Neurotensin: a neuropeptide induced by hCG in the human and rat ovary during the periovulatory period

Al-Alem, Linah; Puttabyatappa, Muraly; Shrestha, Ketan; Choi, Yohan; Rosewell, Kathy; Brännström, Mats; Akin, James W.; Jo, Misung; Duffy, Diane M.; Curry, Thomas E.

doi:10.1093/biolre/ioab036

Cited by 7 publications

(25 citation statements)

References 52 publications

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“…The presence of receptors within the oocyte suggests a paracrine role for estrogens in its maturation process or an inducing role for other directly involved factors, such as neurotensin. Documentation on the role of this peptide in the ovary is very scarce, and only recently has its expression during the periovulatory period been described in human and rat ovaries with hCG hormone-induced expression [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

“…We also showed that these NTS-ir pituitary cells are also ERα-ir and that the distribution pattern of NTS-ir cells in the pituitary gland partially depends on gonadal function [ 6 , 20 , 21 , 22 , 23 ]. Recent studies using experimental models have confirmed NTS expression in gonads [ 24 , 25 ]. These authors show that granulosa cells are likely the primary or only source of NTS in the ovulatory follicle, although it has also been put forward as a paracrine mediator of ovulation [ 25 ].…”

Section: Introductionmentioning

confidence: 99%

“…The hormonal changes the female rat undergoes during the cycle involve important changes in the expression of NTS and its receptors [ 6 ], as well as in the presence of ERs [ 22 ]. The presence of NTS in ovarian, granulosa, and stromal cells has been demonstrated experimentally in humans and rats [ 24 ]. As we have previously shown, the expression of NTS in the gonadal axis is induced by endogenous estrogens [ 6 , 21 ], but the action of exogenous estrogens on this expression is unknown [ 62 , 63 ].…”

Section: Introductionmentioning

confidence: 99%

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NTS, NTSR1 and ERs in the Pituitary–Gonadal Axis of Cycling and Postnatal Female Rats after BPA Treatment

González‐Gómez

Reyes

Damas-Hernández

et al. 2023

IJMS

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The neuropeptide neurotensin (NTS) is involved in regulating the reproductive axis and is expressed at each level of this axis (hypothalamus–pituitary–gonads). This dependence on estrogen levels has been widely demonstrated in the hypothalamus and pituitary. We focused on confirming the relationship of NTS with estrogens and the gonadal axis, using a particularly important environmental estrogenic molecule, bisphenol-A (BPA). Based on the experimental models or in vitro cell studies, it has been shown that BPA can negatively affect reproductive function. We studied for the first time the action of an exogenous estrogenic substance on the expression of NTS and estrogen receptors in the pituitary-gonadal axis during prolonged in vivo exposure. The exposure to BPA at 0.5 and 2 mg/kg body weight per day during gestation and lactation was monitored through indirect immunohistochemical procedures applied to the pituitary and ovary sections. Our results demonstrate that BPA induces alterations in the reproductive axis of the offspring, mainly after the first postnatal week. The rat pups exposed to BPA exhibited accelerated sexual maturation to puberty. There was no effect on the number of rats born per litter, although the fewer primordial follicles suggest a shorter fertile life.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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NTS, NTSR1 and ERs in the Pituitary–Gonadal Axis of Cycling and Postnatal Female Rats after BPA Treatment

González‐Gómez

Reyes

Damas-Hernández

et al. 2023

IJMS

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“…However, few studies elaborated on the role of neurotransmitters and neuropeptides during ovulation. The neuropeptide neurotensin (NT) was first identified in bovine hypothalamus (Carraway & Leeman, 1973) and was reported to be expressed in other species and tissues, including humans and rat ovaries during the periovulatory period (Al-Alem et al, 2021). Soon several reports demonstrated role for NT in multiple aspects of ovarian function and sperm capacitation (Reinecke, 1987;Dissen et al, 1996;Hiradate et al, 2014;Cerny et al, 2015;Sakumoto et al, 2015;Umezu et al, 2016).…”

Section: Neuronal Signaling In Oocyte Maturationmentioning

confidence: 99%

Neurotransmitters, neuropeptides and calcium in oocyte maturation and early development

Alhajeri

Alkhanjari

Hodeify

et al. 2022

Front. Cell Dev. Biol.

