title: α-Estrogen and Progesterone Receptors Modulate Kisspeptin Effects on Prolactin: Role in Estradiol-Induced Prolactin Surge in Female Rats.
abstract: Kisspeptin (Kp) regulates prolactin (PRL) in an estradiol-dependent manner. We investigated the interaction between ovarian steroid receptors and Kp in the control of PRL secretion. Intracerebroventricular injections of Kp-10 or Kp-234 were performed in ovariectomized (OVX) rats under different hormonal treatments. Kp-10 increased PRL release and decreased 3,4-dihydroxyphenylacetic acid levels in the median eminence (ME) of OVX rats treated with estradiol (OVX+E), which was prevented by tamoxifen. Whereas these effects of Kp-10 were absent in OVX rats, they were replicated in OVX rats treated with selective agonist of estrogen receptor (ER)α, propylpyrazole triol, but not of ERβ, diarylpropionitrile. Furthermore, the Kp-10-induced increase in PRL was two times higher in OVX+E rats also treated with progesterone (OVX+EP), which was associated with a reduced expression of both tyrosine hydroxylase (TH) and Ser40-phosphorylated TH in the ME. Kp-10 also reduced dopamine levels in the ME of OVX+EP rats, an effect blocked by the progesterone receptor (PR) antagonist RU486. We also determined the effect of Kp antagonism with Kp-234 on the estradiol-induced surges of PRL and luteinizing hormone (LH), using tail-tip blood sampling combined with ultrasensitive enzyme-linked immunosorbent assay. Kp-234 impaired the early phase of the PRL surge and prevented the LH surge in OVX+E rats. Thus, we provide evidence that Kp stimulation of PRL release requires ERα and is potentiated by progesterone via PR activation. Moreover, alongside its essential role in the LH surge, Kp seems to play a role in the peak phase of the estradiol-induced PRL surge.
authors.affiliation: Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, MG, Brazil.
authors.forename: Nayara S S
authors.initials: NSS
authors.lastname: Aquino
authors.affiliation: Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, MG, Brazil.
authors.forename: Roberta
authors.initials: R
authors.lastname: Araujo-Lopes
authors.affiliation: Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, MG, Brazil.
authors.forename: Patricia C
authors.initials: PC
authors.lastname: Henriques
authors.affiliation: Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, MG, Brazil.
authors.forename: Felipe E F
authors.initials: FEF
authors.lastname: Lopes
authors.affiliation: Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, MG, Brazil.
authors.forename: Daniela O
authors.initials: DO
authors.lastname: Gusmao
authors.affiliation: Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, MG, Brazil.
authors.forename: Candido C
authors.initials: CC
authors.lastname: Coimbra
authors.affiliation: Departamento de Fisiologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto 14049-900, São Paulo, Brazil.
authors.forename: Celso R
authors.initials: CR
authors.lastname: Franci
authors.affiliation: Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, MG, Brazil.
authors.forename: Adelina M
authors.initials: AM
authors.lastname: Reis
authors.affiliation: Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, MG, Brazil.
authors.forename: Raphael E
authors.initials: RE
authors.lastname: Szawka
mesh_terms: D000818:Animals; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000502:physiology*; D005260:Female; D059648:Kisspeptins / Q000494:pharmacology*; D010052:Ovariectomy; D011388:Prolactin / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011980:Receptors, Progesterone / Q000502:physiology*
chemical_list: D047628:Estrogen Receptor alpha; D059648:Kisspeptins; D011980:Receptors, Progesterone; D004958:Estradiol; D011388:Prolactin