Recently it has been shown that leukocytes are capable of producing prolactin (PRL). Evidence of extra-pituitary PRL (ePRL) production is so far been limited to primates and is not shared across other mammal species such as mice and rats. While ePRL is characterized as an identical protein to traditional pituitary PRL, it is controlled under an alternative promoter and is thus regulated differently from pituitary PRL. Little is known about what regulates ePRL or its direct role in human physiology, but given that PRL has well over 300 described functions, it is likely that the autocrine and paracrine effects of this hormone could have far reaching implications in overall physiology. This work takes some of the first steps in understanding how leukocyte ePRL is regulated. Our results show that, adrenergic hormones are one key stimulus in ePRL expression in monocytes/macrophages. This is particularly intriguing considering the opposing role of these two signals in settings such as adipose tissue where adipose tissue macrophages are constantly exposed to pro-lipolytic adrenergic hormones that would in turn stimulate production of an anti-lipolytic hormone, PRL. Further, our work shows that the inflammatory phenotype of the leukocytes influences basal expression of PRL and overall ePRL expression increases significantly as monocytes differentiate into macrophages, as is a common occurrence in adipose tissue. The final portion of our work shows how monocytes/macrophages also respond to preadipocytes directly. These stem cell precursors to mature adipose cells release an unknown factor that stimulates ePRL production in monocytes/macrophages. Analysis of our gene array shows many of the genes stimulated by adipose stem cells alongside PRL are important genes in tissue regeneration and remodeling, a possible role that fits well with known effects of PRL. Understanding such primate specific interactions between the immune system and major metabolic tissues such as adipose fills vital gaps in knowledge that may explain why so many treatments fail when transitioning from mouse models to humans.
Doctor of Philosophy (Ph.D.)
College of Medicine
Burnett School of Biomedical Sciences
Length of Campus-only Access
Doctoral Dissertation (Open Access)
Barrett, Richard, "Regulation of Extra-Pituitary Prolactin in Monocytes and Macrophages" (2018). Electronic Theses and Dissertations, 2004-2019. 6155.