Mitochondria are at the heart of the metabolic adaptations during lactation


Mitochondria are double-membrane organelles with an outer membrane and a folded inner membrane where the components of the electron transport chain (ETC) are localized. Mitochondria are considered “the powerhouses of the cell” as they generate a relatively high amount of ATP from high-energy molecules. They play crucial roles in different aspects of cellular physiology, including calcium homeostasis, metabolism, and apoptosis. Mitochondria are also essential sites for steroid hormone biosynthesis including estrogen, the main female steroid hormone. Additionally, mitochondria are also important hormone targets. Among the hormones affecting mitochondrial activity and regulating the underlying adaptations to shifting bioenergetic and metabolic requirements are estrogens, progestagens, and prolactin. With considerable increases in energy needs and variable hormone levels, lactation poses a metabolic challenge. Liver mitochondria enhance respiration linked to succinate dehydrogenase, superoxide dismutase activity, and state 3 and 4 respiration to fulfil these bioenergetic needs. In response, the respiratory control ratio and catalase activity in skeletal muscle mitochondria increase.

In a new paper published in Molecular and Cellular Endocrinology Dr. Carolina Álvarez-Delgado from the Department of Biomedical Innovation at the Ensenada Center for Scientific Research and Higher Education (CICESE) in Mexico wrote a an expert opinion review focusing on the mitochondrial adaptations that take place during lactation, a physiological condition that involves changes in metabolism and increases in energy and nutrient demand. The major goal was to explain these alterations in the context of lactation’s hormonal environment, paying particular emphasis to estrogens, progestagens, and prolactin (PRL), all of which have been shown to have an effect on mitochondrial structure and function.

Previous research has shown the importance of the biological function of estradiol (E2), progesterone (P4), and PRL they are crucial mitochondrial components, where the hormones prepare the cell for the required alterations by triggering adaptive metabolic responses in the mitochondria. The only PRL receptors (PRLRs) known as of yet are cell membrane proteins. Therefore, a combination of anterograde signals brought on by variations in P4 and E2 are likely responsible for mitochondrial adaptations to the varying PRL levels during pregnancy and breastfeeding. There are changes in the respiratory control ratio (or mitochondrial efficiency) and catalase activity in the mitochondria of skeletal muscle as well as changes in the state 3 and 4 respiration, catalase and CuZnSOD activity, lipoperoxidation, and complex II respiration in the mitochondria of the liver. According to Dr. Carolina Álvarez-Delgado, P4 levels similar to those at the start of the luteal phase and E2 concentrations similar to those found during menstruation have an impact on mitochondrial activity during lactation. This is seen as a low-hormone milieu in a physiological setting that could not be powerful enough to activate the mitochondrial steroid receptors. The author successfully reviewed recent in vivo and epidemiological data which provides clear evidence that mitochondrial adaptations are at the heart of the “metabolic reset” provided by lactation.

This important review by Dr. Carolina Álvarez-Delgado showcased the hormonal status during lactation and provided metabolic evidence that indicate that the mitochondrial steroid receptors don’t actively facilitate the mitochondrial adaptations influencing the metabolic reset really, instead are the result of the interaction between anterograde hormone signaling and the activities of nuclear and membrane hormone receptors. The report substantially increased our knowledge of how steroid hormones exert their effects on mitochondria. This will lead to major benefits by improving the ways that steroid function can be manipulated.


Álvarez-Delgado C. The role of mitochondria and mitochondrial hormone receptors on the bioenergetic adaptations to lactation. Molecular and Cellular Endocrinology. 2022 Apr 26:111661.

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