Prolactin regulates kisspeptin neurons in the arcuate nucleus to suppress LH secretion in female rats.
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.
Departamento de Fisiologia e Biofísica (R.A.-L., N.S.S.A., R.M.M., A.M.R., R.E.S.), Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Minas Gerais, Brazil; Centre for Neuroendocrinology and Department of Anatomy (J.R.C., I.C.K., D.R.G.), University of Otago, Dunedin, 9054, New Zealand; and Departamento de Fisiologia (C.R.F.), Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto 14049-900, São Paulo, Brazil.
Roberta
R
Araujo-Lopes
Jessica R
JR
Crampton
Nayara S S
NS
Aquino
Roberta M
RM
Miranda
Ilona C
IC
Kokay
Adelina M
AM
Reis
Celso R
CR
Franci
David R
DR
Grattan
Raphael E
RE
Szawka
D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism*; D001971:Bromocriptine / Q000737:chemistry; D004958:Estradiol / Q000378:metabolism; D005260:Female; D006966:Hyperprolactinemia / Q000378:metabolism; D007150:Immunohistochemistry; D059648:Kisspeptins / Q000378:metabolism*; D007986:Luteinizing Hormone / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D010766:Phosphorylation; D011388:Prolactin / Q000378:metabolism*; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D050799:STAT5 Transcription Factor / Q000378:metabolism; D012756:Sheep
D059648:Kisspeptins; D050799:STAT5 Transcription Factor; D001971:Bromocriptine; D004958:Estradiol; D011388:Prolactin; D007986:Luteinizing Hormone