Cited by 108Estrogen and related hormone effectsHypothalamic control of reproductive hormonesThyroid Disorders and Treatments

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Thyroid hormone and estrogen interact to regulate behavior.

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Dellovade, T L, Zhu, Y S, Krey, L, Pfaff, D W·1996·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.93.22.12581PMC PMC38035

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Abstract

Environmental perturbations that increase plasma thyroid hormone (T3) concentrations also profoundly affect female reproductive behavior and physiology. We explored whether these effects were mediated by interactions between T3 receptor (TR) and estrogen receptor (ER). This hypothesis was of interest because the half-site of a consensus T3 response element DNA sequence is identical to an ER response element (ERE), and TRs bind to a consensus ERE. Molecular data presented in the accompanying paper [Zhu, Y.-S., Yen, P.M., Chin, W.W.& Pfaff, D.W. (1996) Proc. Natl. Acad. Sci. USA 93, 12587-12592] demonstrate that TRs and ERs are both present in rat hypothalamic nuclear extracts and that both can bind to the promoter the hypothalamic gene preproenkephalin and that interations between liganded TRs and ERs affect preproenkephalin transcription. In this paper, we show that molecular interactions between TRs and ERs are sufficient to mediate environmental effects on estrogen-controlled reproductive behavior. Ovariectomized (OVX) rats treated with high doses of T3 showed significantly lower levels of lordosis behavior in response to estradiol benzoate (EB) compared with OVX females treated with EB alone. Conversely, thyroidectomized/OVX females treated with EB showed significantly greater levels of lordosis behavior compared with OVX females treated with EB, showing the effect of endogenous T3. Thyroid hormone interference with EB-induced behavior could not be explained by a reduction in plasma E2 concentrations or by a general reduction in responsiveness of EB-sensitive tissues. Moreover, numbers of hypothalamic ER-immunoreactive cells increased dramatically following T3 treatment. These data suggest that T3 may reduce EB-dependent sexual behavior through interactions between TR and ER in the nuclei of behaviorally relevant hypothalamic neurons, envisioning for the first time a functional consequence of interactions between two nuclear hormone receptors in brain. These results also open up the possibility of molecular interactions on DNA encoding environmental signals, a new field for the study of neuronal integration.

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Self-citation

Authors: Dellovade, T. L., Zhu, Y. S., Krey, L., & Pfaff, D. W.
Affiliations: Rockefeller University (US)
New York University (US)
ORCID: Krey, L
Pfaff, D W
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 1996-10-29
Volume: 93
Issue: 22
Pages: 12581-12586
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.93.22.12581
PMC: PMC38035
OpenAlex: W2053252228
Cited by: 108
References: 30
Citations by year: 2026: 2 · 2025: 3 · 2024: 1 · 2023: 2 · 2021: 2 · 2019: 2 · 2018: 1 · 2017: 4 · 2016: 2 · 2015: 5 · 2013: 2 · 2012: 2
FWCI: 3.60
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health
Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD05751)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
Keywords: thyroid hormones, triiodothyronine, estrogen receptor, T3 receptor, receptor interaction, lordosis behavior, estradiol benzoate, female reproductive behavior, hypothalamus, preproenkephalin, thyroidectomized rats, ovariectomized rats, nuclear receptors, neural integration
MeSH terms: Animals, Estradiol, Estrogens, Female, Ovariectomy, Posture, Sexual Behavior, Animal, Thyroid Hormones, Thyroidectomy, Triiodothyronine, Rats, Sprague-Dawley, Rats

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Thyroid hormone and estrogen interact to regulate behavior.

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