Gonadotropin Stimulation Increases the Expression of Angiotensin-(1–7) and Mas Receptor in the Rat Ovary
Open accessAbstract
We have previously shown the presence of immunoreactive angiotensin-(1-7) [Ang-(1-7)] in rat ovary homogenate and its stimulatory effect on estradiol and progesterone production in vitro. In the current study, we investigated the presence and cellular distribution of Ang-(1-7) and the Mas receptor, the expression of Mas and angiotensin-converting enzyme 2 (ACE2) messenger RNA (mRNA), and the enzymatic activity in the rat ovary following gonadotropin stimulation in vivo. Immature female Wistar rats (25 days old) were injected subcutaneously (SC) with equine chorionic gonadotropin (eCG, 20 IU in 0.2 mL) or vehicle 48 hours before euthanasia. Tissue distributions of Ang-(1-7), Mas receptor, and ACE2 were evaluated by immunohistochemistry, along with angiotensin II (Ang II) localization, while the mRNA expression levels of Mas receptor and ACE2 were evaluated by real-time polymerase chain reaction (PCR). In addition, we determined the activity of neutral endopeptidase (NEP), prolyl endopeptidase (PEP), and ACE by fluorometric assays. After eCG treatment, we found strong immunoreactivity for Ang-(1-7) and Mas primarily in the theca-interstitial cells, while Ang II appeared in the granulosa but not in the thecal layer. Equine chorionic gonadotropin treatment increased Mas and ACE2 mRNA expression compared with control animals (3.3- and 2.1-fold increase, respectively; P < .05). Angiotensin-converting enzyme and NEP activities were lower, while PEP activity was higher in the eCG-treated rats (P < .05). These data show gonadotropin-induced changes in the ovarian expression of Ang-(1-7), Mas receptor, and ACE2. These findings suggest that the renin-angiotensin system (RAS) branch formed by ACE2/Ang-(1-7)/Mas, fully expressed in the rat ovary and regulated by gonadotropic hormones, could play a role in the ovarian physiology.
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Gonadotropin mediates the activation of ovarian RAS, and local RAS may be an intermediate for gonadotropin work in ovary.
“This is consistent with the results of previous studies, which clarify that gonadotropin mediates the activation of ovarian RAS [64, 66], and local RAS may be an intermediate for the gonadotropin work in ovary [67].”
From Transplantation of human umbilical cord-derived mesenchymal stem cells improves age-related ovarian functional decline via regulating the local renin–angiotensin system on inflammation and oxidative stress (2024) · cites this paper as [66]
The paper’s summary of findings (p. 1165) reports that gonadotropin treatment changed components of the ovarian RAS in rats and suggests that this RAS branch could play a role in ovarian physiology. It does not establish or explicitly propose the more specific claim attached to this citation: that local RAS mediates gonadotropin’s effects in the ovary. (LLM, conf=0.82)
Experimental — accuracy not yet measuredAng(1-7) through MasR has effects on the establishment of dominant follicles, response to gonadotropin, and the regulation of local steroid production and ovulation.
“Animal models provide more evidence that Ang(1–7) through MasR has effects on the establishment of dominant follicles [65], response to gonadotropin [66, 67], the regulation of local steroid production and ovulation [68–70].”
From Transplantation of human umbilical cord-derived mesenchymal stem cells improves age-related ovarian functional decline via regulating the local renin–angiotensin system on inflammation and oxidative stress (2024) · cites this paper as [66]
The opening study summary reports that gonadotropin treatment increased ovarian Mas and ACE2 expression in rats. This connects the Ang-(1–7)/Mas pathway to gonadotropin stimulation, but it does not show that the pathway affects the ovary’s response to gonadotropin; the demonstrated direction is the reverse. The other outcomes in the citing sentence are attached to different citations. (LLM, conf=0.85)
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Research works printed but not linked: 42
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- Authors
- Pereira, V. M., Reis, F. M., Santos, R. A. S., Cassali, G. D., Santos, S. H. S., Honorato-Sampaio, K., & dos Reis, A. M.
- Affiliations
- Universidade Federal de Minas Gerais (BR)
- ORCID
- Venue
- Reproductive Sciences
- Published
- 2009-12
- Volume
- 16
- Issue
- 12
- Pages
- 1165-1174
- ISSN
- 1933-7191 (ISSN-L)
- 1933-7205
- PMC
- PMC7101720
- OpenAlex
- W2119833001
- Cited by
- 88
- References
- 46
- Citations by year
- 2025: 2 · 2024: 9 · 2023: 7 · 2022: 9 · 2021: 11 · 2020: 17 · 2019: 3 · 2018: 4 · 2017: 2 · 2016: 2 · 2015: 2 · 2014: 2 · 2013: 5 · 2012: 6
- FWCI
- 2.81
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Reproductive Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
- Keywords
- angiotensin-(1-7), Mas receptor, angiotensin-converting enzyme 2, renin-angiotensin system, gonadotropin stimulation, equine chorionic gonadotropin, ovary, theca-interstitial cells, granulosa cells, angiotensin II, neutral endopeptidase, prolyl endopeptidase, ACE activity, ovarian physiology, gene expression
- MeSH terms
- Prolyl Oligopeptidases, Angiotensin-Converting Enzyme 2, Proto-Oncogene Mas, Angiotensin I, Angiotensin II, Animals, Female, Gonadotropins, Equine, Immunohistochemistry, Injections, Subcutaneous, Peptidyl-Dipeptidase A, Ovary, Peptide Fragments, Proto-Oncogene Proteins, RNA, Messenger, Serine Endopeptidases, Spectrometry, Fluorescence, Superovulation, Neprilysin, Up-Regulation, Polymerase Chain Reaction, Rats, Wistar, Receptors, G-Protein-Coupled, Rats
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