Vasoactive intestinal peptide exerts an excitatory effect on hypothalamic kisspeptin neurons during estrogen negative feedback. (15th February 2022)

• Record Type: Journal Article
• Authors: Mansano, Naira da Silva; Paradela, Regina Silva; Bohlen, Tabata M.; Zanardi, Izabela M.; Chaves, Fernanda Machado; Silveira, Marina Augusto; Tavares, Mariana Rosolen; Donato, Jose; Frazao, Renata
• Is Part Of: Molecular and cellular endocrinology. Volume 542(2022)
• Publication Date: 2022-02-15
• Subjects: Kiss1 -- Hypothalamus -- VIP receptors -- Sex steroids; Endocrinology -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Endocrinology -- Periodicals; Hormones -- Periodicals; Endocrinologie -- Périodiques; Cytology; Endocrinology; Molecular biology; Periodicals; 573.4
• DOI: 10.1016/j.mce.2021.111532
• Languages: English
• ISSNs: 0303-7207

Abstract

Abstract: Hypothalamic kisspeptin neurons are the primary modulators of gonadotropin-releasing hormone (GnRH) neurons. It has been shown that circadian rhythms driven by the suprachiasmatic nucleus (SCN) contribute to GnRH secretion. Kisspeptin neurons are potential targets of SCN neurons due to reciprocal connections with the anteroventral periventricular and rostral periventricular nuclei (AVPV/PeN) and the arcuate nucleus of the hypothalamus (ARH). Vasoactive intestinal peptide (VIP), a notable SCN neurotransmitter, modulates GnRH secretion depending on serum estradiol levels, aging or time of the day. Considering that kisspeptin neurons may act as interneurons and mediate VIP's effects on the reproductive axis, we investigated the effects of VIP on hypothalamic kisspeptin neurons in female mice during estrogen negative feedback. Our findings indicate that VIP induces a TTX-independent depolarization of approximately 30% of AVPV/PeN kisspeptin neurons in gonad-intact (diestrus) and ovariectomized (OVX) mice. In the ARH, the percentage of kisspeptin neurons that were depolarized by VIP was even higher (approximately 90%). An intracerebroventricular infusion of VIP leds to an increased percentage of kisspeptin neurons expressing the phospho Ser133 cAMP-response-element-binding protein (pCREB) in the AVPV/PeN. On the other hand, pCREB expression in ARH kisspeptin neurons was similar between saline- and VIP-injected mice. Thus, VIP can recruit different signaling pathways to modulate AVPV/PeN or ARH kisspeptin neurons, resulting in distinct cellular responses. The expression of VIP receptors (VPACR) was upregulated in the AVPV/PeN, but not in the ARH, of OVX mice compared to mice on diestrus and estradiol-primed OVX mice. Our findings indicate that VIP directly influences distinct cellular aspects of the AVPV/PeN and ARH kisspeptin neurons during estrogen negative feedback, possibly to influence pulsatile LH secretion. Highlights: VIP directly depolarizes 30% of AVPV/PeN kisspeptin neurons in diestrus mice. VIP directly depolarizes approximately 90% of ARH kisspeptin neurons of diestrus females. Central VIP infusion increases pCREB levels only in AVPV/PeN kisspeptin neurons. VPACR expression is upregulated in the AVPV/PeN of OVX mice. VIP responsiveness in AVPV/PeN kisspeptin neurons is similar in diestrus and OVX mice.