Intracellular Signaling of Melanin-Concentrating Hormone in Mammary Gland Cells of Long-Evans Rats During the Lactation Period

• Grant number: 24/22860-6
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: March 01, 2025
• End date: February 28, 2027
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Jackson Cioni Bittencourt
• Grantee: Thais Barabba Auricino
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 23/02531-5 - The melanin-concentrating hormone peptidergic system: a multiprotocolary approach to a multifunctional analysis, AP.TEM

Abstract

Melanin-concentrating hormone (MCH) is a neuropeptide that acts in several processes. Synthesized predominantly in the hypothalamus and distributed through the central nervous system [CNS], in addition to being found in other peripheral tissues as well. Its action has been well described during lactation, in regions important for maternal behavior, such as the medial preoptic area [MPOA]. Data published by our group indicate that MCH receptor 1 [MCHR1] expression fluctuated throughout the lactation period, after gestation on the 5th day (PPD5), being the beginning of lactation, and reached its maximum peak in PPD19 (late lactation) in breast tissue. The lactation process occurs under the specific hormonal influence of prolactin, which activates the Jak/Stat signaling pathway, where the mammary gland produces milk through the secretory epithelium during pregnancy. Soon after weaning, protein expression decreases along with the process of involution of the mammary gland, returning to the glandular tissue. Together, these data reinforce that MCH plays an important role in physiology during lactation. Therefore, we hypothesize that MCHR1 acts on mammary gland cells in early lactation and, as well as the opposite in late lactation. To test our hypothesis, our objective is to identify and characterize the signaling pathways of the MCHR1 peptidergic system and its role in mammary cells at different stages of lactation. It will be by obtaining a primary culture of the mammary glands at different stages of Long-Evans rats: virgins, 10th day pregnant, lactating PPD5 and PPD19, which will or will not be treated with lactogenic hormones and steroid hormones, in addition to members of the MCH family of peptides for activation from MCHR1. They will be analyzed by immunolocalization techniques, gene expression by RT-PCR, protein analysis by immunoblotting, and RNA sequencing. At the end of this project, we will better understand the still unexplored participation of MCHR1 in mammary gland cells and its importance in different stages of lactation.