Interactions Between Prolactin, Intracellular Signaling, and Possible Implications in the Contractility and Pathophysiology of Asthma

Abstract

Prolactin (PRL) is a hormone primarily associated with lactation, but it plays various roles in both men and women. PRL belongs to the family of peptide hormones, including placental lactogen and growth hormone. Interestingly, PRL is a pleiotropic hormone affecting several physiological and pathological conditions, including fertility. Moreover, several pathophysiological roles have been associated with this hormone, including those of the immune system, autoimmune disorders, asthma, and ageing. Additionally, PRL receptors are ubiquitously expressed in tissues, including the mammary gland, gonads, liver, kidney, adrenal gland, brain, heart, lungs, pituitary gland, uterus, skeletal muscle, skin blood cells, and immune system. Therefore, in the present paper, we cover the potential role that PRL may play in asthma by promoting inflammation and modulating immune responses. The detection of its receptor in lung tissue suggests a direct role in airway smooth muscle contractility through activation of signaling pathways such as JAK2-STAT5, MAPK/ERK1/2, and PI3K/Akt, as well as influencing ionic currents that regulate cell contraction, proliferation, and survival. In this sense, this review aims to explore the potential involvement of PRL in asthma pathophysiology by examining its interactions with intracellular signaling pathways and its possible impact on airway smooth muscle contractility and immune modulation.

Keywords: PRL; asthma; contraction; hormonal regulation; prolactin.

Figure 3

PRLR domain structures obtained from the Protein Databank (https://www.rcsb.org/, accessed on 11 July 2025). (a) PRLR-ECD (ID: 1BP3) [74], (b) PRLR-TDM (ID: 2N7I) [75].

Figure 1

Proposed effects of prolactin in the lungs. Prolactin (PRL) can be synthesized either in the pituitary gland or in extrapituitary tissues, such as endothelial cells, adipocytes, the prostate, mammary glands, lungs, fibroblasts, etc. Prolactin then can be released into the blood stream to reach its target organ. In the lung, prolactin can exert immunomodulatory effects, activity over ion channels, and regulation of intracellular processes mediated by the activation of the MEK1/2/ERK1/2, JAK/STAT5, and PI3K/AKT pathways.

Figure 2

PRL structure (ID: 1RW5) obtained from the Protein Databank (https://www.rcsb.org/, accessed on 11 July 2025).

Figure 4

Top 20 PRL-PPI interactions. The figure indicates the top 20 protein-protein interactions of PRL according to the STRING database (https://string-db.org/, accessed on 1 March 2025) from Homo sapiens. On the right side of the figure, we can see the types of interactions, network properties, and enrichment analysis of the main pathways involved in the PRL network.