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Vasopressin and Oxytocin Neurons of the Human Supraoptic and Paraventricular Nucleus; Size Changes in Relation to Age and Sex
Abstract
The hypothalamic supraoptic (SON) and paraventricular (PVN) nuclei consist of arginine vasopressin (AVP)- and oxytocin (OT)-synthesizing neurons that send projections to the neurohypophysis, whereas the PVN also projects to other brain areas. A growing body of evidence in animals suggests the presence of sex differences in the vasopressinergic and oxytocinergic systems. The present study was aimed at determining whether the sizes of AVP and OT neurons in the human SON and PVN show sex differences, as earlier studies demonstrated that a change in neuronal size is a sensitive parameter for activity. The minimal and maximal diameters were determined to estimate the volumes of cell somata and cell nuclei in AVP and OT neurons stained with an antibody against human glycoprotein-(22-39), a part of the AVP precursor, and a monoclonal anti-OT antibody in 15 men and 17 women ranging in age from 29-94 yr. The AVP neurons appeared to be larger in young men than in young women (< or =50 yr old). In elderly women (>50 yr old) AVP cell size considerably exceeded that in young women. In elderly men AVP neurons were larger than in young men and elderly women, although these differences were not significant. In addition, AVP cell size correlated positively with age in women but not in men. No significant differences were found in the AVP cell nucleus volumes among all four groups studied. Sex differences in the size of the PVN vasopressin neurons were pronounced at the left side (P = 0.048) and absent at the right side (P = 0.368), indicating the presence of functional lateralization in this nucleus. No difference was found in any morphometric parameter of OT neurons in the PVN among the 4 groups studied. Thus, our data demonstrate sex differences in the size of the AVP neurons, and thus in their function, that are age and probably also side dependent and the absence of such changes in OT neurons in the PVN. These data provide a basis for the reported higher AVP plasma levels in men compared to women.
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In the citing paper
“women reportedly have larger PVN AVP neurons than men”
From Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity (2017) · cites this paper as Ishunina & Swaab, 1999
In the citing paper
“There are also fundamental sex-dependent brain differences between males and females, e.g., the size of vasopressin (AVP) neurons (271).”
From Epigenetic Modifications in Stress Response Genes Associated With Childhood Trauma (2019) · cites this paper as [271]
In the citing paper
“Menstrual cycle hormones affect fluid dynamics by altering capillary permeability, vasomotor function, fluid regulatory hormone release, and plasma osmolality [265].”
From International society of sports nutrition position stand: nutritional concerns of the female athlete (2023) · cites this paper as [265]
In the citing paper
“Sex differences have also been found in AVP/AVT neurons in the PVN in mammals, including humans (Ishunina and Swaab, 1999), and the preoptic area in non-mammalian vertebrates, especially in fish (e.g. Grober and Sunobe, 1996; Semsar and Godwin, 2003).”
From Sexual differentiation of central vasopressin and vasotocin systems in vertebrates: different mechanisms, similar endpoints (2006) · cites this paper as Ishunina and Swaab, 1999
In the citing paper
“Estrogen receptors are present in the hypothalamic nuclei of animals known to produce AVP (10,21), and a number of studies have demonstrated sex differences in the AVP neuron activity and size in these nuclei (12).”
From Sex Hormone Effects on Body Fluid Regulation (2008) · cites this paper as [12]
In the citing paper
“However, no extrahypothalamic OT neurons were found in either Macaca or Homo (Caffé et al., 1989; Ishunina and Swaab, 1999), but OT-ir neurons were found in the BNST and meA of Callithrix (Wang et al., 1997a, 1997b).”
From Neuropeptide diversity and the regulation of social behavior in New World primates (2016) · cites this paper as Ishunina and Swaab, 1999
In the citing paper
“As expected, OT- and AVP-containing neurons have been identified in the PVN and SON in Callithrix (Wang et al., 1997a, 1997b), Macaca (Caffé et al., 1989), and Homo (Ishunina and Swaab, 1999).”
From Neuropeptide diversity and the regulation of social behavior in New World primates (2016) · cites this paper as Ishunina and Swaab, 1999
In the citing paper
“AVP-ir neurons are found in the BNST in these genera (Caffé et al., 1989; Fliers et al., 1986; Ishunina and Swaab, 1999; Wang et al., 1997a).”
From Neuropeptide diversity and the regulation of social behavior in New World primates (2016) · cites this paper as Ishunina and Swaab, 1999
In the citing paper
“In Homo, males and females do no differ in the number or size of OT-ir neurons in the neurohypophyseal tract (Fliers et al., 1985; Ishunina and Swaab, 1999; Wierda et al., 1991).”
From Neuropeptide diversity and the regulation of social behavior in New World primates (2016) · cites this paper as Ishunina and Swaab, 1999
In the citing paper
“Interestingly, there is a sex difference in the size of AVP-ir neurons in Homo under 50 years of age, with men having significantly larger AVP neurons than women (Ishunina and Swaab, 1999).”
From Neuropeptide diversity and the regulation of social behavior in New World primates (2016) · cites this paper as Ishunina and Swaab, 1999
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Metadata
- Authors
- Ishunina, T. A., & Swaab, D. F.
- Affiliations
- Kursk State Medical University (RU)
- Corresponding author
- Swaab, Dick F.
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 1999-12
- Volume
- 84
- Issue
- 12
- Pages
- 4637-4644
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2168302875
- Cited by
- 132
- References
- 67
- Citations by year
- 2026: 6 · 2025: 4 · 2024: 6 · 2023: 11 · 2022: 3 · 2021: 8 · 2020: 3 · 2019: 10 · 2018: 8 · 2017: 4 · 2016: 4 · 2015: 5 · 2014: 4 · 2013: 6 · 2012: 7
- FWCI
- 9.64
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroendocrine regulation and behavior
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- arginine vasopressin neurons, oxytocin neurons, supraoptic nucleus, paraventricular nucleus, hypothalamus, neuron size, sex differences, age differences, laterality, neurohypophysis
- MeSH terms
- Adult, Aged, Aged, 80 and over, Aging, Female, Humans, Hypothalamus, Immunohistochemistry, Male, Middle Aged, Neurons, Oxytocin, Paraventricular Hypothalamic Nucleus, Supraoptic Nucleus, Vasopressins, Cell Size
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