KNDy Neurons Modulate the Magnitude of the Steroid-Induced Luteinizing Hormone Surges in Ovariectomized Rats

Autor(es)

Helena, Cleyde V. ^{[1, 2]} ; Toporikova, Natalia ^[3] ; Kalil, Bruna ^[4] ; Stathopoulos, Andrea M. ^{[1, 5]} ; Pogrebna, Veronika V. ^[3] ; Carolino, Ruither O. ^[6] ; Anselmo-Franci, Janete A. ^[6] ; Bertram, Richard ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] Florida State Univ, Program Neurosci, Tallahassee, FL 32306 - USA

^[2] Florida State Univ, Dept Math, Tallahassee, FL 32306 - USA

^[3] Washington & Lee Univ, Dept Biol, Lexington, VA 24450 - USA

^[4] Univ Sao Paulo, Sch Med, Dept Physiol, BR-14040900 Ribeirao Preto, SP - Brazil

^[5] Florida State Univ, Dept Biol, Tallahassee, FL 32306 - USA

^[6] Univ Sao Paulo, Sch Dent, Dept Morphol Stomatol & Physiol, BR-14040900 Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Endocrinology; v. 156, n. 11, p. 4200-4213, NOV 2015.
• Citações Web of Science: 17

Resumo

Kisspeptin is the most potent stimulator of LH release. There are two kisspeptin neuronal populations in the rodent brain: in the anteroventral periventricular nucleus (AVPV) and in the arcuate nucleus. The arcuate neurons coexpress kisspeptin, neurokinin B, and dynorphin and are called KNDy neurons. Because estradiol increases kisspeptin expression in the AVPV whereas it inhibits KNDy neurons, AVPV and KNDy neurons have been postulated to mediate the positive and negative feedback effects of estradiol on LH secretion, respectively. Yet the role of KNDy neurons during the positive feedback is not clear. In this study, ovariectomized rats were microinjected bilaterally into the arcuate nucleus with a saporin-conjugated neurokinin B receptor agonist for targeted ablation of approximately 70% of KNDy neurons. In oil-treated animals, ablation of KNDy neurons impaired the rise in LH after ovariectomy and kisspeptin content in both populations. In estradiol-treated animals, KNDy ablation did not influence the negative feedback of steroids during the morning. Surprisingly, KNDy ablation increased the steroid-induced LH surges, accompanied by an increase of kisspeptin content in the AVPV. This increase seems to be due to lack of dynorphin input from KNDy neurons to the AVPV as the following: 1) microinjections of a dynorphin antagonist into the AVPV significantly increased the LH surge in estradiol-treated rats, similar to KNDy ablation, and 2) intra-AVPV microinjections of dynorphin in KNDy-ablated rats restored LH surge levels. Our results suggest that KNDy neurons provide inhibition to AVPV kisspeptin neurons through dynorphin and thus regulate the amplitude of the steroid-induced LH surges. (AU)

• Processo FAPESP: 11/51610-8 - Papel da neurotransmissao noradrenergica via kisspeptina na genese do pico de lh em ratas.
• Beneficiário: Janete Aparecida Anselmo Franci
• Modalidade de apoio: Auxílio à Pesquisa - Regular