Do melanin-concentrating hormone (MCH) and ghrelin interact to modulate lactation terminus?

• Grant number: 19/23577-8
• Support Opportunities: Regular Research Grants
• Start date: January 01, 2022
• End date: June 30, 2023
• Field of knowledge: Biological Sciences - Morphology - Anatomy
• Agreement: Carleton University
• Mobility Program: SPRINT - Projetos de pesquisa - Mobilidade
• Principal Investigator: Jackson Cioni Bittencourt
• Grantee: Jackson Cioni Bittencourt
• Principal researcher abroad: Alfonso Abizaid
• Institution abroad: Carleton University, Canada
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Marianne Orlandini Klein
• Associated research grant: 16/02224-1 - The existence of neurogenesis during the lactation period, AP.TEM

Abstract

Lactation is arguably the most energetically challenging state a female mammal can endure. During this time, females show physiological and behavioral changes that allow them to meet these demands as well as those of their young. These changes include increases in food intake, the catabolism of body fat, decreased energy expenditure, and the cessation of ovulation. The melanin-concentrating hormone (MCH) is synthetized in neurons in the ventromedial region of the medial preoptic area (MPOA) in the hypothalamus only in lactating females.The expression of MCH in this region peaks around 19th day postpartum, and it disappears as the pups are weaned. These data suggest that MCH may be a signal that important for the termination of lactation and the return to pre-pregnancy metabolism. Ghrelin, a stomach produced hormone, known to increase food intake and decrease energy expenditure, in the regulation of metabolism during lactation. Ghrelin acts in the hypothalamus to increase the expression of neuropeptide y (NPY) and the agouti related peptide (AGRP), both peptides that modulate food intake and metabolic rate, but also peptides that inhibit reproductive function. As such, it is possible that ghrelin plays an important role in the behavioral and metabolic changes seen during lactation. While plasma ghrelin levels are low early in lactation, the expression of the ghrelin receptor, the GHSR, is increased in the hypothalamus, especially towards the end of lactation. Additionally, both MCH and ghrelin have been implicated in the modulation of motivated behaviors, such as sexual and maternal behaviors. An important CNS area required for the expression of these behaviors is the MPOA. Ghrelin receptors are found at MPOA from adult animals, as well as MCH immunoreactive neurons are observed only in lactating females. These data combined elicit the possibility that both modulators may act together during lactation, regulating metabolic and behavioral states of the mother. Initially, we have discussed an experiment where lactating rat brains will be collected at different times across lactation, along with brains from cycling rats. In Situ hybridization for GHSR followed by immunocytochemistry for MCH will be conducted. We will to evaluate if the two co-localize and the amount of colocalization across lactation. (AU)