Disfunction of growth hormone secretion effects in the hypothalamic kisspeptin system

• Grant number: 21/08792-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: May 01, 2023
• End date: September 30, 2025
• Field of knowledge: Biological Sciences - Physiology
• Principal Investigator: Renata Frazão
• Grantee: Guilherme Andrade Alves
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The growth hormone (GH) is the most abundant hormone secreted by the anterior pituitary gland. Evidences indicates the GH involvement on reproduction. GH deficiency induces puberty delay, which may even lead to infertility. Our group has recently demonstrated that GH signaling in cells that express the Kiss1 gene modulates the expression of HPG axis essential genes, such as the gene that encodes GnRH (Gnrh1) and the gene that encodes kisspeptins (Kiss1) during puberty. Kisspeptins are considered the main modulators of the GnRH neurons activity. The kisspeptin neurons responsible for modulating GnRH cells, are located in the periventricular anteroventral/rostral nucleus (AVPV/PeN) and the arcuate nucleus of the hypothalamus (ARH). This study aims to evaluate if animals with spontaneous GH deficiency or that overexpress GH have reproductive deficits due to impairment of kisspeptin neurons. Kiss1/hrGFP, Ghrhrlit and bGH mices will be used. Sexual maturation of these animals will be determined by the evaluation of the estrous cycle, vaginal opening, first estrus, cyclicity, testicular descent and balano-preputial separation. The obtained tissues will be used to performed hypothalamic mRNA expression quantification, immunohistochemistry, quantitative analysis and electrophysiology of the Kiss1 expressing neurons. Until recently, possible actions of GH in the central nervous system had not been studied. Is still unknown if changes in GH secretion and/or signaling occur in central components of the HPG axis to modulate puberty and/or fertility. Our goal is to contribute to the understanding of factors that modulate the activity of neurons required for reproduction control.

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)

TAVARES, MARIANA R.; DOS SANTOS, WILLIAN O.; AMARAL, ANDRESSA G.; LIST, EDWARD O.; KOPCHICK, JOHN J.; ALVES, GUILHERME A.; FRAZAO, RENATA; DOS SANTOS, JESSICA D. M.; CRUZ, ALESSANDRA G.; CAMPOREZ, JOAO PAULO; et al. Growth hormone receptor in VGLUT2 or Sim1 cells regulates glycemia and insulin sensitivity. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v. 121, n. 52, p. 11-pg., 2024-12-24. (20/10102-9, 21/08792-0, 18/04956-5, 22/11262-5, 20/01318-8)