Effects of ovariectomy on the neuroendocrine axes regulating reproduction and energy balance in young cynomolgus macaques
Abstract
Degeneration of the ovary in middle-aged women results in castrate levels of ovarian steroids and increased gonadotropin secretion from the anterior pituitary gland. Ageing in women is also accompanied by significant changes in energy homeostasis. We have observed alterations in hypothalamic morphology and gene expression in older women, including hypertrophy and increased gene expression of neurokinin B (NKB) neurones, elevated levels of gonadotropin releasing-hormone (GnRH) mRNA and decreased numbers of neurones expressing pro-opiomelanocortin (POMC) mRNA. To determine if loss of ovarian steroids could produce comparable changes in gene expression in young primates, we measured the effects of ovariectomy on NKB, GnRH and POMC gene expression in young cynomolgus monkeys. We also measured serum leptin and body weight to examine the consequences of ovariectomy on energy balance. NKB neurones in the infundibular nucleus of ovariectomized monkeys were larger, more numerous and displayed increased levels of NKB mRNA compared to those of intact controls. Moreover, ovariectomy increased the number of neurones expressing GnRH gene transcripts and elevated serum luteinizing hormone. By contrast, several parameters related to energy balance, including POMC gene expression, serum leptin and body weights, were unchanged by ovariectomy. Thus, the rise in NKB and GnRH gene expression in older women was simulated by ovariectomy in monkeys, but the changes in POMC gene expression and energy balance were not. This study provides strong support for the hypothesis that ovarian failure contributes to the increased NKB and GnRH gene expression observed in postmenopausal women.
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The hypertrophy and increased kisspeptin and NKB gene expression in postmenopausal women are secondary to estrogen withdrawal.
“The hypertrophy and increased kisspeptin and NKB gene expression in postmenopausal women are secondary to estrogen withdrawal, because these changes are induced by ovariectomy (Fig. 2) and reversed by estrogen replacement of young cynomolgus monkeys (Abel et al., 1999; Rometo et al., 2007; Sandoval-Guzmán et al., 2004).”
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 Sandoval-Guzmán et al., 2004
Ovariectomy induces neuronal hypertrophy and increased NKB and kisspeptin gene expression in young cynomolgus monkeys, and estrogen replacement reverses these changes.
“The hypertrophy and increased kisspeptin and NKB gene expression in postmenopausal women are secondary to estrogen withdrawal, because these changes are induced by ovariectomy (Fig. 2) and reversed by estrogen replacement of young cynomolgus monkeys (Abel et al., 1999; Rometo et al., 2007; Sandoval-Guzmán et al., 2004).”
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 Sandoval-Guzmán et al., 2004
Ovariectomy produces neuronal hypertrophy and increased NKB and kisspeptin gene expression in the arcuate nucleus of young monkeys, identical to that seen in postmenopausal women.
“Ovariectomy produces neuronal hypertrophy and increased NKB and kisspeptin gene expression in the arcuate nucleus of young monkeys, and these findings are identical to that seen in postmenopausal women (Fig. 2) (Alçin et al., 2013; Rometo et al., 2007; Sandoval-Guzmán et al., 2004).”
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 Sandoval-Guzmán et al., 2004
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- Authors
- Sandoval‐Guzmán, T., Stalcup, S. T., Krajewski, S. J., Voytko, M. L., & Rance, N. E.
- Affiliations
- University of Arizona (US)
- Wake Forest University Health Sciences (US)
- Corresponding author
- Rance, N. E.
- Venue
- Journal of Neuroendocrinology
- Publisher
- Wiley
- Published
- 2004-02
- Volume
- 16
- Issue
- 2
- Pages
- 146-153
- ISSN
- 0953-8194 (ISSN-L)
- 1365-2826
- OpenAlex
- W2055613172
- Cited by
- 60
- References
- 60
- Citations by year
- 2025: 2 · 2024: 1 · 2023: 2 · 2022: 3 · 2021: 1 · 2020: 2 · 2019: 1 · 2018: 6 · 2017: 2 · 2016: 2 · 2015: 4 · 2014: 5 · 2013: 1 · 2012: 6
- FWCI
- 2.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Oregon National Primate Research Center
- Wake Forest School of Medicine
- National Institute on Aging (AG09214)
- NIH Clinical Center
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
- Keywords
- ovariectomy, ovarian failure, neurokinin B, gonadotropin-releasing hormone, proopiomelanocortin, hypothalamic gene expression, arcuate nucleus, luteinizing hormone, leptin, energy balance, reproductive axis, postmenopausal women, Macaca fascicularis
- MeSH terms
- Animals, Arcuate Nucleus of Hypothalamus, Body Weight, Disease Models, Animal, Energy Metabolism, Female, Gene Expression Regulation, Hypertrophy, Gonadotropin-Releasing Hormone, Macaca fascicularis, Menopause, Neurons, Neurosecretory Systems, Ovariectomy, Ovary, Pro-Opiomelanocortin, Random Allocation, RNA, Messenger, Neurokinin B, Leptin
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