equine estrogens, the most commonly prescribed HT, do not benefit cognition. Isolated components of conjugated equine estrogens (tradename Premarin(®)) have been evaluated in vitro, with delta(8,9)-dehydroestrone (∆(8)E1) and equilin showing the strongest neuroprotective profiles. It has not been evaluated whether ∆(8)E1 or equilin impact cognition or the cholinergic system, which is affected by other estrogens and known to modulate cognition. Here, in middle-aged, ovariectomized rats, we evaluated the effects of ∆(8)E1 and equilin treatments on a cognitive battery and cholinergic nicotinic receptors (nAChR). Specifically, we used (125)I-labeled epibatidine binding to assay brain nicotinic receptor containing 4α and 2β subunits (α4β2-nAChR), since this nicotinic receptor subtype has been shown previously to be sensitive to other estrogens. ∆(8)E1 enhanced spatial working, recent and reference memory. ∆(8)E1 also decreased hippocampal and entorhinal cortex α4β2-nAChR expression, which was related to spatial reference memory performance. Equilin treatment did not affect spatial memory or rat α4β2-nAChR expression, and neither estrogen impacted (86)Rb(+) efflux, indicating lack of direct action on human α4β2 nAChR function. Both estrogens influenced vaginal smear profiles, uterine weights, and serum luteinizing hormone levels, analogous to classic estrogens. The findings indicate that specific isolated Premarin(®) components differ in their ability to affect cognition and nAChR expression. Taken with the works of others showing ∆(8)E1-induced benefits on several dimensions of health-related concerns associated with menopause, this body of research identifies ∆(8)E1 as a new avenue to be investigated as a potential component of HT that may benefit brain health and function during aging.
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Publication Date: 2010-09-19 PubMed ID: 20849857PubMed Central: PMC2982882DOI: 10.1016/j.yhbeh.2010.09.002Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research article investigates how isolated components of conjugated equine estrogens, specifically delta(8,9)-dehydroestrone and equilin, can impact cognitive decline related to menopause in women, by examining their effects on cognitive functions in mid-aged, ovariectomized rats. The main discovery suggests that delta(8,9)-dehydroestrone could potentially serve as a part of hormone therapy to boost brain health during aging.

Key Results of the Study

  • The research found out that delta(8,9)-dehydroestrone, a component of Premarin® (a hormone therapy medication), was able to improve spatial working, recent and reference memory in middle-aged, ovariectomized rats that served as the study subjects.
  • The same component decreased expression of cholinergic nicotinic receptors in both hippocampus and entorhinal cortex, two crucial parts of the brain involved in memory and spatial navigation, and this was related to improvements in spatial reference memory performance.
  • In contrast, equilin, a similar isolated component derived from Premarin®, showed no similar effect on spatial memory or the expression of cholinergic nicotinic receptors.
  • Interestingly, both delta(8,9)-dehydroestrone and equilin exerted influence over traditional estrogen markers such as vaginal smear profiles, uterine weights and serum luteinizing hormone levels.

Implications of the Research

  • The different impacts of delta(8,9)-dehydroestrone and equilin on cognitive function and receptor expression reveal that specific elements of Premarin® vary in their abilities to affect cognition and cholinergic nicotinic receptor expression.
  • This information could be pivotal for future investigations into hormone therapy related to women’s health, particularly in treating cognitive issues associated with menopause.
  • Delta(8,9)-dehydroestrone, in particular, presents potential as a new aspect of hormone therapy that could benefit brain health and function during aging.

Cite This Article

APA
Talboom JS, Engler-Chiurazzi EB, Whiteaker P, Simard AR, Lukas R, Acosta JI, Prokai L, Bimonte-Nelson HA. (2010). A component of Premarin(®) enhances multiple cognitive functions and influences nicotinic receptor expression. Horm Behav, 58(5), 917-928. https://doi.org/10.1016/j.yhbeh.2010.09.002

Publication

Hormones and behavior
ISSN: 1095-6867
NlmUniqueID: 0217764
Country: United States
Language: English
Volume: 58
Issue: 5
Pages: 917-928

Researcher Affiliations

Talboom, Joshua S
  • Department of Psychology, Arizona State University, Tempe, AZ 85287, USA. Joshua.Talboom@asu.edu
Engler-Chiurazzi, Elizabeth B
    Whiteaker, Paul
      Simard, Alain R
        Lukas, Ronald
          Acosta, Jazmin I
            Prokai, Laszlo
              Bimonte-Nelson, Heather A

                MeSH Terms

                • Animals
                • Behavior, Animal / drug effects
                • Behavior, Animal / physiology
                • Brain / metabolism
                • Cells, Cultured
                • Cognition / drug effects
                • Cognition / physiology
                • Drug Evaluation, Preclinical
                • Estrogens, Conjugated (USP) / chemistry
                • Estrogens, Conjugated (USP) / pharmacology
                • Female
                • Humans
                • Maze Learning / drug effects
                • Memory / drug effects
                • Memory / physiology
                • Ovariectomy
                • Rats
                • Rats, Inbred F344
                • Receptors, Nicotinic / metabolism
                • Spatial Behavior / drug effects
                • Spatial Behavior / physiology
                • Up-Regulation / drug effects

                Grant Funding

                • DA12242 / NIDA NIH HHS
                • CIHR
                • R01 AG028084 / NIA NIH HHS
                • AG028084 / NIA NIH HHS
                • R01 DA012242 / NIDA NIH HHS

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