Role of relaxin in different stages of Sertoli cell development: characterization of the intracellular signaling, effects on gene and protein expression and modulation by FSH

• Grant number: 11/14262-1
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: November 01, 2011
• End date: August 31, 2015
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Maria de Fátima Magalhães Lazari
• Grantee: Aline Rosa do Nascimento
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Male fertility is controlled by a combination of hormonal signals that control the Sertoli cell production of the necessary factors for spermatogenesis. FSH and testosterone are the main regulators of spermatogenesis. Depending on the maturation stage of the Sertoli cells, these hormones activate signaling pathways such as cAMP/PKA, ERK1/2 or PI3K/AKT. Members of the PI3K/AKT and cAMP cascades activate the CREB transcription factor, which is particularly important for the maintenance of spermatogenesis. The CREB levels are especially high during the first eight stages of spermatogenesis, suggesting an important role in haploid germ cells. CREB is also responsible for the regulation of important genes for spermatogenesis, such as aromatase and inhibin. Besides testosterone and FSH, several other factors may contribute for spermatogenesis. We have recently found that relaxin, a member of the insulin-related peptide family, is present in the testis. Relaxin stimulates Sertoli cell proliferation through a mechanism that involves PI3K and ERK1/2 activation. The aim of the present study is to characterize the signaling pathways and the gene and protein expression related to cell cycle and differentiation, stimulated by relaxin in immature (from 15-day old rats) and in differentiating (from 20-day old rats) Sertoli cells. We will specifically address: 1) The effect of relaxin, under the presence or absence of FSH, on cAMP-PKA/Epac, MEK-ERK1/2 and PI3K-AKT pathways, and on the activation of the CREB transcription factor; 2) The modulation of cell cycle-related genes by relaxin using PCR array, and validating the data by qPCR, immunohistochemistry or Western blot; 3) The effect of relaxin, under the presence or absence of FSH, on the expression of genes important for spermatogenesis, such as aromatase, androgen receptor, inhibins A and B and cadherins 1 and 2.

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)

NASCIMENTO, ALINE R.; MACHERONI, CARLA; LUCAS, THAIS F. G.; PORTO, CATARINA S.; LAZARI, MARIA F. M.. Crosstalk between FSH and relaxin at the end of the proliferative stage of rat Sertoli cells. Reproduction, v. 152, n. 6, p. 613-628, DEC 2016. (10/10274-2, 14/05028-3, 14/08563-7, 11/14262-1)