Cited by 119Hypothalamic control of reproductive hormonesRegulation of Appetite and ObesityNeuroendocrine regulation and behavior

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Prolactin Regulates Kisspeptin Neurons in the Arcuate Nucleus to Suppress LH Secretion in Female Rats

Araujo-Lopes, Roberta, Crampton, Jessica R., Aquino, Nayara S.S., Miranda, Roberta M., Kokay, Ilona C., Reis, Adelina M., Franci, Celso R., Grattan, David R., Szawka, Raphael E.·2014·Endocrinology

DOI 10.1210/en.2013-1889

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Abstract

Prolactin (PRL) is known to suppress LH secretion. Kisspeptin neurons regulate LH secretion and express PRL receptors. We investigated whether PRL acts on kisspeptin neurons to suppress LH secretion in lactating (Lac) and virgin rats. Lac rats displayed high PRL secretion and reduced plasma LH and kisspeptin immunoreactivity in the arcuate nucleus (ARC). Bromocriptine-induced PRL blockade significantly increased ARC kisspeptin and plasma LH levels in Lac rats but did not restore them to the levels of non-Lac rats. Bromocriptine effects were prevented by the coadministration of ovine PRL (oPRL). Virgin ovariectomized (OVX) rats treated with either systemic or intracerebroventricular oPRL displayed reduction of kisspeptin expression in the ARC and plasma LH levels, and these effects were comparable with those of estradiol treatment in OVX rats. Conversely, estradiol-treated OVX rats displayed increased kisspeptin immunoreactivity in the anteroventral periventricular nucleus, whereas oPRL had no effect in this brain area. The expression of phosphorylated signal transducer and activator of transcription 5 was used to determine whether kisspeptin neurons in the ARC were responsive to PRL. Accordingly, intracerebroventricular oPRL induced expression of phosphorylated signal transducer and activator of transcription 5 in the great majority of ARC kisspeptin neurons in virgin and Lac rats. We provide here evidence that PRL acts on ARC neurons to inhibit kisspeptin expression in female rats. During lactation, PRL contributes to the inhibition of ARC kisspeptin. In OVX rats, high PRL levels suppress kisspeptin expression and reduce LH release. These findings suggest a pathway through which hyperprolactinemia may inhibit LH secretion and thereby cause infertility.

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Authors: Araujo-Lopes, R., Crampton, J. R., Aquino, N. S. S., Miranda, R. M., Kokay, I. C., Reis, A. M., Franci, C. R., Grattan, D. R., & Szawka, R. E.
Affiliations: University of Otago (NZ)
Universidade Federal de Minas Gerais (BR)
Universidade de São Paulo (BR)
ORCID: Aquino, Nayara S.S.
Miranda, Roberta M.
Reis, Adelina M.
Grattan, David R.
Szawka, Raphael E.
Venue: Endocrinology
Publisher: The Endocrine Society
Published: 2014-03
Volume: 155
Issue: 3
Pages: 1010-1020
ISSN: 0013-7227 (ISSN-L)
1945-7170
DOI: 10.1210/en.2013-1889
OpenAlex: W2111299253
Cited by: 119
References: 58
Citations by year: 2026: 2 · 2025: 7 · 2024: 9 · 2023: 6 · 2022: 15 · 2021: 10 · 2020: 15 · 2019: 11 · 2018: 7 · 2017: 9 · 2016: 10 · 2015: 11 · 2014: 6
FWCI: 14.57
Type: journal article
Language: en
Open access: closed
Locations: Endocrinology (publishedVersion)
PubMed (publishedVersion)
Funders: Pfizer
Topics: Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroendocrine regulation and behavior
Keywords: prolactin, kisspeptin neurons, arcuate nucleus, luteinizing hormone secretion, lactation, hyperprolactinemia, ovariectomy, estradiol, anteroventral periventricular nucleus, STAT5 phosphorylation, bromocriptine, prolactin receptor, female infertility, hypothalamic regulation of reproduction
MeSH terms: Animals, Arcuate Nucleus of Hypothalamus, Bromocriptine, Estradiol, Female, Hyperprolactinemia, Immunohistochemistry, Luteinizing Hormone, Neurons, Phosphorylation, Prolactin, Radioimmunoassay, Sheep, Rats, Sprague-Dawley, Rats, Wistar, STAT5 Transcription Factor, Rats, Kisspeptins

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Prolactin Regulates Kisspeptin Neurons in the Arcuate Nucleus to Suppress LH Secretion in Female Rats

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