Postmenopausal hypertrophy of neurons expressing the estrogen receptor gene in the human hypothalamus

RANCE, NAOMI E.; McMULLEN, NATHANIEL T.; SMIALEK, JOHN E.; PRICE, DONALD L.; YOUNG, W. SCOTT

doi:10.1210/jcem-71-1-79

Cited by 148Hypothalamic control of reproductive hormonesEstrogen and related hormone effectsMenopause: Health Impacts and Treatments

Postmenopausal hypertrophy of neurons expressing the estrogen receptor gene in the human hypothalamus

RANCE, NAOMI E., McMULLEN, NATHANIEL T., SMIALEK, JOHN E., PRICE, DONALD L., YOUNG, W. SCOTT·1990·The Journal of Clinical Endocrinology & Metabolism

DOI 10.1210/jcem-71-1-79

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Abstract

Computer microscopy and in situ hybridization were used to investigate neuronal hypertrophy in the infundibular nucleus of postmenopausal women. In the first experiment, hypothalami from premenopausal (n = 3) and postmenopausal (n = 3) women were formalin fixed, paraffin embedded, serially sectioned, and stained with cresyl violet. Soma areas of more than 3500 neurons were digitized using an image-combining computer microscope. The mean cross-sectional area of infundibular neurons in the postmenopausal women was 30% greater than that in premenopausal women, with no change in cell density. The mean cross-sectional area of mammillary neurons was unchanged, indicating that the infundibular neuronal hypertrophy was not an artifact of tissue processing. In the second experiment, hypothalami from premenopausal (n = 3) and postmenopausal (n = 2) women were frozen, serially sectioned, and incubated with a 48-base synthetic cDNA probe complementary to estrogen receptor (ER) mRNA. Adjacent sections were incubated with a cDNA probe complementary to GnRH mRNA. Morphometric analysis revealed that the mean cross-sectional area of infundibular neurons expressing the ER gene in the postmenopausal women was twice as large as the mean area in premenopausal hypothalami. The hypertrophied neurons did not contain GnRH mRNA. Finally, analysis of the infundibular nucleus from an oophorectomized 38-yr-old woman also revealed hypertrophied neurons containing ER mRNA. These data support the hypothesis that hypertrophy of infundibular neurons in postmenopausal women is secondary to loss of the inhibitory feedback of ovarian steroids.

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Morphologic studies show hypertrophy of a subpopulation of neurons in the infundibular (arcuate) nucleus of postmenopausal women.
“Morphologic studies of postmortem hypothalamic tissues from premenopausal and postmenopausal women have shown hypertrophy of a subpopulation of neurons in the infundibular (arcuate) nucleus of the postmenopausal group (Rance et al., 1990; Sheehan and Kovács, 1966).”
From Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes (2013) · cites this paper as Rance et al., 1990
The hypertrophied neurons in the postmenopausal infundibular nucleus express estrogen receptor, kisspeptin and neurokinin B.
“These neurons express estrogen receptor, kisspeptin and neurokinin B (NKB) and the cellular hypertrophy is accompanied by increased neurokinin B and kisspeptin gene expression (Fig. 1) (Rance et al., 1990; Rance and Young, 1991; Rometo et al., 2007).”
From Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes (2013) · cites this paper as Rance et al., 1990
Cellular hypertrophy in the postmenopausal infundibular nucleus is accompanied by increased neurokinin B and kisspeptin gene expression.
“These neurons express estrogen receptor, kisspeptin and neurokinin B (NKB) and the cellular hypertrophy is accompanied by increased neurokinin B and kisspeptin gene expression (Fig. 1) (Rance et al., 1990; Rance and Young, 1991; Rometo et al., 2007).”
From Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes (2013) · cites this paper as Rance et al., 1990

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Authors: RANCE, N. E., McMULLEN, N. T., SMIALEK, J. E., PRICE, D. L., & YOUNG, W. S.
Affiliations: University of Maryland, Baltimore (US)
ORCID: RANCE, NAOMI E.
McMULLEN, NATHANIEL T.
YOUNG, W. SCOTT
Venue: The Journal of Clinical Endocrinology & Metabolism
Publisher: The Endocrine Society
Published: 1990-07
Volume: 71
Issue: 1
Pages: 79-85
ISSN: 0021-972X (ISSN-L)
1945-7197
DOI: 10.1210/jcem-71-1-79
OpenAlex: W2041695054
Cited by: 148
References: 44
Citations by year: 2026: 2 · 2025: 7 · 2024: 3 · 2023: 4 · 2022: 6 · 2021: 7 · 2020: 4 · 2019: 6 · 2018: 2 · 2017: 6 · 2016: 4 · 2015: 9 · 2014: 2 · 2013: 2 · 2012: 4
FWCI: 2.60
Type: journal article
Language: en
Open access: closed
Locations: The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5r35ag007914-03, 5t32ns007179-15)
National Institute on Aging (AG07914)
National Institute of Neurological Disorders and Stroke (NS10580, NS-07179)
Topics: Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
Keywords: postmenopause, neuronal hypertrophy, estrogen receptor mRNA, hypothalamus, arcuate nucleus, GnRH mRNA, oophorectomy, neuronal soma size, women
MeSH terms: Adult, Arcuate Nucleus of Hypothalamus, DNA, Feedback, Female, Gene Expression Regulation, Histocytochemistry, Humans, Hypertrophy, Hypothalamus, Menopause, Middle Aged, Neurons, Nucleic Acid Hybridization, Receptors, Estrogen, RNA, Messenger

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Postmenopausal hypertrophy of neurons expressing the estrogen receptor gene in the human hypothalamus

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