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Estrogen Receptors Alpha and Beta in POA-AHA Region Regulate Asymmetrically Ovulation

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Abstract

We examined the role of the estrogen receptors alpha (ERα) and beta (ERβ) in of the preoptic-anterior hypothalamic area (POA-AHA) in the regulation of ovulation in rats. The number of ERα- and ERβ-immunoreactive (-ir) cells was determined at 09:00, 13:00, and 17:00 h of each stage of the estrous cycle in intact rats. Additionally, the effects of blocking ERα and ERβ on ovulation rate at 09:00 h on diestrus-2 or proestrus day through the microinjection of methyl-piperidino-pyrazole (MPP) or cyclofenil in either side of POA-AHA were evaluated. The number of ERα-ir and ERβ-ir cells in POA-AHA varied in each phase of estrous cycle. Either MPP or cyclofenil in the right side of POA-AHA on diestrus-2 day reduced the ovulation rate, while at proestrus day it was decreased in rats treated in either side with MPP, and in those treated with cyclofenil in the left side. MPP or cyclofenil produced a decrease in the surge of luteinizing hormone levels (LH) and an increase in progesterone and follicle stimulating hormone (FSH). Replacement with synthetic luteinizing hormone-releasing hormone in non-ovulating rats treated with MPP or cyclofenil restored ovulation. These results suggest that activation of estrogen receptors on the morning of diestrus-2 and proestrus day asymmetrically regulates ovulation and appropriately regulates the secretion of FSH and progesterone in the morning and afternoon of proestrus day. This ensures that both, the preovulatory secretion of LH and ovulation, occur at the right time.

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Abbreviations

POA-AHA:

Preoptic and hypothalamic area

LH:

Luteinizing hormone

FSH:

Follicle stimulating hormone

GnRH:

Gonadotropin-releasing hormone

P4 :

Progesterone

E2 :

E2

ERα:

Estrogen receptors alpha

ERβ:

Beta

-ir:

Immunoreactive cells

MPP:

Methyl-piperidino-pyrazole

SERM:

Selective estrogen receptor modulator

ELISA:

Enzyme-linked immunoassay

RIA:

Radioimmunoassay

LHRH-Gly-OH:

Synthetic LH-Releasing Hormone

GABA:

Gamma aminobutyric acid

PRL:

Prolactin

PVN:

Paraventricular nucleus

MPA:

Medial preoptic area

MPOL:

Lateral part of medial preoptic nucleus

VMPO:

Ventromedial preoptic nucleus

PE:

Periventricular nucleus

3V:

Third ventricle

AVPe:

Anteroventral periventricular nucleus

ox:

Optic chiasm

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Acknowledgements

We thank to Facultad de Estudios Superiores, Zaragoza from UNAM at Mexico City by the access to the facilities used to perform this study and Michael Martínez-Mayo for his technical assistance.

Funding

This study was funded by UNAM-DGAPA-PAPIIT (grant number: IN214508-3 and IN-21005319), and CONACYT (grant number: 81898). Author Cruz ME has received research grants from UNAM-DGAPA-PAPIIT and CONACYT.

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MEC designed the experiments; MEC, IAC, RGJ, and RDC wrote the manuscript. IAC, MGL, and RLO performed the immunohistochemical analysis; RCh and CM quantified the concentrations of hormones; MEC, AF, IAC, RGJ, and RDC participated in the analysis and discussion of the results. All authors read and approved the final version of the manuscript.

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Correspondence to Isabel Arrieta-Cruz or María-Esther Cruz.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All experiments were performed in strict accordance with the Mexican Law of Animal Treatment and Protection Guidelines and the specifications of the Mexican Official Standard NOM-062-ZOO-1999. The Institutional Committee of the Facultad de Estudios Superiores Zaragoza, Universidad Nacional Autónoma de México approved the experimental protocols (FES/DEPUCI/236/14). All efforts were made to minimize the number of animals used and their suffering.

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Arrieta-Cruz, I., Librado-Osorio, R., Flores, A. et al. Estrogen Receptors Alpha and Beta in POA-AHA Region Regulate Asymmetrically Ovulation. Cell Mol Neurobiol 39, 1139–1149 (2019). https://doi.org/10.1007/s10571-019-00708-1

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