Control of hypothalamic KNDy neurons during the menstrual cycle of the rhesus monkey

• Grant number: 13/03596-1
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: August 01, 2013
• End date: July 31, 2014
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Janete Aparecida Anselmo Franci
• Grantee: Bruna Kalil Cutti
• Supervisor: Tony M. Plant
• Host Institution: Faculdade de Odontologia de Ribeirão Preto (FORP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: University of Pittsburgh (Pitt), United States
• Associated to the scholarship: 10/12642-9 - "Noradrenergic modulation of kisspeptin/GnRH systems and clock genes expression in the control of the estradiol induced LH surge in ovariectomized rats", BP.DR

Abstract

The hypothalamic gonadotropin-releasing hormone (GnRH) pulse generator is the key element that governs ovarian ciclicity in mammals. The GnRH pulse generator, located within the medial basal hypothalamus (MBH) to the region of the arcuate nucleus (ARC), governs intermittent GnRH discharges into the pituitary portal circulation and thereby regulates pulsatile luteinizing hormone (LH) release into the peripheral circulation. Recently, it has been shown that a subset of neurons in the ARC nucleus which express kisspeptin, neurokinin B and dynorphin, namely KNDy neurons, are critical elements comprising the GnRH pulse generator. Moreover, earlier studies have shown that several other neurotransmitters/neuropeptide systems modulate positively or negatively the pulsatile activity of GnRH neurons in many species. However, the attribution of the relative importance to these various inputs in regulating GnRH pulsatility has been one of the major challenges of reproductive physiology. We hypothesize that KNDy neurons may represent a final common pathway by which the internal signals (mainly from the ovaries) and environmental cues are integrated and relayed to the GnRH neuronal network. In higher primates, noradrenergic, glutamatergic, gabaergic and neuropeptide Y systems have shown to be major central regulators of GnRH pulsatility and are likely candidates to relay such information to the KNDy neurons. Nevertheless, the relationship among KNDy neurons and these endogenous GnRH modulators remains unexplored and worthy for investigation. In the present study we propose to address this question by a morphological examination of receptor expression by KNDy neurons in the MBH of female rhesus monkey and evaluate whether such expressions varies across the menstrual cycle using immunohistochemistry and in situ hybridization techniques. The candidate receptors are alpha1 adrenergic, GABA(A), NMDA and Y1 receptors subtypes as these receptors signaling have shown to strongly influence GnRH pulsatility. The characterization of KNDy neurons receptors phenotype represents an opportunity to elucidate, in some extent, the integration process of the multifactorial regulation of GnRH pulsatility, which is essential for the proper functioning of the reproductive axis. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

KALIL, BRUNA; RAMASWAMY, SURESH; PLANT, TONY M.. The Distribution of Substance P and Kisspeptin in the Mediobasal Hypothalamus of the Male Rhesus Monkey and a Comparison of Intravenous Administration of These Peptides to Release GnRH as Reflected by LH Secretion. Neuroendocrinology, v. 103, n. 6, p. 711-723, 2016. (13/03596-1)

TRUJILLO, MARCELA VARGAS; KALIL, BRUNA; RAMASWAMY, SURESH; PLANT, TONY M.. Estradiol Upregulates Kisspeptin Expression in the Preoptic Area of both the Male and Female Rhesus Monkey (Macaca mulatta) : Implications for the Hypothalamic Control of Ovulation in Highly Evolved Primates. Neuroendocrinology, v. 105, n. 1, p. 77-89, 2017. (13/03596-1)