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A primary reason behind the high level of complexity we embody as multicellular organisms is a highly complex intracellular and intercellular communication system. As a result, the activities of multiple cell types and tissues can be modulated resulting in a specific physiological function. One of the key players in this communication process is extracellular signaling molecules that can act in autocrine, paracrine, and endocrine fashion to regulate distinct physiological responses. Neurotransmitters and neuropeptides are signaling molecules that renders long-range communication possible. In normal conditions, neurotransmitters are involved in normal responses such as development and normal physiological aspects; however, the dysregulation of neurotransmitters mediated signaling has been associated with several pathologies such as neurodegenerative, neurological, psychiatric disorders, and other pathologies. One of the interesting topics that is not yet fully explored is the connection between neuronal signaling and physiological changes during oocyte maturation and fertilization. Knowing the importance of Ca2+ signaling in these reproductive processes, our objective in this review is to highlight the link between the neuronal signals and the intracellular changes in calcium during oocyte maturation and embryogenesis. Calcium (Ca2+) is a ubiquitous intracellular mediator involved in various cellular functions such as releasing neurotransmitters from neurons, contraction of muscle cells, fertilization, and cell differentiation and morphogenesis. The multiple roles played by this ion in mediating signals can be primarily explained by its spatiotemporal dynamics that are kept tightly checked by mechanisms that control its entry through plasma membrane and its storage on intracellular stores. Given the large electrochemical gradient of the ion across the plasma membrane and intracellular stores, signals that can modulate Ca2+ entry channels or Ca2+ receptors in the stores will cause Ca2+ to be elevated in the cytosol and consequently activating downstream Ca2+-responsive proteins resulting in specific cellular responses. This review aims to provide an overview of the reported neurotransmitters and neuropeptides that participate in early stages of development and their association with Ca2+ signaling.

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“…1 Recent studies have identified neurotensin (NTS) as a paracrine mediator of ovulation. [3][4][5] This 13-amino acid peptide is produced primarily by the granulosa cells in response to the LH surge and is transiently but highly upregulated around the time of ovulation in the human, monkey, rat, and mouse ovary. [3][4][5] NTS exerts its effect directly on ovarian endothelial cells.…”

Section: Introductionmentioning

confidence: 99%

Neurotensin modulates ovarian vascular permeability via adherens junctions

Pearson,

Shrestha,

Curry

et al. 2024

The FASEB Journal

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Neurotensin (NTS) is a 13‐amino acid peptide which is highly expressed in the mammalian ovary in response to the luteinizing hormone surge. Antibody neutralization of NTS in the ovulatory follicle of the cynomolgus macaque impairs ovulation and induces follicular vascular dysregulation, with excessive pooling of red blood cells in the follicle antrum. We hypothesize that NTS is an essential intrafollicular regulator of vascular permeability. In the present study, follicle injection of the NTS receptor antagonist SR142948 also resulted in vascular dysregulation. To measure vascular permeability changes in vitro, primary macaque ovarian microvascular endothelial cells (mOMECs) were enriched from follicle aspirates and studied in vitro. When treated with NTS, permeability of mOMECs decreased. RNA sequencing (RNA‐Seq) of mOMECs revealed high mRNA expression of the permeability‐regulating adherens junction proteins N‐cadherin (CDH2) and K‐cadherin (CDH6). Immunofluorescent detection of CDH2 and CDH6 confirmed expression and localized these cadherins to the cell–cell boundaries, consistent with function as components of adherens junctions. mOMECs did not express detectable levels of the typical vascular endothelial cadherin, VE‐cadherin (CDH5) as determined by RNA‐Seq, qPCR, western blot, and immunofluorescence. Knockdown of CDH2 or CDH6 via siRNA abrogated the NTS effect on mOMEC permeability. Collectively, these data suggest that NTS plays an ovulation‐critical role in vascular permeability maintenance, and that CDH2 and CDH6 are involved in the permeability modulating effect of NTS on the ovarian microvasculature. NTS can be added to a growing number of angiogenic regulators which are critical for successful ovulation.

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Neurotensin: a neuropeptide induced by hCG in the human and rat ovary during the periovulatory period

Cited by 7 publications

References 52 publications

NTS, NTSR1 and ERs in the Pituitary–Gonadal Axis of Cycling and Postnatal Female Rats after BPA Treatment

NTS, NTSR1 and ERs in the Pituitary–Gonadal Axis of Cycling and Postnatal Female Rats after BPA Treatment

Neurotransmitters, neuropeptides and calcium in oocyte maturation and early development

Neurotensin modulates ovarian vascular permeability via adherens junctions

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