"Noradrenergic modulation of kisspeptin/GnRH systems and clock genes expression in the control of the estradiol induced LH surge in ovariectomized rats"

• Grant number: 10/12642-9
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): February 01, 2011
• Effective date (End): February 01, 2015
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Janete Aparecida Anselmo Franci
• Grantee: Bruna Kalil Cutti
• Host Institution: Faculdade de Odontologia de Ribeirão Preto (FORP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated scholarship(s): 13/03596-1 - Control of hypothalamic KNDy neurons during the menstrual cycle of the rhesus monkey, BE.EP.DR

Abstract

The gonadotropin-releasing hormone/luteinizing hormone (GnRH/LH) surges are triggered by the rise in estradiol plasma levels coupled to a circadian brain signal. In rodents, kisspeptin neurons in the rostral periventricular area of the third ventricle of the preoptic area (POA) are considered to provide a major stimulatory input to the GnRH neurons that are responsible for generating the GnRH/LH surge. Noradrenaline (NA) is one of the main modulators of GnRH release and NA fibers are found in close apposition to kisspeptin neurons in the RP3V. Our objective was to interrogate the role of NA signaling in the kisspeptin control of GnRH secretion during the estradiol induced LH surge in ovariectomized rats, using prazosin, an alpha-1 adrenergic receptor antagonist. In control rats the estradiol induced LH surge at 17h was associated with a significant increase in GnRH and kisspeptin content in the median eminence (ME) with the increase in kisspeptin preceding that of GnRH and LH. Prazosin, administered 5 and 3h prior to the anticipated time of the LH surge truncated the LH surge and abolished the rise in GnRH and kisspeptin in the ME. In the POA, prazosin blocked the increases in Kiss1 gene expression and kisspeptin content in association with a disruption in expression of the clock genes, Per1 and Bmal1. Together, these findings demonstrate for the first time that NA modulates kisspeptin synthesis in the RP3V through the activation of alpha-1 adrenergic receptors prior to the initiation of the LH surge and reveal a potential role of alpha-1 adrenergic signaling in the circadian-controlled pathway timing the pre-ovulatory LH surge.

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; RIBEIRO, ALINE B.; LEITE, CRISTIANE M.; UCHOA, ERNANE T.; CAROLINO, RUITHER O.; CARDOSO, THAIS S. R.; ELIAS, LUCILA L. K.; RODRIGUES, JOSE A.; PLANT, TONY M.; POLETINI, MARISTELA O.; et al. The Increase in Signaling by Kisspeptin Neurons in the Preoptic Area and Associated Changes in Clock Gene Expression That Trigger the LH Surge in Female Rats Are Dependent on the Facilitatory Action of a Noradrenaline Input. Endocrinology, v. 157, n. 1, p. 323-335, JAN 2016. (10/12642-9)